Cycle length: 28 days.
Duration: 6 months. |
| Drug | Dose and route | Administration | Given on days |
| Gemcitabine | 1000 mg/m2 IV | Dilute in 250 mL NS* (concentration no greater than 40 mg/mL) and administer over 30 minutes. | Days 1, 8, and 15 |
| Capecitabine¶ | 830 mg/m2 per dose by mouth | Twice daily (total dose 1660 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.Δ | Days 1 through 21 |
| Pretreatment considerations: |
| Emesis risk | - LOW.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Infection prophylaxis | - Primary prophylaxis with G-CSF is not indicated based on a low risk for febrile neutropenia with this regimen.[1]
- Refer to UpToDate topics on prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults.
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| Dose adjustment for baseline renal dysfunction | - A lower starting dose of gemcitabine may be needed for patients with liver impairment. A lower starting dose of capecitabine may be needed for patients with moderate renal impairment.[2]
- 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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| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
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- Assess basic metabolic panel (including serum creatinine) and liver function tests every three weeks prior to each new cycle and otherwise as indicated during treatment.
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- Monitor for diarrhea and palmar-plantar erythrodysesthesias during treatment.
- NOTE: Severe diarrhea, mucositis, and myelosuppression after capecitabine should prompt evaluation for dihydropyrimidine dehydrogenase deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic 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.
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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 nonanthracycline cancer chemotherapy agents.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Dose modifications were not presented with the abstract.[1] Other studies using gemcitabine plus capecitabine have suggested dose modifications for hematologic toxicity.[3] Do not initiate a new cycle unless neutrophils are ≥1500/microL and platelets are ≥100,000/microL. Reduce the day 8 (or day 15) gemcitabine dose by 25% for an absolute neutrophil count of 500 to 1000/microL or a platelet count of 50,000 to 100,000/microL. Decrease gemcitabine by 25% for subsequent cycles for febrile neutropenia, grade 4 hematologic toxicity lasting for more than seven days, or bleeding-associated thrombocytopenia.
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| Nonhematologic toxicity (including hepatotoxicity) | - Grade 2: For the first, second, and third occurrence, hold capecitabine therapy.[2] After resolution to grade 1 or less, resume treatment (first occurrence, no dosage adjustment; second occurrence, 75% of the starting dose; third occurrence, 50% of the starting dose).[2] For the fourth occurrence of a grade 2 toxicity, discontinue capecitabine therapy.
- Grade 3: For the first and second occurrence, hold capecitabine therapy. After resolution to grade 1 or less, resume treatment at a reduced dose (first occurrence, 75% of the starting dose; second occurrence, 50% of the starting dose). For the third occurrence of a grade 3 toxicity, discontinue capecitabine therapy.
- Grade 4: Discontinue capecitabine therapy. Alternatively, hold capecitabine therapy, and begin next treatment at 50% of the starting dose when toxicity resolves to grade 1 or less; discontinue treatment for first recurrence of grade 4 toxicity.
- Gemcitabine is commonly associated with a transient rise in serum transaminases, but these are seldom of clinical significance. There is insufficient information from clinical studies to allow clear dose recommendations in these patients.
- Patients with grade 3 or 4 hyperbilirubinemia may resume capecitabine once toxicity has reduced to ≤grade 2, but at a reduced dose.[2]
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents and chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
- Hold gemcitabine for other ≥grade 3 nonhematologic toxicity that is likely related to gemcitabine until it decreases to ≤grade 1.[4] Restart gemcitabine with a 25% dose reduction.
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| Pulmonary toxicity | - A variety of manifestations of pulmonary toxicity have been reported in patients treated with gemcitabine. Discontinue gemcitabine immediately and permanently.
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
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| Thrombotic microangiopathy | - Thrombotic microangiopathy (TMA, also sometimes called thrombotic thrombocytopenic purpura [TTP] or hemolytic uremic syndrome [HUS]) has been associated with gemcitabine in individuals who have received a large or small cumulative dose.[4] Consider the possibility of TMA if the patient develops Coombs-negative hemolysis, thrombocytopenia, renal failure, and/or neurologic findings. Management consists of drug discontinuation and supportive care, without plasma exchange, as long as there is high confidence in a drug-induced etiology rather than TTP.
- Refer to UpToDate topics on drug-induced thrombotic microangiopathy.
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| Omitted capecitabine doses for toxicity are not replaced or restored. Resume treatment with the planned next cycle. |
| If there is a change in body weight of at least 10%, doses should be recalculated. |
