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 topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
|
| 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 topic on "Prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults".
|
| 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" and "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.
|
- 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.
|
- 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".
|
- 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 topic on "Cardiotoxicity of nonanthracycline cancer chemotherapy agents".
|
| 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.
|
| 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 topic 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.
|
| 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 topic on "Pulmonary toxicity associated with antineoplastic therapy: Cytotoxic agents".
|
| 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 topic 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. |
