| Cycle length: 21 days. |
| Drug | Dose and route | Administration | Given on days |
| Oxaliplatin | 130 mg/m2 IV | Dilute in 500 mL D5W* and administer over two hours. Shorter oxaliplatin administration schedules (eg, 1 mg/m2 per minute) appear to be safe.[2] | Day 1 |
| Capecitabine¶ | 750 mg/m2 orallyΔ | Twice daily (total daily dose 1500 mg/m2). Swallow whole with water within 30 minutes after a meal, with each dose as close to 12 hours apart as possible. Do not cut or crush tablets.◊ | Evening of day 1 to morning of day 15 |
| Pretreatment considerations: |
| Emesis risk | - Oxaliplatin: MODERATE.
- Oral capecitabine: LOW.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - There is no standard premedication regimen for oxaliplatin.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Vesicant/irritant properties | - Oxaliplatin is an irritant but can cause significant tissue damage; avoid extravasation.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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| Infection prophylaxis | - Primary prophylaxis with G-CSF not indicated.[1]
- 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 oxaliplatin and capecitabine may be needed for renal impairment.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency, conventional cytotoxic agents.
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| Maneuvers to prevent neurotoxicity | - Counsel patients to avoid exposure to cold during and for approximately 48 hours after each infusion. Prolongation of the oxaliplatin infusion time from two to six hours may mitigate acute neurotoxicity.
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
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| Cardiac issues | - Prolongation of the corrected QT (QTc) interval 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.
- Refer to UpToDate topics on cardiotoxicity of cancer chemotherapy agents other than anthracyclines, HER2-targeted agents, and fluoropyrimidines.
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| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
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- Assess electrolytes (especially potassium and magnesium) and liver and renal function every three weeks prior to 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 during treatment.
- Refer to UpToDate topics on cutaneous side effects of conventional chemotherapy agents.
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- More frequent anticoagulant response (INR or prothrombin time) monitoring is necessary for patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy.
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- Cardiotoxicity observed with capecitabine includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes, and cardiomyopathy. These adverse reactions may be more common in patients with a prior history of coronary artery disease.
- Refer to UpToDate topics on cardiotoxicity of non-anthracycline cancer chemotherapy agents.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - The treatment cycle should be delayed one week if the ANC is <1500/microL, or the platelet count is <75,000/microL on day 1.[1] If treatment is delayed beyond one week, reduce doses of capecitabine and oxaliplatin by 25%. Interrupt capecitabine for grade 3 or 4 hematologic toxicity during treatment (except anemia). Reduce dose of oxaliplatin by 25% for grade 3 or 4 hematologic toxicity (excluding anemia) during treatment.
|
| Neurologic toxicity | - In the original trial, for paresthesias with pain or functional impairment lasting longer than seven days, the oxaliplatin dose was decreased by 25%, and oxaliplatin was discontinued for persistence throughout a cycle.[1] The United States Prescribing Information suggests dose reduction for persistent NCI-CTC grade 2 neurosensory events (sensory alteration or paresthesias including tingling but not interfering with ADLs) and discontinuation of oxaliplatin for persistent grade 3 (objective sensory loss or paresthesias including tingling interfering with function but not ADLs) or grade 4 neurosensory events.[3]
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
|
| Hand-foot syndrome | - Interrupt capecitabine during a cycle for grade ≥2 hand-foot syndrome until recovered to grade ≤1.[1,4] Reduce subsequent capecitabine dose by 25% for grade 2 hand-foot syndrome and by 50% for grade 3 hand-foot syndrome.
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| Pulmonary toxicity | - Oxaliplatin has rarely been associated with 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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| Gastrointestinal toxicity | - Interrupt capecitabine and delay oxaliplatin for any grade 2 or worse gastrointestinal toxicity; restart treatment only after complete recovery or improvement to ≤grade 1.[3,4] After recovery, reduce the dose of oxaliplatin by 25% after the first episode of grade 3 or worse diarrhea or mucositis. Reduce the capecitabine dose by 25% in subsequent cycles at the first occurrence of grade 2 or 3 toxicity, and by 50% at the second occurrence of a given grade 2 or grade 3 toxicity or at the first occurrence of a grade 4 event. Discontinue capecitabine permanently if, despite dose reduction, a given toxicity occurs for the third time at grade 2 or grade 3, or a second time at grade 4.[5]
- NOTE: Severe diarrhea, mucositis, and myelosuppression after capecitabine should prompt evaluation for dihydropyrimidine dehydrogenase deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
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| Other toxicity (including hepatotoxicity) | - Interrupt capecitabine and delay oxaliplatin for any grade 2 or worse non-neurologic toxicity (except alopecia); restart treatment only after complete recovery or improvement to ≤grade 1.[5] Patients with grade 3 or 4 hyperbilirubinemia may resume capecitabine once toxicity has reduced to grade ≤2, but at a reduced dose.
- Reduce the dose of oxaliplatin by 25% for drug-related grade 3 or 4 nonhematologic toxicity (except hand-foot syndrome).[1]
- Reduce the capecitabine dose by 25% in subsequent cycles at the first occurrence of a grade 2 or grade 3 toxicity, and by 50% at the second occurrence of a given grade 2 or grade 3 toxicity or at the first occurrence of a grade 4 event. Discontinue capecitabine permanently if, despite dose reduction, a given toxicity occurs for the third time at grade 2 or grade 3, or a second time at grade 4.[5]
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| Doses of capecitabine omitted for toxicity are not replaced or restored; instead, the patient should resume with the next planned treatment cycle. |
| If there is a change in body weight of at least 10%, doses should be recalculated. |
