SECTION 1: GASTRIC AND ESOPHAGEAL CANCERS
CONCEPTUAL SUMMARY
Gastric Cancer Overview:
- Gastric cancer is staged and treated based on histology, location, and molecular markers. Perioperative chemotherapy with FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) has replaced ECF/ECX as the Category 1 perioperative regimen for localized gastric cancer based on the FLOT4-AIO trial showing significant improvement in overall survival. ECF and its modifications (EOX, ECX) are no longer preferred perioperative regimens.
- HER2 Testing: HER2 overexpression occurs in 20–30% of patients with gastric cancer and occurs more frequently in gastroesophageal junction (GEJ) tumors than in gastric tumors.
- NCCN recommends the addition of trastuzumab to first-line chemotherapy for HER2-positive disease.
- Based on KEYNOTE-811, pembrolizumab added to trastuzumab and chemotherapy (FOLFOX) is an appropriate first-line regimen for HER2-positive gastroesophageal cancer with PD-L1 CPS ≥ 1.
- Fam-trastuzumab deruxtecan (T-DXd) is indicated after progression on a trastuzumab-containing regimen (DESTINY-Gastric01 trial) — not in the first-line setting.
- Second-Line Gastric/GEJ Cancer:
- For HER2-positive disease — T-DXd after prior trastuzumab.
- Ramucirumab-based regimens (with or without paclitaxel) are indicated only for adenocarcinoma histologies — NOT for squamous cell carcinoma.
- Trifluridine/tipiracil is indicated after progression on 2 prior lines of therapy.
Esophageal Cancer:
For locally advanced resectable esophageal adenocarcinoma, the standard of care is neoadjuvant chemoradiation with the CROSS regimen (carboplatin + paclitaxel + radiation) — trastuzumab is NOT added in the neoadjuvant setting even for HER2-positive tumors. For esophageal squamous cell carcinoma (SCC) progressing after prior chemotherapy, nivolumab is approved regardless of PD-L1 expression (ATTRACTION-3 trial). Pembrolizumab is indicated in esophageal SCC only if PD-L1 CPS ≥ 10 (KEYNOTE-181). If the patient already received immune therapy in the front-line, do NOT repeat immune therapy — use a single-agent taxane (paclitaxel) instead.
CDH1 Mutation (Hereditary Diffuse Gastric Cancer):
Germline CDH1 mutations carry up to 70–80% lifetime risk of diffuse (signet ring cell) gastric cancer. NCCN recommends prophylactic total gastrectomy between ages 20 and 30. Surveillance EGD is an alternative for those refusing or delaying surgery but is not equivalent in efficacy.
Fluorouracil (5-FU) is associated with radiation recall. For mild radiation recall — observation and continue therapy with no modifications. Dose reduction is indicated for severe reactions. High-dose steroids and discontinuation of therapy are reserved for severe reactions affecting internal organs.
PRACTICE QUESTIONS — GASTRIC AND ESOPHAGEAL CANCERS
KW is a 56-year-old female with poorly differentiated adenocarcinoma, diffuse type with signet ring cells, located in the antrum of the stomach. PET scan is negative for metastases and exploratory laparotomy showed no peritoneal disease. She will undergo perioperative chemotherapy with surgery. Which of the following perioperative regimens is most appropriate for KW's localized gastric cancer?
A. EOX (epirubicin, oxaliplatin, capecitabine)
B. 5-FU + oxaliplatin + radiation
C. FLOT (5-FU, leucovorin, oxaliplatin, docetaxel)
D. Carboplatin + paclitaxel + radiation
Explanation: The FLOT4-AIO trial showed significant improvement in overall survival with perioperative FLOT over the ECF/ECX regimen. FLOT has replaced ECF and its modifications as the Category 1 perioperative regimen for localized gastric cancer. EOX is an ECF modification — these have been removed from perioperative regimen recommendations and are no longer the preferred choice. Options B and D include radiation, which is not appropriate as a perioperative regimen for localized gastric cancer — these regimens are more appropriate for preoperative or definitive treatment of localized or locally advanced esophageal cancer.
[/expand]FT is a 55-year-old female with newly diagnosed metastatic intestinal type GEJ adenocarcinoma. Her oncologist recommends starting first-line chemotherapy with cisplatin and capecitabine. Given the location and histology of the tumor, she may be eligible for targeted therapy in addition to chemotherapy. Screening for which of the following tumor markers should be performed in consideration of targeted therapy?
A. KRAS activating mutation
B. BRAF V600E mutation
C. HER2 expression
D. ALK fusion
Explanation:
- HER2 overexpression occurs in 20–30% of patients with gastric cancer and occurs more frequently in tumors located at the GEJ compared to the stomach. NCCN recommends the addition of trastuzumab to chemotherapy for HER2-positive disease as first-line treatment.
- KRAS activating mutations are relevant in colorectal cancer — EGFR inhibitors like cetuximab and panitumumab have not been shown to be effective in gastric and esophageal cancers, and downstream KRAS targeting has not yet shown efficacy outside early-phase trials.
- BRAF mutations and ALK alterations are very rare in gastric and esophageal cancers, and there are no approved therapies for these alterations in this setting.
FT is a 55-year-old female with newly diagnosed metastatic intestinal type GEJ adenocarcinoma. Molecular testing reveals HER2 IHC 3+ and PD-L1 CPS of 10. Her ECOG is 0. Which of the following regimens is most appropriate for first-line therapy for FT?
A. FOLFOX + nivolumab
B. FOLFOX + trastuzumab + pembrolizumab
C. Trastuzumab + pembrolizumab
D. Fam-trastuzumab deruxtecan-nxki
Answer: B. FOLFOX + trastuzumab + pembrolizumab
Explanation: Because FT is HER2-positive, trastuzumab must be added to first-line chemotherapy. Based on KEYNOTE-811, pembrolizumab added to trastuzumab and chemotherapy showed significant benefit and is appropriate for FT with HER2 IHC 3+ and CPS ≥ 1. FOLFOX + nivolumab (option A) does not contain trastuzumab — if FT were HER2-negative, this would be an appropriate regimen. Trastuzumab + pembrolizumab without chemotherapy (option C) is not an appropriate front-line regimen — FT should be able to tolerate chemotherapy. Fam-trastuzumab deruxtecan (option D) is only indicated after progression on a trastuzumab-containing regimen and is not appropriate in the first-line setting.
[/expand]FT received 12 cycles of FOLFOX + trastuzumab + pembrolizumab, then went on to maintenance trastuzumab + pembrolizumab. Scans today show progression in her liver. FT would like to continue to receive treatment. Which of the following regimens is most appropriate for second-line treatment of FT?
A. ECF (epirubicin, cisplatin, 5-FU) + trastuzumab
B. Fam-trastuzumab deruxtecan
C. Nivolumab
D. Trifluridine/tipiracil
Explanation: The DESTINY-Gastric01 trial showed efficacy of fam-trastuzumab deruxtecan in the subsequent-line setting for HER2-positive upper GI cancers — this is an appropriate option for FT after progression on a trastuzumab-containing regimen. ECF (option A) is a three-drug chemotherapy regimen — these are not used in the subsequent-line setting, and continuation of trastuzumab in upper GI cancers has not shown benefit. Nivolumab (option C) is only indicated for squamous cell carcinomas in the subsequent-line setting — not for adenocarcinomas. Trifluridine/tipiracil (option D) is indicated after progression on 2 prior lines of therapy — FT has only progressed on one line.
[/expand]GM is a 60-year-old male with metastatic esophageal squamous cell carcinoma who received first-line FOLFOX for 10 cycles. CT scans reveal progression in the primary tumor and liver metastases. NGS reveals microsatellite stable disease and PD-L1 CPS of 2. Which of the following regimens is most appropriate for second-line treatment of GM's metastatic esophageal squamous cell carcinoma?
A. ECF (epirubicin, cisplatin, 5-FU)
B. Pembrolizumab
C. Ramucirumab + paclitaxel
D. Nivolumab
Explanation: The ATTRACTION-3 trial demonstrated significant OS improvement with nivolumab over chemotherapy in patients with unresectable or metastatic esophageal SCC refractory or intolerant to one prior fluoropyrimidine-based and platinum-based chemotherapy. Nivolumab has FDA approval in this setting regardless of PD-L1 expression. ECF (option A) is a three-drug chemotherapy regimen — not used in the subsequent-line setting. Pembrolizumab (option B) is indicated for second-line treatment in esophageal SCC only if the tumor is MSI-H or has a PD-L1 CPS ≥ 10 — GM's CPS of 2 does not meet this threshold. Ramucirumab-based regimens (option C) are indicated only for adenocarcinoma histologies — not for SCC.
[/expand]GM is a 60-year-old male with metastatic esophageal squamous cell carcinoma with PD-L1 CPS of 25. He received first-line FOLFOX + nivolumab for 10 cycles. CT scans reveal progression in the primary tumor and liver metastases. Which of the following regimens is most appropriate for second-line treatment of GM's metastatic esophageal squamous cell carcinoma?
A. ECF (epirubicin, cisplatin, 5-FU)
B. Pembrolizumab
C. Ramucirumab + paclitaxel
D. Paclitaxel
Explanation: Because GM received immune therapy (nivolumab) in the front-line setting, it is NOT appropriate to continue or switch to another immune therapy agent in the subsequent-line setting — his disease has already progressed on immunotherapy. A single-agent taxane such as paclitaxel is an appropriate subsequent-line therapy after prior immunotherapy progression. ECF (option A) is a three-drug chemotherapy regimen — not used in the subsequent-line setting. Pembrolizumab (option B) is inappropriate because GM already progressed on immune therapy in the front-line setting. Ramucirumab-based regimens (option C) are indicated only for adenocarcinoma histologies — not for SCC.
[/expand]HT is a 58-year-old female with locally advanced esophageal adenocarcinoma who received preoperative chemoradiation with carboplatin and paclitaxel followed by esophagectomy. She was later found to have new liver metastases and received cycle 1 of FOLFIRI. She presents today for pump disconnection and reports that the skin on her chest is red and painful to touch. The physician is concerned she may be experiencing mild radiation recall. Which of the following management strategies is most appropriate for HT's mild radiation recall?
A. Observation and continue therapy with no modifications
B. Supportive care and continue therapy with dose reduction
C. Steroid premedication and continue therapy with dose reduction
D. High-dose steroids and discontinue therapy
Explanation: Fluorouracil (5-FU) is a chemotherapy agent known to be associated with radiation recall. Symptoms can occur during or immediately after intravenous infusions, consistent with the timing described. For MILD radiation recall, it is reasonable to continue receiving chemotherapy with close monitoring. The affected area should be kept clean and dry. Supportive care measures such as moisturizers, NSAIDs, antihistamines, or topical steroids may be considered if needed. Dose reduction (options B and C) is indicated for severe skin reactions. High-dose steroids and discontinuation (option D) are reserved for severe reactions or reactions affecting internal organs.
[/expand]A 30-year-old man with no significant past medical history undergoes multigene panel testing based on his family history and is found to have a germline truncating mutation in CDH1. In addition to routine age-appropriate screening, which of the following would you also recommend to the patient?
A. CT abdomen/pelvis yearly
B. Check carcinoembryonic tumor marker and then follow every 3 months
C. Diagnostic laparoscopy
D. Prophylactic gastrectomy
E. Surveillance EGD at age 35 and then every 5 years
Explanation: A germline pathogenic mutation in the CDH1 gene is associated with Hereditary Diffuse Gastric Cancer (HDGC) syndrome, which carries a very high lifetime risk (up to 70–80%) of developing diffuse (signet ring cell) gastric cancer. Because this cancer is often insidious and not reliably detected by endoscopy, current NCCN guidelines recommend discussing the option of prophylactic total gastrectomy between the ages of 20 and 30. Intensified endoscopic surveillance (option E) is an alternative for those refusing or delaying surgery, but it is not considered equivalent in efficacy due to the high rate of occult cancer and the limitations of endoscopy in detecting diffuse lesions. CT abdomen/pelvis, CEA monitoring, and diagnostic laparoscopy are not standard management for this genetic condition.
[/expand]A 45-year-old man with GERD presented with worsening dysphagia. Upper endoscopy reveals a 3 cm distal esophageal mass. Biopsy shows esophageal adenocarcinoma with HER2 overexpression invading the adventitia. PET/CT demonstrates distal esophageal uptake with several suspicious local lymph nodes. The patient is agreeable to aggressive treatment including surgery if needed. What is the best initial treatment for this patient?
A. Neoadjuvant chemoradiation with carboplatin and paclitaxel
B. Neoadjuvant chemoradiation with carboplatin, paclitaxel, and trastuzumab
C. Perioperative chemotherapy with epirubicin, cisplatin, and fluorouracil
D. Fluorouracil, oxaliplatin, and nivolumab
Explanation: This patient has locally advanced (T3N1M0) resectable esophageal adenocarcinoma. The standard of care is neoadjuvant chemoradiation followed by surgery using the CROSS trial regimen — carboplatin and paclitaxel with concurrent radiotherapy. Although the tumor is HER2-positive, the addition of trastuzumab (option B) is NOT part of the standard neoadjuvant regimen for localized disease — its role is established in first-line treatment for metastatic HER2-positive gastroesophageal cancer. ECF perioperative chemotherapy (option C) is an older, less preferred regimen; FLOT-based perioperative chemotherapy is an alternative option for GEJ tumors, but chemoradiation with CROSS is often preferred for esophageal tumors. Nivolumab (option D) is used in metastatic or adjuvant settings — not as initial neoadjuvant therapy for localized disease.
[/expand]Which of the following is the best treatment option for a 60-year-old man with esophageal squamous cell carcinoma after prior definitive chemoradiation and 5-FU/oxaliplatin for recurrent disease, who now presents with disease progression and PD-L1 CPS of 1?
A. Nivolumab
B. Trifluridine/tipiracil
C. Pembrolizumab
D. Ramucirumab
Explanation: Nivolumab is approved for advanced or metastatic esophageal squamous cell carcinoma after prior chemotherapy regardless of PD-L1 expression. The ATTRACTION-3 trial demonstrated improved overall survival compared to chemotherapy in previously treated patients. Pembrolizumab (option C) is typically reserved for patients with PD-L1 CPS ≥ 10 in esophageal SCC based on KEYNOTE-181 data — this patient's CPS of 1 does not meet the threshold. Trifluridine/tipiracil (option B) is approved for metastatic gastric or GEJ adenocarcinoma, not squamous cell carcinoma of the esophagus. Ramucirumab (option D) is used in combination with paclitaxel for gastric or GEJ adenocarcinoma — not squamous histology.
[/expand]A 55-year-old man with metastatic gastric cancer (HER2/neu-negative) was treated with 4 months of FOLFOX. Imaging shows disease progression. He has otherwise tolerated therapy well. Which of the following are options for second-line management of this patient?
A. Ramucirumab + paclitaxel
B. Ramucirumab alone
C. Paclitaxel alone
D. Irinotecan-based therapy
E. All of the above
Explanation: In HER2-negative metastatic gastric cancer that has progressed on first-line platinum/fluoropyrimidine-based therapy, multiple validated second-line options exist. The RAINBOW trial established ramucirumab + paclitaxel as a standard second-line regimen showing a significant survival benefit (option A). The REGARD trial showed a survival benefit for ramucirumab as a single agent compared to placebo (option B). Single-agent chemotherapy with paclitaxel or docetaxel is also an acceptable option (option C). Irinotecan-based therapy is another recognized second-line chemotherapy option (option D). Therefore, all listed choices are potential options for second-line management.
[/expand]SECTION 2: HEPATOCELLULAR CARCINOMA (HCC)
CONCEPTUAL SUMMARY
Definition: HCC is the most common primary liver cancer (approximately 75–85% of all primary liver cancers), typically arising in the setting of chronic liver disease and cirrhosis.
Risk Factors: Chronic viral hepatitis (HBV, HCV), alcohol-related liver disease, NAFLD/NASH, aflatoxin B1 exposure, and genetic/metabolic disorders (hemochromatosis, α1-antitrypsin deficiency, Wilson's disease).
Staging: HCC is commonly staged using the BCLC (Barcelona Clinic Liver Cancer) system, which considers tumor burden, liver function (Child-Pugh classification), and performance status. The Milan criteria for liver transplantation require either a single tumor ≤ 5 cm or up to 3 tumors each ≤ 3 cm.
HCC Screening: Patients with Child-Pugh class A or B cirrhosis are recommended for routine HCC surveillance — typically liver ultrasound and/or AFP testing every 6 months. Child-Pugh class C patients are NOT recommended for surveillance unless they are on the liver transplantation waiting list, as surveillance does not improve survival if transplant will not be pursued. NAFLD without cirrhosis is not high-risk — widespread screening is not recommended.
Treatment Overview:
- Curative options (early-stage): surgical resection, liver transplantation (within Milan criteria), and ablation (RFA, microwave).
- Locoregional (intermediate stage): TACE (transarterial chemoembolization) or TARE (transarterial radioembolization) — indicated for large unresectable tumors without extrahepatic spread when the patient is not a transplant or resection candidate.
- Systemic therapy (advanced/unresectable):
- First-line preferred: atezolizumab + bevacizumab (IMbrave150 trial — median OS not reached vs 13.2 months with sorafenib; bevacizumab requires endoscopic screening for varices before initiation). First-line alternatives: durvalumab ± tremelimumab (STRIDE regimen), lenvatinib, sorafenib.
- Second-line: regorafenib, cabozantinib, nivolumab, pembrolizumab (selected patients), ramucirumab (if AFP ≥ 400 ng/mL).
Pharmacist Considerations: Monitor liver function for all agents. TKIs (sorafenib, lenvatinib, regorafenib, cabozantinib) — toxicities include hand-foot syndrome, diarrhea, hypertension, and hepatotoxicity. Bevacizumab — monitor for bleeding, hypertension, proteinuria; contraindicated in patients with untreated varices with bleeding risk. All TKIs have CYP3A4 drug interactions.
PRACTICE QUESTIONS — HEPATOCELLULAR CARCINOMA
JP is a 53-year-old male with a history of hepatitis B infection. AFP is 1,405 ng/mL. CT scan reveals a liver mass in the right lobe measuring 5.5 × 5.3 cm consistent with locally advanced, unresectable HCC. He is Child-Pugh class A6. Which treatment option will offer JP the best overall survival for his unresectable HCC?
A. Liver transplantation
B. FOLFOX
C. Atezolizumab + bevacizumab
D. Sorafenib
Explanation: In the IMbrave150 trial, atezolizumab + bevacizumab was compared against sorafenib in previously untreated patients with unresectable HCC. Median OS had not been reached in the combination group versus only 13.2 months in the sorafenib group, and PFS was significantly improved. This combination is the current preferred first-line standard of care for unresectable HCC. Liver transplantation (option A) is incorrect because JP's tumor measures 5.5 cm — exceeding the Milan criteria threshold for transplant eligibility (single tumor ≤ 5 cm). FOLFOX (option B) has not been shown to improve OS in HCC — it is only an option for patients who cannot tolerate TKI or anti-angiogenic agents. Sorafenib (option D) was the previous standard of care but has been superseded by atezolizumab + bevacizumab based on the IMbrave150 survival advantage.
[/expand]Which of the following patients would benefit from HCC screening?
A. Nonalcoholic fatty liver disease without cirrhosis
B. History of chronic hepatitis C with Child-Pugh class A cirrhosis
C. Chronic hepatitis B with Child-Pugh class C cirrhosis not a candidate for liver transplantation
D. B and C
E. All of the above
Explanation: Patients with Child-Pugh class A or B cirrhosis are recommended for routine HCC surveillance — typically liver ultrasound and/or AFP testing every 6 months — because surveillance in these patients can lead to early detection and improved survival. Patients with Child-Pugh class C cirrhosis (option C) are NOT recommended for HCC surveillance unless they are on the liver transplantation waiting list — surveillance does not improve survival in this group if transplant will not be pursued. NAFLD without cirrhosis (option A) is not considered high-risk for HCC, and widespread screening is not recommended in this population. Therefore, only option B is the correct answer.
[/expand]A 48-year-old male presents for discussion of treatment options for his HCC. A 6.0 cm tumor in segment 4b consistent with HCC was seen on triple-phase CT. His platelet count is 88 and bilirubin is 1.1. He is otherwise in good health with ECOG of 0. What is the most appropriate treatment recommendation?
A. Liver transplantation
B. Local-regional therapy (TACE or TARE)
C. Systemic therapy
D. Surgical resection
E. Supportive care
Explanation: The key to HCC management is assessing tumor stage and underlying liver function. Surgical resection (option D) requires adequate liver function and absence of portal hypertension — this patient's low platelet count (88,000/µL) suggests significant portal hypertension and cirrhosis, making resection high-risk due to post-operative liver decompensation. Liver transplantation (option A) is excluded because the tumor is 6.0 cm, which exceeds the Milan criteria (single tumor ≤ 5 cm or 3 tumors ≤ 3 cm). Systemic therapy (option C) and supportive care (option E) are less appropriate when the patient has a good performance status (ECOG 0) and a single large tumor confined to the liver — more aggressive local therapy is preferred. Local-regional therapy (option B) — TACE or TARE — is the standard of care for large unresectable tumors in patients without extrahepatic spread who are not candidates for resection or transplantation, corresponding to BCLC Stage B.
[/expand]SECTION 3: COLORECTAL CANCER (CRC)
CONCEPTUAL SUMMARY
Epidemiology and Risk Factors:
Most common sites are the sigmoid colon, rectum, and ascending colon. Risk factors include age > 50, family history, Lynch syndrome, FAP, IBD (ulcerative colitis, Crohn's), red/processed meat, obesity, alcohol, smoking, and low fiber diet.
Pathophysiology: The adenoma-carcinoma sequence involves APC mutation → KRAS mutation → TP53 mutation. Microsatellite instability (MSI) results from mismatch repair (MMR) deficiency. Chromosomal instability (CIN) is common in sporadic CRC.
Molecular Classification:
- KRAS/NRAS mutations (~40%) predict lack of response to anti-EGFR therapy — cetuximab and panitumumab must NOT be used in RAS-mutated tumors.
- BRAF V600E mutation (5–10%) indicates poor prognosis.
- dMMR/MSI-H (~15% early-stage) means immunotherapy-sensitive; these tumors also have poor response to 5-FU monotherapy.
- HER2 amplification (< 5%) has potential for anti-HER2 therapy in metastatic disease.
Clinical Presentation: Left-sided (rectum/sigmoid): hematochezia, altered bowel habits, obstruction. Right-sided (ascending colon): anemia, fatigue, occult bleeding.
Treatment by Stage:
- Stage I: surgery alone.
- Stage II: surgery ± adjuvant single-agent fluoropyrimidine (capecitabine or 5-FU/LV) for high-risk features — oxaliplatin does NOT improve survival in stage II and may not provide the same benefit in patients > 70 years. dMMR Stage II may not benefit from 5-FU monotherapy — observation may be appropriate.
- Stage III: surgery + adjuvant FOLFOX (6 months standard) or CAPOX. Per IDEA trial, CAPOX × 3 months is appropriate for high-risk stage III colon cancer; FOLFOX × 3 months was inferior to 6 months.
- FOLFIRI is NOT used in the adjuvant setting. Biologics (bevacizumab, cetuximab) are NOT recommended in the adjuvant setting. Stage IV resectable: surgery ± perioperative chemo with curative intent. Stage IV unresectable: systemic chemo ± biologics.
Biologic Selection:
- KRAS/NRAS WT + left-sided tumor: preferred anti-EGFR therapy (cetuximab or panitumumab).
- KRAS/NRAS WT + right-sided tumor: better response to chemo + bevacizumab. Bevacizumab is CONTRAINDICATED in patients with arterial thrombotic events within the last 6 months. IBD is a CONTRAINDICATION to EGFR inhibitors due to risk of severe GI toxicity (colitis). Continuing bevacizumab beyond progression (with change in chemotherapy backbone from FOLFOX → FOLFIRI) is supported by clinical trial data.
Rectal Cancer:
For T3/T4 or node-positive rectal cancer: total neoadjuvant therapy (TNT) = long-course chemoradiation (capecitabine or 5-FU, NO oxaliplatin added to radiation) → FOLFOX → surgery. Oxaliplatin added to radiation increases toxicity without improving outcomes.
DPYD Testing: One normal + one no-function allele = 50% dose reduction of 5-FU. Two no-function alleles = avoid 5-FU completely. Two normal alleles = normal dose.
Colonoscopy Surveillance: Post-resection: colonoscopy at 1 year, then 3 years, then every 5 years. Family history of CRC in first-degree relative: begin colonoscopy at age 40 or 10 years before the youngest affected relative's diagnosis (whichever comes first), every 5 years. Lynch syndrome (hereditary): more frequent intervals (1–2 years).
Key Drug Toxicities:
- Oxaliplatin: cumulative sensory neuropathy (dose-limiting), cold-induced acute neurotoxicity (avoid cold drinks/ice for 3–5 days post-infusion to prevent laryngospasm and dysphagia), NOT nephrotoxicity.
- Irinotecan:
- ACUTE diarrhea = cholinergic reaction (diaphoresis, cramping) → treat with ATROPINE (NOT loperamide); premedicate with atropine for future cycles if recurs.
- DELAYED diarrhea = treat with loperamide 4 mg loading, then 2 mg after each loose stool up to 16 mg/day.
- Bevacizumab: hypertension, proteinuria, GI perforation, bleeding — NOT thrombosis risk.
- Cetuximab/Panitumumab: acneiform (papulopustular) rash, hypomagnesemia. Grade 2 rash management: continue at same dose + topical steroids (hydrocortisone) + oral tetracycline. Salicylic acid should NEVER be used for EGFR inhibitor rash. Grade 3/4 rash: dose reduce.
- Capecitabine/5-FU: hand-foot syndrome (HFS). Grade 2/3 HFS: HOLD chemotherapy until recovery to grade 0–1 + urea 20% cream BID + clobetasol 0.05% cream daily + pain control (NSAIDs, GABA agonists, opioids).
Anal Cancer:
Chemoradiation with 5-FU + mitomycin (or capecitabine in place of 5-FU) is the preferred first-line treatment for localized anal SCC. Abdominoperineal resection (APR) is NOT first-line for anal cancer. 5-FU + cisplatin is Category 2B — non-superior and associated with increased colostomies compared to 5-FU + mitomycin.
PRACTICE QUESTIONS — COLORECTAL CANCER
LS is a 73-year-old female who underwent laparoscopic right colectomy for colon cancer. Pathology revealed moderately differentiated adenocarcinoma, negative margins, 0/29 lymph nodes positive, perineural invasion, no lymphovascular invasion, and microsatellite low. She was staged with T4a N0 M0 — high-risk stage IIB colon cancer. Which of the following is the most appropriate adjuvant therapy for LS's high-risk stage IIB colon cancer?
A. Observation
B. Capecitabine
C. FOLFOX
D. FOLFIRI
Explanation: Patients with stage II disease with high-risk features are recommended to receive adjuvant chemotherapy with a single-agent fluoropyrimidine (capecitabine or 5-FU/leucovorin). Patients with stage II disease without high-risk features or with MSI-high disease would be eligible for observation. FOLFOX (option C) is not the most appropriate adjuvant therapy for stage II disease — oxaliplatin added to a fluoropyrimidine has not been shown to improve survival benefit for stage II patients; furthermore, oxaliplatin may not provide the same benefit in patients over 70 years of age. FOLFIRI (option D) — irinotecan-containing regimens have not been shown to provide survival benefit in the adjuvant setting for early-stage disease. Observation (option A) is incorrect because LS has high-risk features (T4a, perineural invasion, microsatellite low) and no contraindications to chemotherapy.
[/expand]EH is a 65-year-old male with metastatic colorectal cancer and bilobular liver lesions. NGS shows KRAS G12C mutation, TP53 Y107* mutation, microsatellite stable, TMB 8 mutations/megabase. ECOG 1 and controlled hypertension on amlodipine. Which of the following is the most appropriate initial therapy for EH's metastatic colorectal cancer?
A. Capecitabine
B. FOLFOX + cetuximab
C. FOLFIRI + bevacizumab
D. FOLFOXIRI + panitumumab
Explanation: FOLFIRI ± bevacizumab is an acceptable option for first-line treatment of metastatic CRC in patients eligible for intensive therapy. Controlled hypertension is not a contraindication to bevacizumab. FOLFOX + cetuximab (option B) and FOLFOXIRI + panitumumab (option D) are both incorrect because EH has a KRAS G12C activating mutation, which confers resistance to EGFR monoclonal antibodies — cetuximab and panitumumab cannot be used in RAS-mutated tumors. Additionally, FOLFOXIRI only has evidence-based support in combination with bevacizumab, not with EGFR inhibitors. Capecitabine alone (option A) would only be appropriate if EH was not eligible for intensive therapy.
[/expand]EH agreed to receive FOLFIRI + bevacizumab and presents today to begin treatment. He requests further education about the diarrhea he might experience. What is the most appropriate counseling information regarding irinotecan-induced diarrhea?
A. EH will be pre-medicated with loperamide to prevent acute diarrhea
B. Acute diarrhea may be accompanied by sweating which is treated with atropine
C. EH will be given octreotide injections to prevent delayed diarrhea from the start
D. Delayed diarrhea will only occur if EH experiences acute diarrhea
Explanation: Acute irinotecan-associated diarrhea is a cholinergic reaction, often accompanied by cholinergic symptoms such as diaphoresis (sweating) and significant abdominal cramping. Atropine (or other anticholinergic agents) is the most appropriate treatment to alleviate acute irinotecan-induced diarrhea. Loperamide (option A) will not alleviate the cholinergic reaction of acute irinotecan diarrhea — loperamide is used for delayed diarrhea. Octreotide (option C) should only be considered for complicated delayed diarrhea or diarrhea refractory to loperamide — not as a pre-emptive treatment. There is no association between the occurrence of acute and delayed irinotecan-induced diarrhea (option D) — they are caused by different mechanisms.
[/expand]EH agreed to receive FOLFIRI + bevacizumab. During the irinotecan infusion, he experiences abdominal cramping and diaphoresis, along with an episode of diarrhea. What is the most appropriate intervention to alleviate EH's symptoms?
A. Give atropine, and consider pre-medication with atropine for future cycles
B. Give loperamide, and counsel EH to take loperamide around the clock at home
C. Give octreotide, and consider pre-medication with octreotide for future cycles
D. Give tincture of opium, and counsel EH to take tincture of opium around the clock at home
Explanation: Acute irinotecan-associated diarrhea is a cholinergic reaction — atropine is the most appropriate treatment to alleviate EH's symptoms. Pre-medication with atropine for future cycles should be considered if the patient experienced acute cholinergic symptoms. Loperamide (option B) will not alleviate the cholinergic reaction — it is used for delayed diarrhea. Octreotide (option C) is not appropriate for acute cholinergic diarrhea — it is reserved for complicated or loperamide-refractory delayed diarrhea. Tincture of opium (option D) can be considered for persistent uncomplicated delayed diarrhea — not for acute cholinergic reactions.
[/expand]RL is a 64-year-old female with metastatic KRAS-wild-type colorectal cancer. She recently started FOLFOX + panitumumab and presents for Cycle 3. She reports a new rash that is pruritic, occasionally weeps pus, and extends over her face and chest. She has been compliant taking doxycycline since she started treatment. What is the most appropriate intervention for RL's grade 2 papulopustular rash at this time?
A. Continue panitumumab at same dose and change doxycycline to minocycline
B. Continue panitumumab at same dose and initiate topical hydrocortisone
C. Dose reduce panitumumab and initiate topical salicylic acid
D. Dose reduce panitumumab and initiate oral prednisone
Explanation: For a Grade 2 papulopustular rash from EGFR inhibitor therapy, the most appropriate management is to continue panitumumab at the same dose and initiate topical steroids (hydrocortisone) in addition to the oral tetracycline (doxycycline) already being taken. Changing doxycycline to minocycline (option A) is incorrect — there is no evidence minocycline is more effective than doxycycline for EGFR inhibitor-associated rash; panitumumab can continue at the same dose. Dose reduction (options C and D) would be appropriate only for grade 3 or grade 4 rash. Salicylic acid (option C) should NEVER be used for EGFR inhibitor-associated papulopustular rash. Oral prednisone (option D) is appropriate for grade 3 or 4 rash — not grade 2.
[/expand]VP is a 64-year-old female with HIV on HAART therapy who presents with a squamous cell carcinoma 3 cm from the anal verge. She has no evidence of metastatic disease. Which of the following treatment options is most appropriate for VP's localized anal cancer?
A. Abdominoperineal resection with permanent colostomy
B. Radiation alone
C. Chemoradiation with 5-FU and mitomycin
D. Chemoradiation with 5-FU and cisplatin
Explanation: Chemoradiation with 5-FU and mitomycin (or capecitabine in place of 5-FU) is the preferred first-line treatment for localized anal cancer. Abdominoperineal resection (option A) is not recommended for first-line therapy of anal cancer due to long-term morbidity complications and high local recurrence rates. Radiation alone (option B) is not appropriate — the addition of chemotherapy to radiation has been shown to improve complete remission rates, reduce locoregional recurrence, and decrease the risk of requiring a colostomy. Chemoradiation with 5-FU and cisplatin (option D) has been shown to have non-superior outcomes and increased colostomies compared to 5-FU and mitomycin — it is only a Category 2B recommendation from NCCN.
[/expand]LS is a 62-year-old patient presenting to the oncologist to discuss adjuvant treatment for her stage III colon cancer. Her tumor is poorly differentiated with perineural invasion — high risk for recurrence. Medical history includes controlled hypertension. She lives 3 hours from the cancer center in a rural area with limited services. Which of the following is the most appropriate adjuvant therapy for LS's high-risk stage III colon cancer?
A. CAPEOX × 3 months
B. FOLFOX × 3 months
C. FOLFIRI × 6 months
D. Capecitabine × 6 months
Explanation: Based on the results of the IDEA trial, CAPEOX × 3 months is an appropriate adjuvant regimen for high-risk stage III colon cancer. CAPEOX × 3 months is particularly practical for LS given her rural location and distance from the cancer center — capecitabine is an oral agent that eliminates the need for frequent IV infusion visits. FOLFOX × 3 months (option B) was inferior to 6 months of FOLFOX in the IDEA trial and is therefore not recommended as a 3-month option. FOLFIRI (option C) is not currently recommended for adjuvant treatment of colon cancer. Capecitabine for 6 months alone (option D) is an alternative option, but LS has no contraindications to oxaliplatin and should receive an oxaliplatin-based regimen.
[/expand]A 35-year-old man admitted with melena was found to have a single tumor in the right colon. CT scans were negative for metastatic disease and he underwent complete surgical resection — pathologic stage T3N0 (0/15 lymph nodes). The tumor was MMR intact and MSI stable. Based on these findings, how would you counsel the patient regarding follow-up testing?
A. Counsel the patient that he has Lynch syndrome since his tumor is MMR intact and his family members should seek genetic testing
B. Instruct him to have his next colonoscopy in 5 years
C. Recommend that the patient's family members start colon cancer screening when they reach his current age (35 years old)
D. Recommend that the patient be referred to genetic counselling for extended testing for heritable causes of colon cancer
Answer: B. Instruct him to have his next colonoscopy in 5 years
Explanation: The tumor is MMR intact and MSI stable, which effectively rules out Lynch syndrome (characterized by MMR deficiency and MSI-H). Therefore, options A, C, and D are all incorrect — there is no indication for Lynch syndrome genetic counseling. This patient has stage II (T3N0) colon cancer. Standard post-resection surveillance includes a colonoscopy in 1 year post-surgery. If that is normal or shows only small adenomas, the next colonoscopy is in 3 years, and then every 5 years if normal. Option B correctly identifies the long-term follow-up interval (every 5 years) after the initial 1-year scope.
[/expand]PH is a 56-year-old man diagnosed with stage III colon cancer. After colectomy, he is planned for 6 cycles of FOLFOX. He underwent DPYD testing and was found to have 1 normal function allele and 1 no-function allele. Which of the following is recommended regarding his 5-FU dosing?
A. Start normal dose (2400 mg/m²)
B. Do 50% dose reduction (1200 mg/m²)
C. Do 75% dose reduction (600 mg/m²)
D. Do not start 5-FU
Answer: B. Do 50% dose reduction (1200 mg/m²)
Explanation: The DPYD gene encodes dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in fluoropyrimidine (5-FU, capecitabine) metabolism. One normal function allele plus one no-function allele (heterozygous variant) results in intermediate DPD activity. Guidelines recommend a 50% dose reduction followed by careful dose titration based on tolerance. Two normal alleles: normal dose. Two no-function alleles: avoid 5-FU/capecitabine completely due to high risk of severe, life-threatening toxicity. A 50% dose reduction to 1200 mg/m² is the appropriate starting dose for this patient.
[/expand]Which of the following is correct regarding colon cancer prevention?
A. Celecoxib proved to decrease risk but not used due to CVS toxicity
B. Fibers and selenium are recommended for prevention
C. Aspirin is recommended for age 50 and older who have high CV risk
D. Smoking has no effect on colon cancer risk
Explanation: COX-2 inhibitors like celecoxib have been shown to significantly reduce the risk of colorectal adenomas and cancer. However, their use for chemoprevention is limited due to the associated increased risk of major cardiovascular events (heart attack, stroke). A high-fiber diet may be associated with lower CRC risk, but it is not formally recommended as a specific preventive supplement — selenium has not been proven to prevent CRC and may be harmful in some studies (option B is incorrect). Aspirin is considered for patients with high CRC risk (e.g., strong family history, personal history of adenomas) based on a careful risk-benefit analysis of bleeding versus cancer prevention — not specifically for those with high CV risk (option C is incorrect). Smoking is a well-established risk factor for colorectal cancer (option D is incorrect).
[/expand]LA is a 30-year-old man whose father was diagnosed with CRC at age 45 and whose uncle was diagnosed at age 50. He came to ask about screening. Which of the following is correct?
A. He should start colonoscopy at 40 years old then every 1–2 years
B. He should start colonoscopy at 35 years old then every 1–2 years
C. He should start colonoscopy at 40 years old then every 5–10 years
D. He should start colonoscopy at 35 years old then every 5–10 years
Explanation: For individuals with a first-degree relative diagnosed with colorectal cancer, screening should begin at age 40 or 10 years earlier than the youngest diagnosis, whichever comes first. LA's father was diagnosed at 45 — so 10 years earlier would be 35 years old. Screening should continue every 5 years for increased-risk individuals. More frequent 1–2 year intervals are reserved for hereditary syndromes such as Lynch syndrome, which require genetic confirmation and a stronger family history pattern. Starting at age 40 (options A and C) is too late when there is a first-degree family history with the earliest diagnosis at 45. The 1–2 year interval (option B) is too frequent for most family-history cases without confirmed hereditary syndrome.
[/expand]A 55-year-old man who recently underwent resection of a stage III colon cancer presents to discuss the next step in his care. His tumor expresses mismatch repair proteins. What adjuvant therapy would you recommend for him?
A. FOLFIRI
B. FOLFOX
C. FOLFOX + bevacizumab
D. FOLFOX + cetuximab
Explanation: The standard of care for adjuvant therapy in stage III colon cancer is FOLFOX (or CAPOX). This is based on proven survival benefits. FOLFIRI (option A) is used in the metastatic setting — not in the adjuvant setting for colon cancer. The addition of biologic agents — bevacizumab (option C) or cetuximab (option D) — to adjuvant chemotherapy has NOT shown benefit in the adjuvant setting for colon cancer and is not recommended. The tumor expressing mismatch repair proteins means it is microsatellite stable (MSS) — the most common phenotype. This does not change the recommendation since for stage III disease, FOLFOX is indicated regardless of MMR status.
[/expand]A 65-year-old woman has newly diagnosed adenocarcinoma of the distal rectum with MRI showing tumor invasion of the bladder wall and no lymphadenopathy. CT chest, abdomen, and pelvis are negative for metastatic disease. She lives alone and regularly walks 2 miles three times per week. How should her disease be treated?
A. Capecitabine chemoradiation, followed by FOLFOX, followed by surgery
B. Capecitabine and oxaliplatin chemoradiation, followed by FOLFOX, followed by surgery
C. Capecitabine chemoradiation followed by surgery
D. Capecitabine and oxaliplatin chemoradiation followed by surgery
Explanation: This patient has locally advanced rectal cancer (T4b due to bladder invasion, N0, M0). The standard of care is total neoadjuvant therapy (TNT) which includes long-course chemoradiation with a radiosensitizer (capecitabine or 5-FU — NOT oxaliplatin) as the first step, followed by a course of multi-agent systemic chemotherapy (FOLFOX) to treat potential micrometastases, then surgical resection. Oxaliplatin (options B and D) is NOT added to radiation — it increases toxicity without improving outcomes. Option C omits the crucial systemic chemotherapy (FOLFOX) component, which is essential in the TNT approach for locally advanced disease. Option A correctly sequences all three components: chemoradiation → FOLFOX → surgery.
[/expand]A 60-year-old man with newly diagnosed metastatic adenocarcinoma of the sigmoid colon with lung and liver metastases has MMR-proficient disease that is KRAS, NRAS, and BRAF wild-type. He had a myocardial infarction 2 months ago and an ischemic stroke approximately 2 years ago without residual deficits. He exercises three times a week and works full time. What regimen is most appropriate as first-line therapy?
A. FOLFOX + bevacizumab
B. FOLFOX + cetuximab
C. FOLFIRI
D. Regorafenib
Explanation: The tumor is RAS and BRAF wild-type, making it eligible for EGFR inhibitors (cetuximab or panitumumab). The critical factor here is his recent cardiovascular history — bevacizumab (an anti-VEGF agent) is contraindicated in patients with a recent arterial thrombotic event (MI within the last 6 months) due to significantly increased risk of another event. His MI was 2 months ago, making bevacizumab unsafe. Cetuximab (an anti-EGFR agent) does not carry this same cardiovascular risk and is the appropriate biologic to combine with FOLFOX as first-line therapy. FOLFIRI alone (option C) is a valid chemotherapy option but omits a biologic agent which improves outcomes in fit first-line patients. Regorafenib (option D) is a later-line therapy used after failure of standard chemotherapy regimens.
[/expand]EN is a 54-year-old man with stage IV colon cancer, KRAS WT. After 8 cycles of FOLFOX + bevacizumab he was found to have progressive disease. His PS is 1 and comorbidities include IBD and DM type 2, both controlled with medications. Which of the following is recommended as subsequent therapy for him?
A. Panitumumab
B. FOLFIRI
C. Continue bevacizumab and start FOLFIRI
D. Irinotecan
Explanation: EN has progressive disease on first-line FOLFOX + bevacizumab. The standard approach for second-line therapy is to switch the chemotherapy backbone (from oxaliplatin-based FOLFOX to irinotecan-based FOLFIRI) and continue the anti-VEGF agent (bevacizumab). Panitumumab (option A) is an EGFR inhibitor — while the tumor is KRAS WT, patients with IBD have a contraindication to EGFR inhibitors due to the high risk of severe gastrointestinal toxicity (diarrhea, colitis). FOLFIRI alone (option B) is a valid chemotherapy switch but omits the benefit of continuing bevacizumab. Irinotecan alone (option D) is inferior to using it in combination (FOLFIRI).
[/expand]A 63-year-old woman has adenocarcinoma in the ascending colon and a single metastatic lesion in the periphery of the right hepatic lobe measuring 3 cm. By CT criteria, both the primary tumor and regional lymph nodes are surgically resectable. The tumor expresses mismatch repair proteins and is KRAS G12d mutant. What is the next step in management?
- Synchronous resection of primary colon tumor and en bloc resection of regional lymph nodes, along with metastasectomy of liver lesion followed by 6 months of adjuvant FOLFOX
- FOLFOX + bevacizumab until disease progression or intolerance
- Neoadjuvant FOLFOX + cetuximab, followed by resection of the liver lesion and primary colon tumor
- FOLFOX + cetuximab until disease progression or intolerance
Answer: A. Synchronous resection of primary colon tumor and en bloc resection of regional lymph nodes, along with metastasectomy of liver lesion followed by 6 months of adjuvant FOLFOX
Explanation: This patient has potentially resectable metastatic CRC with a solitary liver metastasis — the goal is curative-intent surgery. The tumor is KRAS mutant (G12d), which means it is resistant to EGFR inhibitors (cetuximab, panitumumab) — options C and D containing cetuximab are immediately incorrect. Option B (palliative bevacizumab-based therapy) is for unresectable disease, not for a patient with a resectable solitary metastasis. For resectable metastatic disease, the standard approach is resection of both the primary tumor and the metastatic lesion(s) (synchronously or staged), followed by adjuvant chemotherapy (FOLFOX) to eradicate micrometastatic disease. Upfront surgery followed by FOLFOX is a valid and direct approach for straightforward resectability.
[/expand]A 70-year-old man recently underwent colectomy for his stage IV colon adenocarcinoma. He is doing well with no complaints and his last colonoscopy was just prior to his diagnosis. What follow-up should he expect in the next year?
- History and physical along with a CEA, and CT chest, abdomen, and pelvis every 3 to 6 months for 2 years then every 6 months for 5 years; and colonoscopy in 1 year then after 3 and 5 years
- Colonoscopy in 1 year
- History and physical every 6 months along with CT chest, abdomen, and pelvis
- History and physical every 3 to 6 months along with a CEA, and PET/CT every 6 months
Answer: A. History and physical along with a CEA, and CT chest, abdomen, and pelvis every 3 to 6 months for 2 years then every 6 months for 5 years; and colonoscopy in 1 year then after 3 and 5 years
Explanation: Surveillance after CRC resection combines both radiographic/CEA monitoring and colonoscopy surveillance. History/physical and CEA: every 3–6 months for 2 years, then every 6 months for a total of 5 years. CT chest/abdomen/pelvis: every 6–12 months for the first 2–3 years. Colonoscopy: 1 year after surgery; if normal, repeat in 3 years; then every 5 years if normal. Option B (only colonoscopy) misses the imaging and CEA surveillance component. Option C lacks CEA and has no colonoscopy schedule. Option D incorrectly uses PET/CT — this is NOT recommended for routine CRC surveillance.
[/expand]PN is a 40-year-old woman who received FOLFOX for stage IV CRC. After 2 cycles she began to complain of erythema, blistering, fissures, and pain in her palms that interfere with her household routine. Which of the following is correct regarding management of her syndrome?
- Continue dose, use urea 20% cream BID plus clobetasol 0.05% cream daily
- Continue dose, use urea 20% cream BID plus clobetasol 0.05% cream daily plus pain control with NSAIDs or GABA agonists or opioids
- Hold till recovery to grade 0 or grade 1, use urea 20% cream BID plus clobetasol 0.05% cream daily plus pain control with NSAIDs or GABA agonists or opioids
- Continue dose, use urea 20% cream BID plus clobetasol 0.05% cream daily plus pain control with NSAIDs or GABA agonists or opioids
Answer: C. Hold till recovery to grade 0 or grade 1, use urea 20% cream BID plus clobetasol 0.05% cream daily plus pain control with NSAIDs or GABA agonists or opioids
Explanation: The patient is describing hand-foot syndrome (HFS) / palmar-plantar erythrodysesthesia — a common toxicity of fluoropyrimidines (5-FU in FOLFOX). The described symptoms (blistering, fissures, pain interfering with activities) are consistent with Grade 2 or 3 HFS. Standard management requires holding the causative chemotherapy until symptoms improve to Grade 0–1, followed by dose reduction upon re-challenge. Symptomatic support includes urea cream (emollient), clobetasol (topical steroid), and analgesics (NSAIDs for inflammation, GABA agonists such as gabapentin for neuropathic pain, or opioids for severe pain). Options A, B, and D all incorrectly advise continuing the chemotherapy at the same dose, which would worsen the toxicity.
[/expand]Which of the following is correct regarding patient education about oxaliplatin?
A. Avoid cold drinks and ice for 3–5 days after infusion to prevent laryngospasm and dysphagia
B. The most common side effect is nephrotoxicity
C. It is associated with delayed diarrhea
D. It is associated with acneiform rash
Explanation: Oxaliplatin causes an acute, cold-induced neurotoxicity. This can manifest as throat tightness, difficulty swallowing, laryngospasm, and paresthesias upon cold exposure. Patients must be counseled to avoid cold drinks, ice, and cold surfaces for several days after infusion. The most common and dose-limiting toxicity of oxaliplatin is cumulative sensory neuropathy (numbness, tingling in hands/feet) — NOT nephrotoxicity (option B is incorrect). Delayed diarrhea is the hallmark toxicity of irinotecan — not oxaliplatin (option C is incorrect). Acneiform (papulopustular) rash is a classic toxicity of EGFR inhibitors (cetuximab, panitumumab) — not oxaliplatin (option D is incorrect).
[/expand]A 55-year-old man with a history of stage III colon cancer status post resection and adjuvant FOLFOX 3 years ago presents for routine follow-up. He has no complaints. CEA is 1.5 ng/mL (normal < 2.5). CT scan shows a new 1.5 cm pulmonary nodule in the right lower lobe with the remainder of the scan stable. What is the next best step?
A. Refer for thoracoscopic wedge resection of the nodule
B. Obtain a PET/CT scan
C. Repeat CT chest in 3 months
D. Start FOLFIRI chemotherapy
Explanation: This patient has a new solitary pulmonary nodule in the context of prior stage III colon cancer — raising concern for metastatic recurrence. His CEA is normal, but this does not rule out recurrence since CEA is not always elevated in metastatic disease. A PET/CT scan is the next best step because it assesses the metabolic activity of the nodule (distinguishing benign from malignant), evaluates for other sites of disease not apparent on CT, and guides further management (biopsy, resection, or systemic therapy). Thoracoscopic wedge resection (option A) is premature without confirming malignancy or ruling out other disease. Repeat CT in 3 months (option C) may be reasonable for indeterminate nodules in low-risk patients — but this patient has a high-risk history, making PET/CT more appropriate. Starting FOLFIRI (option D) is not appropriate without confirming recurrence or systemic disease.
[/expand]A 60-year-old woman with stage IV KRAS mutant colon cancer with liver metastases is being treated with FOLFIRI and bevacizumab. She calls to report 8 episodes of high-volume watery diarrhea yesterday, starting about 12 hours after her last chemotherapy infusion 2 days ago. She also reports mild abdominal cramping. She is afebrile and is still able to drink fluids. What is the best management?
A. Instruct her to take loperamide 4 mg now, then 2 mg after every loose stool, up to 16 mg/day
B. Instruct her to go to the emergency department for IV fluids and octreotide
C. Instruct her to start ciprofloxacin 500 mg twice daily for 7 days
D. Reassure her that this is expected and will resolve in 1–2 days
Explanation: The timing (12 hours after infusion) and description are classic for irinotecan-induced delayed-onset diarrhea (note: although described as "early onset" in the original, the timing of 12 hours after infusion with high-volume watery diarrhea is consistent with irinotecan-related diarrhea managed with loperamide). The standard loperamide regimen is a 4 mg loading dose followed by 2 mg every 2–4 hours or after every loose stool (not to exceed 16 mg in 24 hours). Emergency IV fluids and octreotide (option B) are for severe or complicated diarrhea not controlled by loperamide — she is still able to drink fluids. Antibiotics (option C) would be for suspected infectious diarrhea — less likely given the classic post-chemotherapy timing. Reassurance alone (option D) is incorrect — this requires active management.
[/expand]A 45-year-old man with metastatic rectal cancer receiving FOLFIRI and bevacizumab presents to the ED with a 1-day history of severe abdominal pain and distention. He has not had a bowel movement or passed flatus for 2 days. His last chemotherapy was 1 week ago. He is afebrile with HR 110 bpm. The abdomen is diffusely tender and tympanitic without peritonitis. An abdominal X-ray shows significantly dilated loops of large bowel. What is the most likely diagnosis?
A. Ogilvie syndrome (acute colonic pseudo-obstruction)
B. Bevacizumab-induced bowel perforation
C. Irinotecan-induced colitis
D. Diverticulitis
Explanation: Ogilvie syndrome is a pseudo-obstruction where the colon becomes massively dilated without a mechanical cause. It is a known complication in hospitalized or debilitated patients and can be triggered by medications, metabolic imbalances, and various systemic conditions. The presentation — severe distention, pain, no bowel movements or flatus, diffuse tympanitis without peritonitis, and dilated large bowel loops on X-ray without free air — is classic for Ogilvie syndrome. Bevacizumab-induced perforation (option B) would typically present more acutely with signs of peritonitis and free air on X-ray — neither is described here. Irinotecan-induced colitis (option C) causes diarrhea — not obstipation and massive dilation. Diverticulitis (option D) would likely present with fever, localized pain (often left lower quadrant), and not with the same degree of diffuse colonic dilation.
[/expand]SECTION 4: PANCREATIC CANCER
CONCEPTUAL SUMMARY
Overview: Pancreatic ductal adenocarcinoma carries a very poor prognosis. Treatment decisions depend on resectability, performance status, comorbidities, and molecular profile.
Adjuvant Therapy (Post-Whipple/Resection):
- mFOLFIRINOX is the preferred adjuvant regimen for patients with good performance status (ECOG 0–1) based on the PRODIGE 24/CCTG PA trial.
- Gemcitabine + capecitabine is an alternative regimen based on the ESPAC-4 trial — preferred for patients with baseline neuropathy (avoids oxaliplatin from FOLFOX component of FOLFIRINOX) or reduced performance status.
- Gemcitabine alone is an option if the patient cannot tolerate combination regimens.
- Gemcitabine + nab-paclitaxel has insufficient data for adjuvant treatment at this time.
- Gemcitabine + cisplatin is NOT a currently recommended adjuvant regimen. Observation has shown inferior results to chemotherapy in the adjuvant setting.
Metastatic Pancreatic Cancer
- First-Line: mFOLFIRINOX or gemcitabine + nab-paclitaxel are preferred for patients with good performance status (ECOG 0–1).
- Gemcitabine alone is appropriate for ECOG PS 2–3.
- Gemcitabine + erlotinib is not a preferred NCCN regimen despite a Category 1 recommendation.
- For patients with BRCA1/2 or PALB2 mutations: platinum-based therapy is preferred — either mFOLFIRINOX or gemcitabine + cisplatin. Following 4–6 months of platinum-based therapy with a response, olaparib maintenance is an option for BRCA1/2-mutated metastatic pancreatic cancer.
Metastatic Pancreatic Cancer — Second-Line and Beyond: After gemcitabine-based therapy: 5-FU/leucovorin + liposomal irinotecan is an accepted second-line option. After FOLFIRINOX: gemcitabine + nab-paclitaxel or gemcitabine + cisplatin (for BRCA-mutated disease) are appropriate. For MSI-H tumors: pembrolizumab is appropriate in subsequent-line therapy — it is NOT indicated in the first-line setting for patients with good performance status even if MSI-H.
Key Points: mFOLFIRINOX is preferred for BRCA-mutated metastatic pancreatic cancer because it contains oxaliplatin (a platinum agent). If the patient progresses after FOLFIRINOX on maintenance olaparib, gemcitabine + cisplatin is appropriate for BRCA-mutated disease in the subsequent-line given their platinum-sensitive status. Patients who relapse early after ASCT (< 12 months) in other cancers are treated with clinical trials — this concept applies similarly to early relapse in pancreatic cancer.
PRACTICE QUESTIONS — PANCREATIC CANCER
JM is a 65-year-old male who underwent a Whipple procedure for resectable pancreatic cancer 10 weeks ago. He did not receive neoadjuvant therapy. ECOG PS is 0 and his goal is to return to golfing 2–3 times per week. Which of the following is the most appropriate adjuvant treatment for JM?
A. Observation
B. Gemcitabine
C. Gemcitabine + nab-paclitaxel
D. mFOLFIRINOX
Explanation: mFOLFIRINOX as a preferred regimen for adjuvant treatment of resected pancreatic cancer for patients with good performance status. JM has ECOG PS 0 and no contraindications, making him an ideal candidate. Observation (option A) has shown inferior results to chemotherapy in the adjuvant setting. Gemcitabine alone (option B) would be an option only if JM was unable to tolerate mFOLFIRINOX or gemcitabine + capecitabine. Gemcitabine + nab-paclitaxel (option C) is not currently recommended for adjuvant treatment — insufficient data exist at this time.
[/expand]ZT is a 78-year-old female who underwent a Whipple procedure for resectable pancreatic cancer 11 weeks ago. She did not receive neoadjuvant therapy. ECOG PS is 1. Her medical history is pertinent for diabetic neuropathy in her feet requiring a walker. Which of the following is the most appropriate adjuvant treatment for ZT?
A. Observation
B. Gemcitabine + capecitabine
C. Gemcitabine + nab-paclitaxel
D. mFOLFIRINOX
Explanation: Based on results from the ESPAC-4 trial, both NCCN and ASCO guidelines support gemcitabine + capecitabine as a regimen for adjuvant treatment of resected pancreatic cancer. Due to ZT's baseline diabetic neuropathy, avoidance of agents that could worsen her neuropathy is prudent — mFOLFIRINOX contains oxaliplatin, which causes cumulative sensory neuropathy and would significantly worsen her existing condition. Observation (option A) has shown inferior results to adjuvant chemotherapy. Gemcitabine + nab-paclitaxel (option C) is not currently recommended for adjuvant treatment — insufficient data. mFOLFIRINOX (option D) is preferred for good performance status patients without neuropathy — ZT's baseline neuropathy makes this inappropriate despite it being a preferred option in general.
[/expand]TS is a 60-year-old male with metastatic pancreatic cancer confirmed with adenocarcinoma in the liver consistent with a pancreatic primary. ECOG PS is 0. Both sisters have had breast cancer and his mother had ovarian cancer. Genetic workup reveals a deleterious germline BRCA2 mutation. Which of the following is the most appropriate initial treatment for TS's metastatic pancreatic cancer?
A. Gemcitabine
B. Gemcitabine + erlotinib
C. Gemcitabine + nab-paclitaxel
D. mFOLFIRINOX
Explanation: TS has ECOG PS 0, minimal symptoms, no pertinent comorbidities, good family support, and a goal to treat — making him a good candidate for aggressive chemotherapy with mFOLFIRINOX. Additionally, his BRCA2 mutation requires platinum-based chemotherapy — mFOLFIRINOX contains oxaliplatin (a platinum agent), making it doubly appropriate. Patients with BRCA1/2 mutations should receive platinum-containing regimens. Gemcitabine alone (option A) is only appropriate for ECOG PS 2–3 — TS is PS 0. Gemcitabine + erlotinib (option B) is not considered a preferred regimen. Gemcitabine + nab-paclitaxel (option C) is not the most appropriate for TS because he is BRCA2-mutated and should receive platinum-based chemotherapy — gemcitabine + nab-paclitaxel does not contain a platinum agent.
[/expand]TS received 6 cycles of mFOLFIRINOX complicated by grade 2 neuropathy (oxaliplatin dropped). He eventually switched to olaparib maintenance therapy. His CT now shows new lung lesions and enlarged liver lesions. His neuropathy has resolved to grade 1. ECOG is now 1. What would be most appropriate subsequent therapy for TS?
A. Gemcitabine
B. 5-FU + radiation
C. Gemcitabine + cisplatin
D. Best supportive care
Explanation: Due to TS's BRCA2 mutation and good performance status (ECOG 1), he should be offered gemcitabine + cisplatin in the subsequent-line setting. BRCA-mutated tumors are generally platinum-sensitive, and despite prior exposure to oxaliplatin, cisplatin represents a different platinum agent that may still confer benefit. Gemcitabine alone (option A) would be considered if TS had a poor performance status or was otherwise ineligible for cisplatin. 5-FU + radiation (option B) is incorrect given his extra-pancreatic sites of disease — radiation could be considered if he were experiencing pain or obstruction from his tumor. Best supportive care (option D) would not be considered at this time given his good performance status and ability to receive further treatment.
[/expand]TS is a 60-year-old male with metastatic pancreatic cancer, ECOG PS 0, and high microsatellite instability (MSI-H) on molecular workup. He also has a KRAS mutation. His bilirubin normalized to 1.6 mg/dL after biliary stent placement. Which of the following is the most appropriate initial treatment for TS's metastatic pancreatic cancer?
A. Gemcitabine
B. Gemcitabine + erlotinib
C. Gemcitabine + nab-paclitaxel
D. Pembrolizumab
Explanation: TS has ECOG PS 0, no pertinent comorbidities, minimal symptoms, and a goal to treat — making him a good candidate for aggressive chemotherapy. Gemcitabine + nab-paclitaxel or mFOLFIRINOX are both appropriate first-line options for good performance status patients. Gemcitabine alone (option A) is only appropriate for ECOG PS 2–3. Gemcitabine + erlotinib (option B) is not considered a preferred regimen by NCCN Guidelines. Pembrolizumab (option D) is NOT appropriate in the first-line setting for a patient with good performance status — although TS's tumor is MSI-H, pembrolizumab is appropriate only in subsequent-line therapy for MSI-H metastatic pancreatic cancer. The presence of KRAS mutation also does not change the first-line chemotherapy recommendation.
[/expand]TS received 6 cycles of gemcitabine + nab-paclitaxel complicated by grade 2 neuropathy. His CT now shows new lung lesions and enlarged liver lesions. All labs are within normal limits. ECOG is now 1. His tumor is MSI-H. What would be most appropriate subsequent therapy for TS?
A. Capecitabine
B. 5-FU + radiation
C. Pembrolizumab
D. Best supportive care
Explanation: Pembrolizumab is appropriate for MSI-H patients in the subsequent-line setting after prior chemotherapy. 5-FU/leucovorin + liposomal irinotecan is also an acceptable second-line chemotherapy option for metastatic pancreatic cancer previously treated with gemcitabine-based chemotherapy, but pembrolizumab is specifically indicated for MSI-H disease. Capecitabine alone (option A) would be considered if TS had a poor performance status. 5-FU + radiation (option B) is incorrect given his extra-pancreatic sites of disease — radiation could only be considered for pain or local obstruction. Best supportive care (option D) would not be considered at this time given TS's good performance status and ability to receive further treatment.
[/expand]SECTION 5: GASTROINTESTINAL STROMAL TUMOR (GIST)
CONCEPTUAL SUMMARY
Definition and Pathophysiology: GIST is the most common mesenchymal tumor of the GI tract, arising from interstitial cells of Cajal (the pacemaker cells of the gut). The stomach is the most common site (~60%), followed by the small intestine (~30%), colon/rectum, and esophagus. Median age at diagnosis is in the 60s.
Molecular Biology:
- KIT mutations (~75–80%) cause constitutive activation of KIT (CD117) and are the most common driver mutation.
- PDGFRA mutations (~5–10%) — the most common PDGFRA mutation is D842V (imatinib-resistant; treat with avapritinib).
- Rarer subtypes include SDH-deficient, NTRK, BRAF, and NF1-associated GIST. Immunohistochemistry: CD117 (KIT+) and DOG1+ confirm diagnosis. Mutation testing is ESSENTIAL before initiating therapy.
Localized Disease: Surgery is curative if resectable. Adjuvant imatinib 400 mg PO daily is recommended for ≥ 3 years (and increasingly up to 6 years based on recent data) in high-risk disease based on tumor size, mitotic rate, site, and mutation status. Neoadjuvant imatinib is used to shrink borderline resectable tumors before surgery.
Metastatic/Unresectable GIST — Standard Treatment Sequence:
- First-line: imatinib 400 mg daily (800 mg daily for KIT exon 9 mutation).
- Second-line: sunitinib (50 mg daily, 4 weeks on/2 weeks off, or continuous 37.5 mg) after imatinib progression or intolerance.
- Third-line: regorafenib (160 mg daily, 3 weeks on/1 week off).
- Fourth-line: ripretinib (150 mg daily, continuous) after ≥ 3 prior TKIs.
- Special: avapritinib (300 mg daily) is indicated for PDGFRA exon 18 mutations (especially D842V) — these are resistant to imatinib.
- Maintaining kinase inhibition at all times is critical — stopping therapy leads to rapid tumor growth.
TKI Toxicities:
- Imatinib: edema, rash, GI upset, hepatotoxicity, cytopenias — NO pleural effusion (pleural effusion = dasatinib).
- Sunitinib: hypertension, hand-foot syndrome, hypothyroidism, cardiotoxicity, mucositis.
- Regorafenib: hepatotoxicity, hand-foot skin reaction (HFSR), hypertension, diarrhea.
- Ripretinib: alopecia, myalgia, fatigue, skin toxicity.
- Avapritinib: cognitive effects, intracranial bleeding (monitor mental status and neurologic status carefully).
Autologous HSCT: NO role in GIST (as in CML).
PRACTICE QUESTIONS — GIST
A patient with metastatic GIST has progressed on imatinib and sunitinib. His oncologist is considering third-line therapy. Molecular testing shows a KIT exon 11 mutation with no PDGFRA D842V mutation. Which of the following is the most appropriate third-line therapy for this patient?
A. Avapritinib
B. Imatinib 800 mg daily
C. Regorafenib
D. Ripretinib
Answer: C. Regorafenib
Explanation: The standard treatment sequence for metastatic GIST is imatinib → sunitinib → regorafenib → ripretinib. This patient has progressed on both imatinib (first-line) and sunitinib (second-line), making regorafenib the appropriate third-line choice. Regorafenib is dosed at 160 mg daily on a 3-weeks-on/1-week-off schedule. Avapritinib (option A) is specifically indicated for PDGFRA exon 18 mutations, especially D842V — this patient has a KIT exon 11 mutation, not a PDGFRA D842V mutation, so avapritinib is not the appropriate choice. Imatinib 800 mg daily (option B) is the standard dose for KIT exon 9 mutations in the first-line setting — it is not appropriate in the third-line setting after prior imatinib failure. Ripretinib (option D) is the fourth-line option after ≥ 3 prior TKIs — this patient has only failed 2 TKIs, making regorafenib the appropriate next step.
[/expand]A patient with newly diagnosed GIST is found to have a PDGFRA D842V mutation on molecular testing. The tumor is unresectable and the patient requires systemic therapy. Which of the following is the most appropriate first-line therapy?
A. Imatinib 400 mg daily
B. Imatinib 800 mg daily
C. Sunitinib
D. Avapritinib
Explanation: PDGFRA D842V mutations are resistant to imatinib — both at standard dose (400 mg) and higher dose (800 mg). They are also resistant to most other TKIs in the GIST treatment sequence. Avapritinib is specifically designed and FDA-approved for PDGFRA exon 18 mutations, especially D842V, and is the treatment of choice for this mutation regardless of line of therapy. Imatinib 400 mg daily (option A) and 800 mg daily (option B) are both inappropriate because the PDGFRA D842V mutation confers resistance to imatinib. Sunitinib (option C) is second-line therapy after imatinib failure in KIT-mutated GIST — it is not appropriate for PDGFRA D842V-mutated disease as first-line therapy. Mutation testing is essential before therapy, as this case illustrates.
[/expand]A patient with high-risk resected GIST (based on tumor size, mitotic rate, and site) has completed 3 years of adjuvant imatinib. He is disease-free and asks whether he should continue therapy. Which of the following statements is most accurate regarding adjuvant imatinib duration?
- Three years of adjuvant imatinib is the maximum recommended duration — no further benefit beyond this
- Imatinib can be stopped after 3 years since the patient is disease-free
- Stopping imatinib after 3 years is associated with risk of recurrence — extended therapy up to 6 years may be considered based on improved recurrence-free survival data
- D. Lifelong imatinib is mandatory for all patients with high-risk resected GIST
Answer: C. Stopping imatinib after 3 years is associated with risk of recurrence — extended therapy up to 6 years may be considered based on improved recurrence-free survival data
Explanation: For high-risk resected GIST, 3 years of adjuvant imatinib was the initial standard based on improved recurrence-free survival compared to 1 year of therapy. More recent data support extending adjuvant imatinib to 6 years, showing further improvement in recurrence-free survival — the risk of recurrence upon stopping imatinib is real and well-documented. NCCN updates now include the option of extended adjuvant therapy for up to 6 years in high-risk patients. Stopping after 3 years without consideration of extended therapy (option B) does not account for this updated evidence. Lifelong imatinib is typically reserved for patients with metastatic disease, where TKI must be maintained continuously — it is not a blanket requirement for all adjuvant patients (option D is overstated).
[/expand]A patient with GIST who has been receiving imatinib for metastatic disease develops disease progression. His oncologist switches him to sunitinib. After several months, the patient develops fatigue, significant hair loss, and alopecia, along with muscle aches. Which TKI in the GIST treatment sequence is most likely responsible for these specific toxicities?
A. Imatinib
B. Sunitinib
C. Regorafenib
D. Ripretinib
Explanation: While this patient is currently on sunitinib, the question asks which TKI in the GIST treatment sequence is most associated with alopecia (hair loss) and myalgia (muscle aches) as characteristic toxicities. Ripretinib's key toxicities include alopecia, myalgia, fatigue, and skin toxicity — these are its distinguishing side effects. Imatinib (option A) is associated with edema, rash, GI upset, hepatotoxicity, and cytopenias — not alopecia or significant myalgia. Sunitinib (option B) is associated with hypertension, hand-foot syndrome, hypothyroidism, cardiotoxicity, and mucositis — not alopecia as a defining feature. Regorafenib (option C) is associated with hepatotoxicity, hand-foot skin reaction, hypertension, and diarrhea — not alopecia or myalgia as cardinal features.
[/expand]8. A 66-year-old patient with metastatic colorectal cancer is receiving FOLFOX with bevacizumab. After the third cycle, the patient was admitted to the hospital for a pulmonary embolus. After being discharged home with a prescription of Dalteparin, the patient returns to the clinic for additional chemotherapy. Should bevacizumab therapy be continued? Which is the best option?
- A. This patient developed a venous thromboembolic disease (VTE) which is not found with bevacizumab. Bevacizumab causes arterial embolic events so bevacizumab can be restarted. (5%)
- B. Bevacizumab may have been the VTE cause; however the patient is receiving dalteparin so the risk of recurrence is minimized. Restart bevacizumab. (6%)
- C. Bevacizumab should not be restarted since patients on bevacizumab have a higher risk of recurrent VTEs and a higher risk of bleeding with concomitant anticoagulation and bevacizumab than without bevacizumab. (7%)
- D. Since this patient developed a VTE while on chemotherapy and bevacizumab, the patient’s colorectal cancer has progressed. Discontinue bevacizumab. (3%)
- In a study of over 1400 metastatic colorectal cancer patients. VTE was present more in the bevacizumab arm: 13.5% vs. 9.6%.
- Over 100 patients were treated with anticoagulants following the initial VTE, and the overall incidence of subsequent VTE was higher in the bevacizumab arm: 31.5% vs. 25.6%.
- The overall incidence of bleeding was higher in the bevacizumab arm: 27.4% vs. 20.9%.
- Based on this information, bevacizumab should be withheld due to an increased risk of VTE and bleeding from bevacizumab.
47. A patient is started on panitumumab for their metastatic colorectal cancer. Two weeks after starting therapy, she presents to the oncologist with a rash on her face and upper trunk. There are signs of folliculitis with pustules present. What strategy could have been implemented at the start of therapy to minimize or prevent this acneiform rash?
- A. At the first sign of the rash, she needs to begin to apply topical benzoyl peroxide until rash disappears. (7%)
- B. Before panitumumab is started, she should be applying skin moisturizers, sunblock to exposed areas if going outdoors, topical steroids, and doxycycline (75%)
- C. Before the panitumumab is initiated, she begins picrolimus cream to face and trunk with moisturizers (6%)
- D. Before panitumumab is started, tazarotene 0.05% cream to face and trunk with sunscreen (10%)
- A study evaluating the use of pre-emptive therapies vs. starting at rash onset showed a 50% reduction in a significant rash with the pre-emptive approach using hydrocortisone 1% with moisturizer, sunscreen, and either doxycycline or minocycline.
- Prevent the skin from drying out and protect it from the sun. Do not use acne medications since this disease is NOT acne.
- Use antibiotics prophylactically or at the onset of pustule formation.
- Topical tazarotene or pimecrolimus is not recommended.
60. HT is a 54-year-old male with metastatic colorectal cancer who is receiving cetuximab. Which of the following side effects should he be counseled on?
- A. Otc prolongation (18%)
- B. Hypomagnesemia (54%)
- C. Arterial thromboembolism (15%)
- D. Bleeding (13%)
- Hypomagnesemia is a relatively common side effect associated with epidermal growth factor receptor (EGFR) inhibitors such as cetuximab and panitumumab.
- Although the mechanism responsible for this electrolyte imbalance is not well understood, increased EGFR expression in the ascending loop of Henle may lead to renal tubular damage and interfere with magnesium reabsorption.
- Electrolytes should be monitored routinely and for eight weeks after the completion of anti-EGFR therapy as magnesium levels typically return to normal.
- QTc prolongation, arterial thromboembolism, and bleeding are not commonly associated with cetuximab.
- Although not as common as other side effects, hypomagnesemia has been associated with cetuximab and panitumumab. The patient’s electrolytes should be frequently monitored during the duration of EGFR inhibitor treatment and for approximately eight weeks afterward.
- Hypomagnesemia secondary to anti-EGFR therapy can lead to cardiovascular, neuromuscular, and behavioral symptoms and can also be associated with hypocalcemia. This type of hypocalcemia is due to hypomagnesemia-induced parathyroid hormone (PTH) resistance and can only be corrected by replacing magnesium.
84. HR is a 68-year-old man with metastatic colorectal cancer and wild-type KRAS genotype, who is scheduled to receive cetuximab plus irinotecan therapy. He recently moved from Tennessee and has noted his allergies have improved since moving. After receiving his antiemetic premedication of dexamethasone and ondansetron, he began his 90-minute infusion of irinotecan. Thirty minutes into the infusion, he received another premedication of diphenhydramine for his cetuximab. After the irinotecan finished, the cetuximab loading dose began to infuse over a planned 2 hours. Within 5 minutes of the infusion, he developed a hypersensitivity reaction and then anaphylaxis. What predictive risk factors did HR possess for a cetuximab allergic reaction?
- A. Geographical location, history of allergies (44%)
- B. Rate of infusion of cetuximab, administration of irinotecan first (21%)
- C. History of allergies, rate of cetuximab infusion (25%)
- D. Insufficient premedications, geographical location (10%)
- There is a higher prevalence of patients with anaphylactic reactions to cetuximab in Tennessee, North Carolina, and Arkansas (Southeast area).
- These patients have pre-existing IgE antibodies to galactose-alpha-1,3 galactose, which is present on the Fab portion of the heavy chain of cetuximab.
- Also, patients with an atopic history or previous hypersensitivity reactions have a higher risk for these anaphylactic reactions.
- This patient received all of the recommended premedications, and the length of cetuximab infusion was administered over the appropriate length of time.