GYNECOLOGICAL ONCOLOGY — COMPLETE STUDY GUIDE OVARIAN CANCER, CERVICAL CANCER, AND ENDOMETRIAL CANCER
SECTION 1: EPITHELIAL OVARIAN CANCER
CONCEPTUAL SUMMARY
Definition and Overview: Ovarian cancer includes fallopian tube and primary peritoneal cancers, which are distinct entities but managed identically. Approximately 85–90% of cases are sporadic, while 10–15% are hereditary. Germline BRCA1 mutations carry a 39–58% absolute risk; BRCA2 mutations carry a 13–29% risk. BRCA1 mutations are associated with earlier onset compared to BRCA2 mutations. BRCA1/2 mutations are actually FAVORABLE prognostic factors in ovarian cancer — they predict better response to platinum therapy. NCCN recommends genetic testing for ALL women diagnosed with ovarian cancer regardless of family history.
Screening and Prevention: There is NO effective screening for the general population — CA-125 and transvaginal ultrasound lack sufficient sensitivity and specificity. High-risk women (BRCA-mutated) should consider risk-reducing salpingo-oophorectomy (RRSO) between ages 35–40. Oral contraceptives used for over 5 years can reduce ovarian cancer risk by approximately 50%.
Primary Treatment by Stage: Early stage (I–II): Surgery for staging followed by 3–6 cycles of adjuvant platinum-based chemotherapy for high-risk patients. Stage IA/IB grade 1 (low-grade serous or grade 1 of other histology): Observation only — survival > 90% with surgery alone. Stage IB high-grade serous: 6 cycles of carboplatin/paclitaxel (NOT 3 cycles — based on GOG-157 subgroup analysis showing favorable RFS with 6 over 3 cycles for high-grade serous histology). Advanced stage (III–IV): Optimal cytoreduction (residual tumor < 1 cm) followed by 6 cycles of carboplatin/paclitaxel. For patients unlikely to achieve optimal debulking: neoadjuvant chemotherapy (NACT) followed by interval debulking surgery is preferred. Intraperitoneal (IP) chemotherapy is recommended for stage III optimally debulked (< 1 cm) patients based on GOG-172 showing a 16-month OS benefit: IV paclitaxel day 1 + IP cisplatin day 2 + IP paclitaxel day 8. IP therapy should NOT be used as neoadjuvant treatment. Bevacizumab-based combinations are NOT recommended for stage I disease — only for stage II–IV.
PARP Inhibitor Maintenance — Frontline: Olaparib 300 mg BID: approved for primary maintenance following CR or PR to platinum-based chemotherapy in patients with germline OR somatic deleterious BRCA1/2 mutations (SOLO-1). Does NOT require bevacizumab in frontline. Niraparib 300 mg once daily: the ONLY PARP inhibitor approved for primary maintenance independent of BRCA status (PRIMA trial) — appropriate for patients regardless of BRCA mutation when bevacizumab was NOT part of frontline therapy. Olaparib + bevacizumab: Category 1 recommendation for patients who received bevacizumab as part of frontline chemotherapy AND are HRD-positive (BRCA-mutated or HRD+) — PAOLA-1 trial showed OS benefit in HRD-positive patients. For BRCA-wt and HRD-negative patients who received bevacizumab frontline: olaparib + bevacizumab may still be considered based on PAOLA-1 data showing benefit in the overall population. Bevacizumab maintenance alone: reserved for patients who received bevacizumab-containing primary therapy (GOG-218 or ICON-7) — not appropriate as standalone maintenance if bevacizumab was not part of frontline. Rucaparib: NOT recommended for primary maintenance — used for recurrent platinum-sensitive maintenance or treatment after ≥ 2 prior lines.
Recurrent Ovarian Cancer: Platinum-sensitive recurrence (> 6 months since last platinum): continue platinum-based combination therapy. Preferred regimens include carboplatin + gemcitabine, carboplatin + pegylated liposomal doxorubicin (PLD) ± bevacizumab, carboplatin + paclitaxel (if no neuropathy concerns). If patient has neuropathy — avoid paclitaxel; use carboplatin + gemcitabine or carboplatin + PLD instead. Cisplatin causes MORE neuropathy than carboplatin — prefer carboplatin in patients with baseline neuropathy. Platinum-resistant recurrence (< 6 months since last platinum): non-platinum agents preferred. PLD monotherapy (Category 2A preferred). Mirvetuximab soravtansine-gynx: approved for platinum-resistant ovarian cancer in folate receptor alpha (FRα)-positive tumors. Niraparib + bevacizumab: based on AVANOVA2 trial — reserved for platinum-sensitive recurrence as a chemo-sparing option. Pembrolizumab: only appropriate if MSI-H or dMMR with NO satisfactory alternative — NOT for platinum-sensitive relapse (which has satisfactory alternatives), NOT as maintenance after platinum in recurrence (that role belongs to olaparib, rucaparib, or niraparib). Pembrolizumab is NOT the only PD-1 inhibitor approved for MSI-H solid tumors; nivolumab also has this indication but pembrolizumab is specifically mentioned in guidelines.
Low Malignant Potential (Borderline) Tumors: Observation only after optimal surgical debulking — adjuvant chemotherapy, PARP inhibitors, and bevacizumab are NOT indicated for borderline tumors.
Platinum Hypersensitivity Reaction Management: Platinum reactions typically occur after 6–8 exposures. Management of severe HSR: STOP the infusion, start oxygen, administer H1 and H2 blockers + corticosteroid. Steroids alone do not provide immediate benefit — they prevent rebound/delayed reactions. Epinephrine is reserved for life-threatening anaphylaxis only.
PRACTICE QUESTIONS — OVARIAN CANCER
JJ is a 57-year-old female staged with IB, high-grade serous ovarian cancer who underwent adequate surgical cytoreduction and staging. Which of the following is the most appropriate management for JJ at this time?
A. Carboplatin/paclitaxel for 3 cycles
B. Observation
C. Carboplatin/paclitaxel for 6 cycles
D. Carboplatin/paclitaxel/bevacizumab for 6 cycles
Explanation: Six cycles of platinum-based combination chemotherapy are recommended as adjuvant therapy for patients with early-stage, high-grade serous ovarian cancer. Based on a subgroup analysis of GOG-157, 6 cycles showed favorable recurrence-free survival over 3 cycles specifically for high-grade serous histology — making option A incorrect. Observation (option B) is only appropriate for stage IA/IB low-grade serous or grade 1 of other histology where survival exceeds 90% with surgery alone. Bevacizumab-based combination therapy (option D) is not currently recommended for stage I disease — bevacizumab may be utilized for stage II–IV disease.
[/expand]JJ is a 57-year-old female staged with IA grade 1 ovarian cancer who underwent adequate surgical cytoreduction and staging. Which of the following is the most appropriate management for JJ at this time?
A. Neoadjuvant chemotherapy
B. Observation
C. Adjuvant chemotherapy
D. Hormone therapy
Explanation: Observation is recommended in patients with stage IA or IB disease who have been appropriately staged by a gynecologic oncologist — survival exceeds 90% in this group with surgery alone. Neoadjuvant chemotherapy (option A) is not appropriate because JJ has already undergone surgical staging and debulking, and neoadjuvant therapy is not indicated in early-stage disease. Adjuvant chemotherapy (option C) could be considered if the patient did not undergo adequate surgical staging — but JJ did undergo appropriate staging, making observation alone appropriate. Hormone therapy (option D) is not indicated for early-stage ovarian cancer.
[/expand]SM has clinical stage IVB high-grade serous ovarian cancer (pleural effusions and liver lesions) and is deemed unlikely to achieve optimal cytoreduction upon imaging and surgical consultation. Which of the following is the most appropriate initial therapy for SM?
A. Staging TAH/BSO followed by adjuvant chemotherapy
B. IP/IV carboplatin + paclitaxel followed by interval debulking surgery
C. Dose-dense paclitaxel IV + carboplatin IV followed by interval debulking surgery
D. Carboplatin + gemcitabine + bevacizumab
Explanation: SM has stage IVB ovarian cancer and was deemed unlikely to achieve optimal cytoreduction. Neoadjuvant chemotherapy followed by interval debulking surgery is most appropriate. Staging surgery followed by adjuvant chemotherapy (option A) is not appropriate — patients who are unfit for surgery or unlikely to be optimally debulked should receive neoadjuvant chemotherapy prior to surgical cytoreduction. Intraperitoneal (IP) therapy (option B) should NOT be used as neoadjuvant treatment — IP therapies may be used following interval debulking surgery in appropriately selected patients. Carboplatin + gemcitabine + bevacizumab (option D) is a preferred regimen for platinum-sensitive recurrence — not frontline therapy.
[/expand]SM has clinical stage IVB high-grade serous ovarian cancer and is deemed unlikely to achieve optimal cytoreduction. Which of the following is the most appropriate initial therapy for SM?
A. Staging TAH/BSO followed by carboplatin + paclitaxel
B. IP/IV carboplatin + paclitaxel followed by interval debulking surgery
C. Carboplatin + paclitaxel followed by interval debulking surgery
D. Carboplatin + gemcitabine + bevacizumab
Explanation: SM has stage IVB ovarian cancer and was deemed unlikely to achieve optimal cytoreduction. Neoadjuvant chemotherapy (carboplatin + paclitaxel) followed by interval debulking surgery is the most appropriate approach. Staging surgery followed by adjuvant chemotherapy (option A) is not appropriate for patients unlikely to be optimally debulked — neoadjuvant chemotherapy is preferred. IP/IV therapy (option B) should NOT be used as neoadjuvant treatment — it may be considered after interval debulking surgery. Carboplatin + gemcitabine + bevacizumab (option D) is a preferred regimen for platinum-sensitive recurrence — not frontline therapy.
[/expand]SM completed 3 cycles of neoadjuvant chemotherapy, underwent interval debulking surgery with optimal cytoreduction, and completed 3 more cycles of adjuvant carboplatin + paclitaxel achieving a complete response. Germline and tumor genetic testing showed no BRCA1/2 pathogenic alterations. SM would like to pursue maintenance therapy. Which of the following would you recommend?
A. Bevacizumab 15 mg/kg every 3 weeks
B. Niraparib 300 mg once daily
C. Olaparib 300 mg twice daily
D. No maintenance therapy because she does not have a germline or somatic BRCA mutation
Explanation: Niraparib is the only PARP inhibitor approved for primary maintenance therapy following a CR or PR to platinum-based chemotherapy independent of BRCA status — based on the PRIMA trial. This makes it the appropriate choice for SM who is BRCA-wild type. Bevacizumab maintenance (option A) should be reserved for patients who received bevacizumab-containing primary therapy per GOG-218 or ICON-7 — SM's frontline regimen did not include bevacizumab. Olaparib (option C) for frontline maintenance requires that the patient have a germline or somatic deleterious BRCA1/2 mutation — SM has no such mutation. Option D is incorrect because niraparib primary maintenance is approved regardless of BRCA status.
[/expand]SM completed 3 cycles of neoadjuvant chemotherapy, interval debulking surgery, and 3 more cycles of adjuvant carboplatin + paclitaxel + bevacizumab achieving a partial response. Germline testing showed BRCA-wild type. Tumor NGS showed HRD-negative. SM would like to pursue maintenance therapy. Which of the following would you recommend?
A. Niraparib 300 mg once daily
B. Rucaparib 600 mg twice daily
C. Olaparib 300 mg twice daily
D. Olaparib 300 mg twice daily plus bevacizumab 15 mg/kg every 3 weeks
Explanation: Based on the PRIMA data, niraparib showed a progression-free survival benefit in all patients with a CR or PR to platinum-based therapy in the frontline setting regardless of BRCA or HRD status — including HRD-negative patients. This is a Category 2A recommendation in NCCN guidelines. Since SM received bevacizumab as part of frontline therapy, continuing bevacizumab maintenance is also an option — but if the patient is interested in a PARP inhibitor and is HRD-negative/BRCA-wt, niraparib is the appropriate choice. Rucaparib (option B) is not recommended for primary maintenance — it may be used for recurrent platinum-sensitive maintenance or treatment after ≥ 2 prior lines. Olaparib monotherapy (option C) for frontline maintenance requires a germline or somatic deleterious BRCA mutation — SM has neither. Olaparib + bevacizumab (option D) is recommended for patients who received bevacizumab frontline AND are HRD-positive (BRCA-mutated or HRD+) — SM is HRD-negative, making this combination less appropriate than niraparib monotherapy per NCCN guidelines.
[/expand]SM completed 3 cycles of neoadjuvant chemotherapy, interval debulking surgery, and 3 more cycles of adjuvant carboplatin + paclitaxel + bevacizumab achieving a partial response. Germline testing showed BRCA-wild type. Tumor NGS showed homologous recombination deficient (HRD) positive. SM would like to pursue maintenance therapy. Based on NCCN guidelines, which of the following would you recommend?
A. Niraparib 300 mg oral once daily
B. Rucaparib 600 mg oral twice daily
C. Olaparib 300 mg oral twice daily
D. Olaparib 300 mg oral twice daily plus bevacizumab 15 mg/kg every 3 weeks
Explanation: Based on the PAOLA-1 trial, olaparib + bevacizumab showed an overall survival benefit in HRD-positive patients with a CR or PR to platinum-based therapy in the frontline setting when bevacizumab was received as part of frontline chemotherapy. This is a Category 1 recommendation in NCCN guidelines for patients who received bevacizumab as part of upfront chemotherapy with at least a partial response and who are HRD-positive (BRCA-mutated or HRD+). Niraparib (option A) is not the preferred choice per NCCN guidelines because the patient received bevacizumab as part of her upfront chemotherapy — olaparib + bevacizumab is preferred. Rucaparib (option B) is not preferred for primary maintenance, especially when the patient received bevacizumab frontline. Olaparib monotherapy (option C) for frontline maintenance requires a germline or somatic deleterious BRCA mutation — SM does not have one; her HRD-positive status without BRCA mutation requires the combination with bevacizumab.
[/expand]SM completed 3 cycles of neoadjuvant chemotherapy, interval debulking surgery, and 3 more cycles of adjuvant carboplatin + paclitaxel achieving a partial response. Tumor genetic testing revealed a somatic deleterious mutation in BRCA1. SM would like to pursue maintenance therapy. Which of the following would you recommend?
A. Bevacizumab 15 mg/kg every 3 weeks
B. Olaparib 300 mg twice daily
C. Niraparib 300 mg once daily
D. No maintenance therapy because she does not have a germline BRCA mutation
Explanation: Olaparib is approved for primary maintenance therapy following a CR or PR to platinum-based chemotherapy for patients with either germline OR somatic deleterious BRCA1/2 mutations — based on the SOLO-1 trial. SM has a somatic deleterious BRCA1 mutation, making her eligible for olaparib maintenance. Bevacizumab maintenance (option A) should be reserved for patients who received bevacizumab-containing primary therapy — SM's frontline regimen did not include bevacizumab. Niraparib (option C) is approved for primary maintenance independent of BRCA status — however, since SM has a BRCA mutation, olaparib is the preferred and most appropriate option. Option D is incorrect — olaparib primary maintenance is approved for use in patients with both germline AND somatic BRCA mutations.
[/expand]SM presents to clinic after 3 months of niraparib maintenance therapy. Her adjuvant chemotherapy was complicated by grade 2 peripheral neuropathy. She presents with worsening abdominal distension and CT scan confirms new lymphadenopathy — consistent with disease recurrence 3 months after completing initial platinum-based adjuvant chemotherapy. Which of the following regimens is most appropriate for SM?
A. Carboplatin + gemcitabine
B. Pegylated liposomal doxorubicin (PLD)
C. Niraparib + bevacizumab
D. Pembrolizumab
Explanation: SM experienced progression 3 months following completion of initial platinum-based adjuvant chemotherapy — this classifies her disease as platinum-resistant recurrence (progression < 6 months from last platinum). For platinum-resistant recurrence, non-platinum single agents are preferred. PLD monotherapy is a Category 2A preferred therapy for platinum-resistant recurrence. Carboplatin + gemcitabine (option A) is a platinum-based regimen — inappropriate for platinum-resistant disease. Niraparib + bevacizumab (option C) is based on the AVANOVA2 trial and should be reserved for platinum-sensitive recurrence as a chemotherapy-sparing option — not platinum-resistant recurrence. Pembrolizumab (option D) is only appropriate for advanced solid tumors with dMMR, MSI-H, or TMB-H — this tumor was not determined to be dMMR based on the information provided; additionally, platinum-resistant recurrence does not qualify as having "no satisfactory alternative" if other agents are available.
[/expand]SM presents to clinic 2 years after completing adjuvant chemotherapy which was complicated by grade 2 peripheral neuropathy. She has remained on niraparib maintenance but CT scan confirms new lymphadenopathy — consistent with disease recurrence. SM is concerned about worsening peripheral neuropathy. Which of the following regimens is most appropriate for SM?
A. IV carboplatin + gemcitabine
B. IV carboplatin + paclitaxel
C. IV liposomal doxorubicin + bevacizumab
D. IV cisplatin + gemcitabine
Explanation: SM experienced recurrence 2 years after completing platinum-based therapy — this classifies her disease as platinum-sensitive recurrence (> 6 months from last platinum). Platinum-based combination chemotherapy is recommended for platinum-sensitive disease. However, given her grade 2 peripheral neuropathy and explicit concern about worsening neuropathy, paclitaxel should be avoided. Carboplatin can be combined with gemcitabine or liposomal doxorubicin in lieu of paclitaxel to prevent further neuropathy exacerbation. Carboplatin + paclitaxel (option B) is inappropriate given her grade 2 neuropathy and explicit concern — re-exposing her to paclitaxel is not ideal. IV liposomal doxorubicin + bevacizumab (option C) without a platinum is inappropriate for a patient with platinum-sensitive disease in the first relapse — this could be considered in platinum-resistant disease. Cisplatin + gemcitabine (option D) is inappropriate because cisplatin would be expected to cause more neuropathy than carboplatin — the least neuropathic platinum option should be preferred.
[/expand]SM presents to clinic after 10 months of olaparib + bevacizumab maintenance therapy. Her adjuvant chemotherapy was complicated by grade 2 peripheral neuropathy. CT scan confirms new lymphadenopathy — consistent with disease recurrence. Which of the following regimens is most appropriate for SM?
A. Carboplatin + pegylated liposomal doxorubicin
B. Gemcitabine
C. Mirvetuximab soravtansine-gynx
D. Pembrolizumab
Explanation: SM experienced recurrence 10 months after completing initial platinum-based adjuvant chemotherapy — this classifies her disease as platinum-sensitive recurrence (> 6 months from last platinum). Platinum-based combination chemotherapy is recommended for platinum-sensitive disease. Given her grade 2 peripheral neuropathy, paclitaxel should be avoided — carboplatin + pegylated liposomal doxorubicin is a Category 2A preferred regimen for platinum-sensitive recurrent ovarian cancer that avoids further neuropathy. Gemcitabine alone (option B) is inappropriate for platinum-sensitive recurrence — the patient should continue to receive a platinum combination if able to tolerate. Mirvetuximab soravtansine-gynx (option C) is only currently approved in platinum-resistant ovarian cancer — SM has platinum-sensitive disease; additionally, folate receptor alpha (FRα) status is unknown. Pembrolizumab (option D) is only appropriate for dMMR, MSI-H, or TMB-H tumors with no satisfactory alternative — SM has platinum-sensitive disease with satisfactory platinum-based alternatives available.
[/expand]SM presents to clinic 15 months after completing adjuvant chemotherapy complicated by grade 2 peripheral neuropathy. She has remained on olaparib maintenance but CT scan confirms new lymphadenopathy — consistent with disease recurrence. SM is concerned about worsening peripheral neuropathy. Which of the following regimens is most appropriate for SM?
A. IV carboplatin + liposomal doxorubicin B. IV carboplatin + paclitaxel C. IV liposomal doxorubicin + bevacizumab D. IV cisplatin + gemcitabine
[expand] Answer: A. IV carboplatin + liposomal doxorubicinExplanation: SM experienced recurrence 15 months after completing platinum-based therapy — platinum-sensitive recurrence. Platinum-based combination chemotherapy is recommended for platinum-sensitive disease. Carboplatin would be preferred over cisplatin with regard to potential for exacerbating peripheral neuropathy. Carboplatin + liposomal doxorubicin avoids taxane re-exposure in a patient with grade 2 neuropathy and explicit concern. Carboplatin + paclitaxel (option B) is inappropriate given her grade 2 neuropathy and explicit concern about a taxane — re-exposure is not ideal. IV liposomal doxorubicin + bevacizumab without a platinum (option C) is inappropriate for platinum-sensitive disease in first relapse — this could be considered for platinum-resistant disease. Cisplatin + gemcitabine (option D) is inappropriate because cisplatin causes more neuropathy than carboplatin — carboplatin is the preferred platinum in patients with baseline neuropathy.
[/expand]SM completed 3 cycles of neoadjuvant chemotherapy, interval debulking surgery, and 3 more cycles of carboplatin + paclitaxel + bevacizumab achieving a partial response. Germline testing: BRCA-wild type. Tumor NGS: HRD-negative. SM would like to pursue maintenance therapy. Which of the following would you recommend?
A. Niraparib 300 mg once daily
B. Talazoparib 1 mg once daily
C. Olaparib 300 mg twice daily
D. Olaparib 300 mg twice daily plus bevacizumab 15 mg/kg every 3 weeks
Explanation: This patient received frontline bevacizumab-containing chemotherapy and achieved a partial response. She is BRCA-wild type and HRD-negative. The PAOLA-1 trial demonstrated that olaparib + bevacizumab as maintenance therapy significantly improved PFS compared to bevacizumab alone for patients who received frontline platinum-based chemotherapy with bevacizumab — with benefit observed in the overall population including HRD-negative patients, though the magnitude was greater in HRD-positive patients. Continuing bevacizumab as part of maintenance is standard of care following a bevacizumab-containing frontline regimen. PAOLA-1 builds on this by adding olaparib for additional benefit. Niraparib monotherapy (option A) does not include continuation of bevacizumab — since this patient received bevacizumab frontline, the standard of care is to continue it in maintenance, and PAOLA-1 evidence supports olaparib + bevacizumab. Talazoparib (option B) is not approved for ovarian cancer maintenance therapy. Olaparib monotherapy (option C) is for BRCA-mutated patients — SM is BRCA-wild type.
[/expand]SM has now received 5 lines of chemotherapy, most recently topotecan monotherapy, with confirmed progressive disease. She inquires about immunotherapy for treatment of ovarian cancer. Which of the following is true?
- Nivolumab is FDA-approved for microsatellite instability-high (MSI-H) solid tumors
- Pembrolizumab is only appropriate if MSI-H or dMMR when there is no satisfactory alternative
- Pembrolizumab may be given as maintenance therapy following a PR/CR to platinum-based therapy for recurrent disease
- Checkpoint blockade may be given in platinum-sensitive relapse
Explanation: Pembrolizumab should be reserved for treatment of relapsed ovarian cancer that is MSI-H or dMMR in which there are no satisfactory alternatives. Option A is incorrect — pembrolizumab (not nivolumab) is the FDA-approved PD-1 inhibitor for MSI-H solid tumors. Option C is incorrect — pembrolizumab is not appropriate for maintenance therapy in recurrent ovarian cancer; the recommended maintenance agents following platinum-based therapy for recurrent disease are olaparib, rucaparib, and niraparib. Option D is incorrect — patients with platinum-sensitive relapse have satisfactory platinum-based alternatives available, and therefore would not qualify as having "no satisfactory alternative" to receive pembrolizumab.
[/expand]During SM's initial adjuvant chemotherapy with paclitaxel and carboplatin following interval debulking surgery, she experienced a severe hypersensitivity reaction on cycle 6 of carboplatin, characterized by cough and shortness of breath. Which of the following is the proper management of a severe platinum hypersensitivity reaction?
A. Stop infusion, give corticosteroid, monitor for 30 minutes and resume at a slower rate
B. Stop infusion, start oxygen and observe
C. Administer IM epinephrine
D. Stop infusion, start oxygen, administer H1 and H2 blocker and corticosteroid
Explanation: Stopping the offending agent is always the first step in any hypersensitivity reaction, followed by oxygen support and appropriate pharmacologic intervention. Both H1 AND H2 antagonists are needed to stop the acute hypersensitivity reaction; corticosteroids prevent a delayed or rebound reaction. Steroids alone (option A) do not provide immediate benefit in managing an acute hypersensitivity reaction — they work slowly and primarily prevent rebound reactions; resuming the infusion after a severe reaction is also inappropriate without desensitization. Option B lacks pharmacologic intervention — observation alone is insufficient for a severe reaction. Option C (IM epinephrine) misses the critical first step of stopping the offending agent and providing oxygen — additionally, this reaction was not reported as life-threatening anaphylaxis and other interventions should be considered first before epinephrine.
[/expand]A 63-year-old woman underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, lymphadenectomy, and omental biopsies demonstrating bilateral ovarian tumors with lymph node involvement, omental caking, and ascites. Tumor was debulked to less than 1 cm of residual disease. Pathology demonstrates high-grade serous adenocarcinoma. She has recovered well from surgery with no significant comorbidities. What is the next best step in treatment?
- Observation
- Adjuvant hormonal therapy with an aromatase inhibitor for 5 years
- Intravenous carboplatin and paclitaxel every 3 weeks for six cycles
- Intravenous paclitaxel on day 1, intraperitoneal cisplatin on day 2, and intraperitoneal paclitaxel on day 8 of a 21-day cycle for six cycles
- Intravenous carboplatin and docetaxel every 3 weeks for six cycles
Explanation: In women with stage III optimally debulked (< 1 cm of residual disease) high-grade epithelial ovarian cancer who are otherwise fit, intraperitoneal chemotherapy is recommended based on the overall survival benefit of 16 months demonstrated in GOG-172 compared to standard intravenous platinum-based therapy. The IP/IV regimen involves IV paclitaxel on day 1, IP cisplatin on day 2, and IP paclitaxel on day 8 of a 21-day cycle for 6 cycles. Observation (option A) is inappropriate for high-grade serous ovarian cancer — adjuvant chemotherapy is required. Hormonal therapy (option B) is not the next step for high-grade serous ovarian cancer. Standard IV carboplatin + paclitaxel (option C) is an appropriate alternative but is not the most appropriate choice when the patient is a candidate for IP therapy given its proven OS advantage. Carboplatin + docetaxel (option E) is an alternative regimen but does not have the same level of evidence as the IV/IP regimen for this scenario.
[/expand]A 42-year-old woman underwent surgical staging for a pelvic mass demonstrating a 5 cm ovarian mass with capsular rupture and multiple peritoneal implants without evidence of invasion. She was optimally debulked with less than 1 cm of residual disease. Pathology demonstrates an epithelial serous ovarian tumor of low malignant potential (LMP). Which of the following is the best next step?
- Adjuvant intravenous carboplatin and paclitaxel for three to six cycles
- Intravenous paclitaxel on day 1, intraperitoneal cisplatin on day 2, and intraperitoneal paclitaxel on day 8 of a 21-day cycle for six cycles
- Observation
- Intravenous carboplatin and paclitaxel with bevacizumab every 3 weeks for six cycles followed by 6 months of bevacizumab maintenance therapy
- Initiate olaparib at 400 mg daily
Explanation: This patient was diagnosed with an epithelial serous ovarian tumor of low malignant potential (LMP), also known as a borderline malignancy — these tumors are associated with a good prognosis and do NOT require adjuvant therapy. Unlike invasive epithelial ovarian cancers, borderline tumors have a very low risk of aggressive recurrence when non-invasive. Even with peritoneal implants and capsular rupture, the achievement of optimal debulking (< 1 cm residual disease) and the absence of invasive disease means adjuvant chemotherapy or targeted therapies are not indicated. Platinum-based chemotherapy (options A and B) is the standard of care for invasive ovarian cancer — not for borderline tumors. Bevacizumab (option D) is utilized for stage III–IV invasive ovarian cancer, not borderline malignancies. Olaparib (option E) is a PARP inhibitor for maintenance in patients with invasive BRCA-mutated or HRD-positive disease — not appropriate here.
[/expand]A 49-year-old woman was diagnosed at age 43 with high-grade serous adenocarcinoma of the ovary and has had multiple recurrences. She is currently undergoing treatment with her third line of chemotherapy. She denies a family history of breast or ovarian cancer. Which of the following is correct?
A. BRCA1/2 testing is not indicated as it will not affect the management of her disease
B. NCCN guidelines recommend genetic testing given her personal history of ovarian cancer
C. BRCA1/2 mutations are negative prognostic factors in ovarian cancer
D. Germline heterozygous BRCA2 mutations convey a higher risk for developing ovarian cancer at a younger age compared to BRCA1 mutations
Explanation: NCCN recommends genetic testing for ALL women diagnosed with ovarian cancer regardless of family history — mutational status may affect treatment options including olaparib (a PARP inhibitor approved for recurrent ovarian cancer with germline BRCA1/2 mutations). Option A is incorrect — BRCA testing absolutely affects management, including eligibility for PARP inhibitors. Option C is incorrect — BRCA1/2 mutations are actually FAVORABLE prognostic factors in ovarian cancer — associated with better prognosis and predictive of response to platinum therapy. Option D is incorrect — BRCA1 mutations (NOT BRCA2) convey a higher risk of earlier onset of ovarian cancer compared to BRCA2 mutations.
[/expand]SECTION 2: CERVICAL CANCER
CONCEPTUAL SUMMARY
Definition and Etiology: Cervical cancer is a malignancy of the uterine cervix arising from epithelial cells of the cervical transformation zone. It is almost exclusively caused by persistent infection with oncogenic HPV strains — HPV 16 and 18 are responsible for approximately 70% of all cervical cancer cases. Other high-risk HPV types include 31, 33, 45, 52, and 58. HPV 6 and 11 cause genital warts — NOT cervical cancer. In addition to cervical cancer, HPV is responsible for ~90% of anal cancers, ~71% of vulvar/vaginal/penile cancers, and ~72% of oropharyngeal cancers.
Most common histology: Squamous cell carcinoma (~70–80%). Other types include adenocarcinoma (~20%) and adenosquamous.
HPV Vaccination: The 9-valent HPV vaccine is now approved for males and females aged 9–45. CDC recommends the HPV vaccine series (3 shots) for males aged 9–21 and females aged 9–26. The preferred vaccination age is 11 or 12 years old. Males at high risk for HPV (homosexual, immunosuppressed) should be vaccinated up to age 26. All sexually active women is too broad — the recommendation is age-based.
Screening: For ages 30–65: cytology alone every 3 years OR co-testing with HPV DNA every 5 years.
Treatment by Stage: Early stage (IA–IB1): Surgery (radical hysterectomy with pelvic lymphadenectomy) or radiation. Fertility-sparing: conization or radical trachelectomy. Locally advanced (IIB–IVA): Concurrent chemoradiation — EBRT + brachytherapy + weekly cisplatin 40 mg/m² IV as radiosensitizer. Addition of cisplatin to pelvic radiation decreases risk of death from cervical cancer by 30–50%. Stage IVA: Primary chemoradiation (not surgery — stage IVA is not a surgical candidate). Stage IVB (distant metastatic): Systemic chemotherapy is the standard of care — goal is palliation and prolonging survival. First-line: cisplatin or carboplatin + paclitaxel + bevacizumab (GOG-240 trial showed improved OS with bevacizumab addition). For PD-L1 positive tumors (CPS ≥ 1): adding pembrolizumab to platinum doublet + bevacizumab is a Category 1 preferred recommendation. Second-line: tisotumab vedotin-tftv (antibody-drug conjugate requiring strict ocular prophylaxis — steroid/lubricating drops and ice packs).
Key Rules: Radiation with chemoradiation in locally advanced disease — concurrent cisplatin is mandatory. Bevacizumab in first-line metastatic/recurrent setting — improves OS (GOG-240). Pembrolizumab in first-line recurrent/metastatic: only when PD-L1 CPS ≥ 1 is confirmed; if PD-L1 status is unknown or failed testing, pembrolizumab should NOT be added. Surgery is NOT appropriate for stage IVA or IVB.
PRACTICE QUESTIONS — CERVICAL CANCER
DD is a 55-year-old female with stage IVA cervical cancer — squamous cell carcinoma with left parametrial invasion and rectal involvement on imaging. What management options are available for this patient?
A. Surgery
B. Radiation
C. Chemoradiation
D. Chemotherapy
Explanation: Given the local metastatic disease (stage IVA), the therapy of choice is primary chemoradiation. Treatment includes external beam whole pelvic radiotherapy (EBRT) plus chemosensitization with weekly cisplatin 40 mg/m² IV, followed by high-dose rate brachytherapy. Surgery (option A) is not appropriate — DD has stage IVA disease and is not a surgical candidate. Radiation alone (option B) and chemotherapy alone (option D) as single-modality therapies are not appropriate — multiple trials have demonstrated that the addition of concurrent cisplatin to pelvic radiation decreases the risk of death from cervical cancer by 30–50% compared to either modality alone.
[/expand]DD completed successful chemoradiation and has been under active surveillance. At her 2-year follow-up, CT chest shows diffuse pulmonary nodules consistent with metastatic cervical cancer. PD-L1 testing was attempted on a prior tissue sample but failed. Which of the following every-3-week treatment options would be most appropriate for DD according to NCCN Guidelines?
A. Cisplatin 50 mg/m² + paclitaxel 175 mg/m² + bevacizumab 15 mg/kg
B. Cisplatin 50 mg/m²
C. Topotecan 1.5 mg/m² days 1–5 D.
Pembrolizumab 200 mg
Explanation: The most appropriate treatment for DD is combination chemotherapy with cisplatin, paclitaxel, and bevacizumab. The GOG-240 trial demonstrated improved overall survival with the addition of bevacizumab to combination chemotherapy in recurrent/metastatic cervical cancer. Cisplatin alone (option B) and topotecan alone (option C) are not the most appropriate options — multiple trials have demonstrated that patients receiving 2-drug combinations for relapsed metastatic cervical cancer had higher response rates and improved PFS compared to single-agent therapy. Pembrolizumab (option D) is not the most appropriate treatment because DD's PD-L1 status is unknown (testing failed) — pembrolizumab requires confirmed PD-L1 positivity (CPS ≥ 1) or confirmed MSI-H/dMMR status before use in the first-line setting.
[/expand]It is recommended that a human papillomavirus (HPV) vaccine series be administered to which of the following patient populations?
A. Only males 9 to 21 years old
B. Only females 9 to 26 years old
C. All sexually active women
D. Males 9 to 21 years old and females 9 to 26 years old
E. It is not recommended as routine vaccination for any patients
Explanation: The CDC recommends that an HPV vaccine series (consisting of three shots) be administered to males aged 9 to 21 and females aged 9 to 26 years. The preferred age for vaccination is 11 or 12 years old. Males who are at high risk for HPV infection (homosexual, immunosuppressed) should receive the vaccination series up to age 26 if not previously vaccinated. Note: The 9-valent HPV vaccine is now additionally approved for males and females aged 27–45, but the standard CDC recommendation referenced in this question covers the ages described in option D.
[/expand]A 32-year-old woman presents with stage IVB squamous cell carcinoma of the cervix. What is the preferred first-line treatment?
A. Chemotherapy with cisplatin, paclitaxel, and bevacizumab
B. Surgery with radical hysterectomy (uterus, cervix, parametrium, and upper vagina)
C. Pelvic radiation with chemosensitization
D. Surgery with simple hysterectomy (uterus and cervix only)
Explanation: Stage IVB is classified as distant metastatic disease — the goal of therapy shifts from cure to palliation and prolonging survival. Platinum-based combination chemotherapy is the standard of care for advanced (IVB) or recurrent disease. Cisplatin, paclitaxel, and bevacizumab is a preferred first-line regimen and a Category 1 recommendation based on GOG-240 showing improved overall survival compared to chemotherapy alone. Surgery (options B and D) is reserved for early-stage disease (stage I–IIA) — it has no role in primary treatment of metastatic stage IVB disease. Pelvic radiation with chemosensitization (option C) is the standard of care for locally advanced disease (bulky stage IIB, III, and IVA) — in stage IVB, radiation is typically individualized and used for palliation of specific symptoms, not as primary frontline systemic treatment.
[/expand]The majority of cervical cancer worldwide is believed to be secondary to infection with which strains of the human papillomavirus (HPV)?
A. HPV 6 and 11
B. HPV 16 and 18
C. HPV 34 and 36
D. HPV 56 and 62
Explanation: HPV 16 and 18 are associated with approximately 70% of all cervical cancer cases — they are the primary oncogenic strains responsible for cervical carcinogenesis. HPV 6 and 11 (option A) are responsible for the majority of genital and anal warts — they are low-risk types that do NOT cause cancer. In addition to cervical cancer, HPV infection is responsible for approximately 90% of anal cancers, 71% of vulvar/vaginal/penile cancers, and 72% of oropharyngeal cancers. HPV 34, 36, 56, and 62 (options C and D) are not the primary oncogenic strains associated with the majority of cervical cancer cases.
[/expand]SECTION 3: ENDOMETRIAL CANCER
CONCEPTUAL SUMMARY
Definition and Pathogenesis: Endometrial cancer is the most common gynecologic malignancy in the United States. The primary etiology is excess estrogen exposure. Risk factors include obesity (excess adipose tissue converts androgens to estrogen), nulliparity, late menopause, exogenous estrogen therapy without progestin, tamoxifen use, and diabetes.
Molecular Subtypes (TCGA): POLE-mutated: excellent prognosis. MSI-H/dMMR: intermediate prognosis; highly responsive to immunotherapy. Copy-number low (endometrioid): favorable prognosis. p53-mutant (serous-like): poor prognosis — requires aggressive multimodality care.
Lynch Syndrome (HNPCC): Found in approximately 5% of women with endometrial cancer. Characterized by loss of DNA mismatch repair (MMR) proteins — MLH1, MSH2, MSH6, PMS2. UNIVERSAL testing: immunohistochemistry of tumor tissue for MMR protein loss is the accepted initial screening method. Referral for genetic counseling is recommended if protein stains are ABSENT (loss of proteins indicates dMMR/possible Lynch syndrome). Mutation carriers have a 40–60% lifetime risk of Lynch-related cancers. All patients with newly diagnosed endometrial cancer should have age-appropriate colonoscopy screening recommended.
Staging and Treatment by Stage: Stage IA (grade 1/2, < 50% myometrial invasion, no LVSI, < 2 cm): Observation is appropriate following surgery. Stage IB (> 50% myometrial invasion): Vaginal brachytherapy (observation or brachytherapy for grade 1/2 without high-risk features; brachytherapy preferred for higher intermediate risk including age > 60, LVSI, or deep invasion). Stage IB grade 1 with LVSI and advanced age: adjuvant radiation therapy (vaginal brachytherapy) is recommended. Stage III–IV: Carboplatin + paclitaxel is the standard frontline chemotherapy. Recent Category 1 recommendations include adding pembrolizumab or dostarlimab to the carboplatin/paclitaxel doublet regardless of MMR status for advanced disease.
Recurrent Endometrial Cancer: Local recurrence (vagina, previously unirradiated): pelvic EBRT + brachytherapy or surgical exploration with resection. Symptomatic disseminated metastases: systemic chemotherapy is most appropriate. Asymptomatic disseminated metastases with ER/PR-positive, low-grade histology: hormonal therapy — aromatase inhibitors, megestrol, or tamoxifen. Hormonal therapy is well-tolerated and most effective for low-grade metastatic disease without large symptom burden or rapidly growing disease. For tumors not MSI-H/dMMR after prior systemic therapy: lenvatinib + pembrolizumab is the preferred regimen.
Key Rules: Adjuvant chemotherapy is reserved for advanced-stage (III–IV) or high-grade (grade 3) disease — NOT for stage IB grade 1/2. Biologic agents (bevacizumab) have no routine role in adjuvant endometrial cancer. Radiation therapy (vaginal brachytherapy or EBRT) is the primary adjuvant tool for early-stage disease with intermediate/high-risk features. Hormonal therapy is only appropriate for asymptomatic patients with low-grade, ER/PR-positive disease. BRCA1/2 testing is NOT routinely indicated for endometrial cancer — MMR/Lynch testing is the appropriate genetic screening.
PRACTICE QUESTIONS — ENDOMETRIAL CANCER
SK is a 64-year-old morbidly obese woman who presents with post-menopausal vaginal bleeding. Endometrial biopsy reveals FIGO grade 1 endometrioid adenocarcinoma. She underwent total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic and para-aortic lymphadenectomy and biopsies. Final pathology: grade 1 endometrioid adenocarcinoma, 1.1 cm invasion into a 1.7 cm myometrium (> 50% invasion), negative cervix, adnexa, and pelvic washings. No lymphovascular space invasion and negative lymph nodes — staged as IB grade 1.
What further therapy, if any, should SK receive?
A. Paclitaxel 175 mg/m² + carboplatin (AUC 6) every 21 days for 6–8 cycles
B. Observation or vaginal brachytherapy
C. Doxorubicin 45 mg/m² + cisplatin 50 mg/m² every 21 days for 6 cycles
D. Tamoxifen 20 mg daily
Explanation: SK has early-stage IB grade 1 endometrial cancer (tumor invades more than one-half of the myometrium). Given her low-risk, early-stage disease with no adverse risk factors (no LVSI, negative nodes, grade 1), observation or vaginal brachytherapy is recommended. Systemic chemotherapy (options A and C) is only appropriate for advanced endometrial cancer (stage III–IV) or high-grade (grade 3) disease — not for stage IB grade 1. Anti-hormonal therapy such as tamoxifen (option D) is only considered for advanced or recurrent endometrial cancer with hormone receptor positivity — not for early-stage adjuvant management.
[/expand]SK has been under active surveillance for 2 years and is found to have local recurrence confined to the vagina (no prior radiation or brachytherapy to the site of recurrence). Which of the following is the most appropriate treatment for SK at this time?
A. Surgical resection and intraoperative radiation therapy
B. Chemotherapy
C. Pelvic EBRT and brachytherapy
D. Hormone therapy
Explanation: SK has local recurrence confined to the vagina. Since she has not had prior radiation or brachytherapy to the site of recurrence, she is eligible for pelvic EBRT plus brachytherapy or surgical exploration with resection. Isolated vaginal recurrences treated with radiation therapy alone have good local control with 5-year survival rates of 50–70%. Surgical resection with intraoperative radiation therapy (option A) is a Category 3 recommendation — less preferred than EBRT + brachytherapy. Chemotherapy (option B) and hormone therapy (option D) are considered for patients with local recurrence who have previously undergone external beam radiation therapy — SK has not received prior radiation, making locoregional radiation the appropriate first choice.
[/expand]SK received EBRT and brachytherapy followed by active surveillance. At follow-up she reports shortness of breath. Laboratory tests show an elevated CA-125 and imaging reveals lung, pelvic, and para-aortic metastases. Which of the following is the most appropriate treatment for SK at this time?
A. Chemotherapy
B. Hormone therapy
C. Surgical resection
D. Radiation therapy
Explanation: SK has symptomatic disseminated metastases — chemotherapy is the most appropriate treatment. For symptomatic or rapidly progressive disseminated metastases, systemic chemotherapy (carboplatin + paclitaxel) is indicated. Hormone therapy (option B) would only be considered for a patient with ASYMPTOMATIC disseminated metastases or poor performance status with low-grade, ER/PR-positive disease — SK is symptomatic. Surgical resection (option C) and radiation therapy (option D) are not appropriate for disseminated metastatic disease — NCCN guidelines recommend pharmacologic intervention as most appropriate for disseminated disease.
[/expand]A 71-year-old otherwise healthy female presents with postmenopausal bleeding. Surgical staging revealed a 2.3 cm grade 1 endometrioid adenocarcinoma invading 1.2 cm into a 2 cm myometrium (> 50% invasion) with positive lymphovascular invasion. Disease was confined to the uterus without cervical involvement. What is the next step in treatment?
A. Observation
B. Adjuvant radiation therapy
C. Adjuvant platinum-based chemotherapy followed by radiation therapy
D. Adjuvant concurrent chemoradiation
Explanation: This patient has stage IB endometrioid endometrial cancer (> 50% myometrial invasion) with several high-intermediate risk factors: age 71, deep myometrial invasion, and positive LVSI. For stage IB grade 1 or 2 endometrial cancer, the preferred adjuvant treatment is vaginal brachytherapy (a form of radiation therapy) to reduce the risk of local pelvic relapse. Observation (option A) is appropriate for low-risk stage IA patients (grade 1/2, no LVSI, small tumor) — this patient has multiple risk factors making observation insufficient. Adjuvant systemic chemotherapy followed by radiation (option C) is typically reserved for advanced-stage (III–IV) disease or high-grade (grade 3) stage IB/II tumors — not for stage IB grade 1. Concurrent chemoradiation (option D) is the standard for locally advanced cervical cancer — it is not a standard adjuvant recommendation for stage I endometrioid endometrial cancer.
[/expand]A 56-year-old woman recently diagnosed with endometrial cancer presents to discuss recommended genetic screening. She was adopted and does not know any of her family history. She has not had a colonoscopy. Which of the following is true?
- No further testing is recommended
- Recommend age-appropriate colon cancer screening and immunohistochemical staining of tumor tissue for MLH1, MSH2, MSH6, and PMS2. Refer for genetic counseling if protein stains are retained
- Recommend age-appropriate colon cancer screening and immunohistochemical staining of tumor tissue for MLH1, MSH2, MSH6, and PMS2. Refer for genetic counseling if protein stains are absent
- Recommend germline BRCA1/2 testing
Explanation: HNPCC (Lynch syndrome) is found in approximately 5% of women with endometrial cancer. It is characterized by loss of DNA mismatch repair proteins — MLH1, MSH2, MSH6, and PMS2. Immunohistochemistry of tumor tissue looking for LOSS of these MMR proteins is the accepted initial screening method to identify women who should be referred for germline genetic testing. Referral for genetic counseling is indicated when protein stains are ABSENT (loss = abnormal = possible Lynch syndrome) — NOT when they are retained. Option B is incorrect because referral should occur when stains are absent (abnormal), not retained (normal). Age-appropriate colonoscopy screening is also recommended given her Lynch syndrome risk and unknown family history. BRCA1/2 testing (option D) is not routinely indicated for endometrial cancer — MMR/Lynch testing is the appropriate genetic screening. No further testing (option A) is incorrect — universal MMR testing is recommended for all newly diagnosed endometrial cancers.
[/expand]A 68-year-old female presents with biopsy-proven recurrent grade 1 endometrioid endometrial adenocarcinoma metastatic to the lung and pelvis. Tumor tissue stains positive for estrogen receptor. She is asymptomatic from her current disease. She has residual peripheral neuropathy from previous adjuvant carboplatin and paclitaxel chemotherapy completed 1 year ago. What is the most appropriate next step in management?
A. Hormonal therapy with an aromatase inhibitor
B. Doublet chemotherapy with a platinum and taxane
C. Surgical resection of dominant lung nodule
D. Doublet chemotherapy with a platinum and anthracycline
Explanation: Hormonal therapy (aromatase inhibitors, megestrol, or tamoxifen) is a well-tolerated treatment in women with low-grade metastatic endometrial cancer, especially with ER positivity. Hormonal therapy is most appropriate in women without large symptom burden or rapidly growing disease — it is most effective in controlling and/or slowing disease growth. This patient is ASYMPTOMATIC with low-grade, ER-positive metastatic disease, making hormonal therapy the ideal choice. Doublet chemotherapy (options B and D) would be appropriate for symptomatic patients or those with rapidly progressive disease — this patient is asymptomatic with low-grade disease. Surgical resection of the dominant lung nodule (option C) is not the next step — she has both lung and pelvic metastases indicating disseminated disease, making curative-intent surgery inappropriate.
[/expand]A 58-year-old woman was diagnosed with a 1 cm grade 1 endometrioid endometrial cancer after undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy for presumed benign indications. Disease invaded 0.2 cm into a 2 cm myometrium without lymphovascular invasion. What is the next best step in treatment?
A. Observation
B. Completion staging with pelvic and aortic lymphadenectomy
C. Adjuvant chemotherapy with carboplatin and paclitaxel
D. Adjuvant radiation therapy
Explanation: Observation is appropriate in this case. The patient has stage IA (< 50% myometrial invasion: 0.2 cm into a 2 cm myometrium = 10% invasion), grade 1 endometrioid endometrial cancer, no LVSI, and a tumor < 2 cm — all consistent with very low-risk early-stage disease. Survival is excellent with surgery alone for this profile. Further lymph node assessment (option B) is not needed given the very low risk of nodal involvement in this early-stage, grade 1 tumor. Adjuvant chemotherapy (option C) is reserved for advanced-stage (III–IV) or high-grade disease — not for low-risk stage IA grade 1 tumors. Adjuvant radiation therapy (option D) is not the next step for this very low-risk, early-stage disease.
[/expand]32. A 55-year-old woman with ovarian cancer is scheduled to receive her seventh cycle of carboplatin and paclitaxel. Her premedications before this regimen included palonosetron, diphenhydramine, ranitidine, and dexamethasone. Her paclitaxel was infused over three hours without incident; however, she developed acute shortness of breath and back pain during the infusion of carboplatin. What is the cause of her hypersensitivity reaction?
- A. Delayed onset paclitaxel reaction (26%)
- B. Acute carboplatin reaction (58%)
- C. Allergic reaction to palonosetron (2%)
- D. Drug interaction between the sequence strategy of paclitaxel and carboplatin (15%)
- Carboplatin is well known to produce a hypersensitivity reaction after six cycles of carboplatin. Patients who are receiving carboplatin should be monitored closely whenever they receive long courses of therapy.
- Paclitaxel almost exclusively produces hypersensitivity reactions during the first or second infusion. In addition, the reaction usually occurs during the infusion rather than hours later.
- There is no sequencing drug interaction between carboplatin and paclitaxel. This is unlike cisplatin and paclitaxel, which requires paclitaxel to be given first to minimize neutropenia risk.
- A You may administer either agent first (43%)
- B You should administer the paclitaxel first followed by cisplatin (65%)
- C You should administer the cisplatin first followed by paclitaxel (20%)
- D Avoid this combination since cisplatin and paclitaxel are inactive in ovarian cancer (2%)
[expand] Answer (B)
- Cisplatin should be administered after paclitaxel. The paclitaxel clearance values were 21% lower when paclitaxel followed cisplatin
- Also, when cisplatin preceded paclitaxel, the absolute neutrophil nadirs were lower, and grade 4 neutropenia was more common than when the paclitaxel was administered first.
[/expand]
139. GE is a 64-year-old female who is receiving her sixth cisplatin cycle for metastatic ovarian cancer. After reviewing her labs, it appears that GE is experiencing some nephrotoxicity from cisplatin. Which electrolyte abnormalities would be indicative of cisplatin-induced nephrotoxicity?
- A Hyperkalemia and hyperphosphatemia (27%)
- B Hyperkalemia and hypermagnesemia (4%)
- C Hypokalemia and hypophosphatemia (6%)
- D Hypokalemia and hypomagnesemia (48%)
- The glomerular filtration rate (GFR) decreases with repeated cisplatin cycles. Upon cisplatin cessation, renal function may or may not improve.
- Hypomagnesemia is a common finding from cisplatin administration and is due to a renal defect in magnesium reabsorption.
- Secondary wasting of calcium and potassium may accompany this situation.
- Another potential mechanism of cisplatin nephrotoxicity proposes a distal renal tubular acidosis leading to tubular wasting of hydrogen, magnesium, potassium, and calcium ions.