Cycle length: 21 days. |
Drug | Dose and route | Administration | Given on days |
Gemcitabine* | 1000 mg/m2 IV | Dilute in 250 mL normal saline (concentration no greater than 40 mg/mL) and administer over 30 minutes. | Days 1 and 8 |
Capecitabine¶ | 650 mg/m2 per dose by mouth | Twice daily (total dose 1300 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 14 |
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 (incidence of neutropenic fever = 2%) for this regimen.[2]
- Refer to UpToDate topics on prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults.
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Dose adjustment for baseline liver or renal dysfunction | - A lower starting dose of gemcitabine may be needed for patients with liver impairment.[3] A lower starting dose of capecitabine may be needed for patients with moderate renal impairment.[4]
- 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.
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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 | - This regimen should not be initiated unless neutrophils are ≥1500/microL and platelets are ≥100,000/microL.[1,2] Reduce the day 8 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.[2] Decrease gemcitabine by 25% for subsequent cycles for febrile neutropenia, grade 4 hematologic toxicity lasting for more than seven days, or bleeding-associated thrombocytopenia.[2]
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Nonhematologic toxicity (including hepatotoxicity) | - In the initial protocol, capecitabine was interrupted for ≥grade 2 nonhematologic toxicity (except alopecia) that was likely related to capecitabine until it decreased to ≤grade 1.[2] Decrease subsequent capecitabine dose by 25% for ≥grade 3 nonhematologic toxicity or recurrent grade 2 toxicity (except alopecia).
- The United States Prescribing Information also contains recommendations for capecitabine dose reduction based upon toxicity[4].
- Grade 2: For the first, second, and third occurrence, hold capecitabine. 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). 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.
- Patients with grade 3 or 4 hyperbilirubinemia may resume capecitabine once toxicity has reduced to grade ≤2, but at a reduced dose.[4]
- 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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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.[3] 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. |