Cycle length: 8 weeks (treatment for 6 weeks followed by 2 weeks rest).*
Duration of therapy: 24 weeks (3 total cycles). |
| Drug | Dose and route | Administration | Given on days |
| Oxaliplatin | 85 mg/m2 IV | Dilute in 500 mL D5W¶ and administer over two hours prior to leucovorin and fluorouracil. Shorter oxaliplatin administration schedules (eg, 1 mg/m2 per minute) appear to be safe.[3] | Days 1, 15, and 29 |
| LeucovorinΔ | 500 mg/m2 IV | Dilute in 250 mL D5W¶ and administer over two hours (immediately following the completion of oxaliplatin, on the treatment days when oxaliplatin is administered). | Days 1, 8, 15, 22, 29, and 36 |
| Fluorouracil (FU) | 500 mg/m2 IV bolus | Slow IV push over five minutes (administer one hour after the start of the leucovorin infusion). | Days 1, 8, 15, 22, 29, and 36 |
| Pretreatment considerations: |
| Emesis risk | - FU/leucovorin (days 8, 22, and 36): LOW.
- Oxaliplatin plus FU/leucovorin (days 1, 15, 29): MODERATE.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Premedication is not routinely indicated for oxaliplatin, leucovorin, or FU.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Vesicant/irritant properties | - Oxaliplatin and FU are classified as irritants, but oxaliplatin can cause significant tissue damage; avoid extravasation. Many centers routinely infuse oxaliplatin through a central venous line because of local pain with infusion into a peripheral vein.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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| Infection prophylaxis | - Primary prophylaxis with granulocyte-colony stimulating factors is not recommended. Neutropenia with fever or infection incidence with this regimen is 4.8%.[1,2,4]
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
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| Dose adjustment for baseline liver or renal dysfunction | - Lower starting doses of FU and leucovorin may be needed for patients with liver impairment. A lower starting dose of oxaliplatin may be needed for severe renal impairment.
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents; and chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency, conventional cytotoxic agents.
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| Cardiopulmonary issues | - QT prolongation and ventricular arrhythmias have been reported after oxaliplatin. ECG monitoring is recommended if therapy is initiated in patients with heart failure, bradyarrhythmias, coadministration of drugs known to prolong the QT interval, and electrolyte abnormalities. Avoid oxaliplatin in patients with congenital long QT syndrome. Correct hypokalemia and hypomagnesemia prior to initiating oxaliplatin. Oxaliplatin has rarely been associated with pulmonary toxicity.
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| Maneuvers to prevent neurotoxicity | - Pharmacologic methods to prevent/delay the onset of oxaliplatin-related neuropathy are controversial due to the absence of large clinical trials proving benefit. Counsel patients to avoid exposure to cold during, and for approximately 48 hours after each infusion of oxaliplatin.
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
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| Monitoring parameters: |
- CBC with differential and platelet count prior to each treatment.
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- Assess electrolytes (especially potassium and magnesium) and liver and renal function prior to each treatment.
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- Assess changes in neurologic function prior to each treatment.
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- Monitor for diarrhea and palmar-plantar erythrodysesthesias.
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| Suggested dose modifications for toxicity |
| Myelotoxicity | - Delay treatment cycle by one week for ANC <1500/microL, or platelets <75,000/microL on the day of treatment.[5] For febrile neutropenia, grade 4 neutropenia, or grade 3 or 4 thrombocytopenia occurring during treatment, reduce subsequent oxaliplatin dose from 85 mg/m2 to 75 mg/m2 and reduce FU dose by 20%.[5]
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| Diarrhea | - The dose-limiting toxicity of this regimen is diarrhea. Affected patients should be closely monitored for dehydration, fever, and neutropenia, and use of adequate doses of antidiarrheal agents (eg, loperamide). Do not restart treatment until diarrhea is ≤grade 1.[6] If diarrhea severity exceeded grade 2, reduce subsequent oxaliplatin dose from 85 mg/m2 to 75 mg/m2 and reduce FU dose by 20%.[5]
- NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
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| Mucositis | - Hold FU for grade 3 or 4 mucositis, and resume at a 20% lower dose after resolution to ≤grade 1.[6]
- Refer to UpToDate topics on oral toxicity associated with chemotherapy.
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| Cardiotoxicity | - Cardiotoxicity observed with FU includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, ECG changes, and cardiomyopathy.
- Refer to UpToDate topics on fluoropyrimidine-associated cardiotoxicity.
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| Pulmonary toxicity | - Withhold oxaliplatin for unexplained pulmonary symptoms until interstitial lung disease or pulmonary fibrosis is excluded.
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
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| Neurologic toxicity | - For persistent grade 2 neurosensory toxicity in the adjuvant setting, it is recommended to reduce the oxaliplatin dose from 85 mg/m2 to 75 mg/m2. Discontinue oxaliplatin for persistent grade 3 neurosensory toxicity.[5,7]
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
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| Palmar-plantar erythrodysesthesia | - Hold FU for ≥grade 2 palmar plantar erythrodysesthesia, and resume with a 20% dose reduction after resolution to ≤grade 1.[6]
- Refer to UpToDate topics on cutaneous side effects of conventional chemotherapy agents.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
