| Component | Drug | Typical Dose & Route | Schedule (q2 weeks) | Notes for Pharmacists |
|---|---|---|---|---|
| FOL | Leucovorin (LV) | 400 mg/m² IV over 2 hr (or 200 mg/m² depending on protocol) | Day 1 | Enhances binding of 5-FU to thymidylate synthase → ↑ cytotoxicity |
| F | Fluorouracil (5-FU) | Bolus: 400 mg/m² IV push Infusion: 2400–3000 mg/m² continuous IV over 46 hr |
Bolus: Day 1 Infusion: Day 1–3 |
Bolus linked to myelosuppression; infusion linked to hand-foot syndrome, mucositis |
| OX | Oxaliplatin | 85 mg/m² IV over 2 hr in D5W | Day 1 (given first) | Dose-limiting neuropathy; avoid cold exposure post-infusion |
Common Variants
- mFOLFOX6 – Most widely used modification; lower bolus 5-FU dose or omit to reduce toxicity.
- FOLFOX4 – Older version; more cumbersome, less used.
- CAPOX/XELOX – Oral capecitabine replaces 5-FU/leucovorin.
Indications
- Adjuvant: Stage III colon cancer (6 months standard; 3 months for low-risk per IDEA study)
- Metastatic colorectal cancer: 1st-line or later
- Other GI malignancies (gastric, pancreatic, biliary) off-label
Toxicity Profile & Monitoring
| Toxicity | Cause | Monitoring | Management Notes |
|---|---|---|---|
| Peripheral neuropathy (acute/cumulative) | Oxaliplatin | Neuro exam each cycle | Cold avoidance post-infusion; dose reduction if persistent |
| Myelosuppression | 5-FU bolus, oxaliplatin | CBC prior to each cycle | Hold/reduce dose for neutropenia, thrombocytopenia |
| GI toxicity (N/V, diarrhea, mucositis) | 5-FU, oxaliplatin | Symptom assessment | Antiemetics; loperamide PRN |
| Hand-foot syndrome | 5-FU infusion | Skin exam | Urea cream; dose adjust |
| Hypersensitivity reactions | Oxaliplatin | Observe during infusion | Slow rate, premedication if mild; discontinue if severe |
Administration Sequence
- Oxaliplatin IV over 2 hr (in D5W)
- Leucovorin IV over 2 hr (can be given concurrently with oxaliplatin via Y-site)
- 5-FU bolus IV push
- 5-FU continuous infusion via ambulatory pump for 46 hr
Pharmacist Clinical Pearls
- Oxaliplatin degrades in chloride solutions → only use D5W.
- Infusion pump patient education is crucial — proper handling, troubleshooting, disconnection.
- Monitor cumulative oxaliplatin dose (>850–1000 mg/m² → ↑ neuropathy risk).
- 5-FU toxicity risk ↑ in DPD deficiency — consider testing in severe/unexpected toxicity.
- Use cryotherapy (oral ice chips) during bolus 5-FU to reduce mucositis risk.
Synonyms
FOLFOX