| Cycle length: 21 days × 8 cycles. |
| Drug | Dose and route | Administration | Given on days |
| Oxaliplatin* | 130 mg/m2 IV | Dilute in 500 mL D5W¶ hrd administer over two hours. Shorter oxaliplatin administration schedules (eg, 1 mg/m2 per minute) appear to be safe.[3] | Day 1 |
| CapecitabineΔ | 1000 mg/m2 per dose, by mouth | Twice daily (total dose 2000 mg/m2 per day). 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.◊ | Day 1 through 14 |
| 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 topic 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 | - While rates of febrile neutropenia were not reported in the primary reference for this regimen in the adjuvant setting, the rate of grade 3 or 4 neutropenia was 22%, so the decision to use primary prophylaxis with granulocyte-colony stimulating factors should not be routine but individualized based on additional risk factors.[1,2]
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy induced neutropenia and conditions other than leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
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| Dose adjustment for 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.
|
| 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 QTc 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.
|
| Pulmonary issues | - Oxaliplatin has rarely been associated with pulmonary toxicity.[4]
- Refer to UpToDate topics on cardiotoxicity of cancer chemotherapy agents other than anthracyclines, HER2-targeted agents, and fluoropyrimidines and pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
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| Monitoring parameters: |
- Obtain CBC with differential and platelet count prior to each treatment.
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- Assess electrolytes (particularly 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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- Assess cardiac function at baseline and then as clinically indicated.
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- Monitor for diarrhea and palmar-plantar erythrodysesthesias during treatment.
- Refer to UpToDate topics on enterotoxicity of chemotherapy agents and 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.
|
- 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 cancer chemotherapy agents other than anthracyclines, HER2-targeted agents, and fluoropyrimidines.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - While the primary reference did not report the protocol-specified alterations for treatment-related toxicity, guidelines are available from trials of this same CAPOX regimen in patients with advanced disease.[5,6] A new cycle of treatment should not start until neutrophils recover to >1500/microL and platelets recover to >100,000/microL.[6,7] Some clinicians will initiate a new cycle of therapy if the platelet count is >75,000/microL. Interrupt capecitabine until the next cycle begins for any grade 2 or worse hematologic toxicity and delay treatment until complete recovery or improvement to ≤grade 1. After recovery, reduce doses of both drugs by 20% for febrile neutropenia in the preceding cycle.[5]
|
| Neurologic toxicity | - Reduce the dose of oxaliplatin by 25% for persistent (14 days or longer) paresthesia or temporary (7 to 14 days) painful paresthesia or functional impairment.[6] For persistent painful paresthesia or functional impairment omit oxaliplatin until recovery and if it completely resolves, restart at 50% of dose.[6] Discontinue if toxicities recur despite dose reduction.
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
|
| Gastrointestinal toxicity | - Interrupt capecitabine until the initiation of the next cycle and delay oxaliplatin for any grade 2 or worse gastrointestinal toxicity; restart treatment only after complete recovery or improvement to ≤grade 1. Reduce the capecitabine dose by 25% in subsequent cycles at the first occurrence of grade 2 gastrointestinal toxicity, or grade 3 or 4 toxicity including mucositis.
- NOTE: Severe diarrhea, mucositis, and myelosuppression after capecitabine should prompt evaluation for dihydropyrimidine dehydrogenase deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
|
| 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.[5]
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
|
| 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.[6] Patients with grade 3 or 4 hyperbilirubinemia may resume capecitabine once toxicity has reduced to grade ≤2, but at a reduced dose.[7]
- Reduce the dose of oxaliplatin by 25% for any drug-related grade 3 toxicity other than that described above.
- Reduce the capecitabine dose by 20 to 30% in subsequent cycles for grade 2 or grade 3 toxicity (including hand-foot syndrome) during a preceding cycle.[5] Discontinue capecitabine permanently if, despite dose reduction, a given toxicity occurs for the fourth time at grade 2, third time at grade 3, or a second time at grade 4.[7]
- For transient renal insufficiency in the preceding cycle, reduce doses of both drugs.
|
| Doses of capecitabine that are omitted for toxicity should not be replaced. The patient should resume the planned treatment cycles at the modified dose. |
| If there is a change in body weight of at least 10%, doses should be recalculated. |
