Cycle length: Every 21 days for a maximum of four cycles. |
Drug | Dose and route | Administration | Given on days |
Gemcitabine | 1000 mg/m2 IV | Dilute in 250 mL NS* (concentration no more than 40 mg/mL) and administer over 30 to 60 minutes. | Days 1 and 8 |
Carboplatin | AUC¶ = 5 mg/mL × min IV | Dilute in 250 mL NS* and administer over 30 minutes. | Day 1 |
Pretreatment considerations: |
Emesis risk | - MODERATE on day 1 and LOW on day 8.Δ
- Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
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Vesicant/irritant properties | - Carboplatin is an irritant.
- Refer to UpToDate topic on "Extravasation injury from chemotherapy and other non-antineoplastic vesicants".
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Infection prophylaxis | - The incidence of neutropenic infections was reported to be 9% but may be higher in patients 75 years of age or older.[1] Decisions about primary prophylaxis with hematopoietic growth factors should be individualized according to current guidelines.
- Refer to UpToDate topic 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 | - Each carboplatin dose should be calculated based upon renal function by use of the Calvert formula.¶ A lower starting dose of gemcitabine may be needed for patients with liver impairment.
- 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 "Dosing of anticancer agents in adults".
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Monitoring parameters: |
- CBC with differential and platelet count on days 1 and 8 of each cycle during treatment.
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- Electrolytes, renal, and liver function on day 1 of each cycle.
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Suggested dose modifications for toxicity:◊ |
Myelotoxicity | - Chemotherapy should be delayed for one week if the ANC is <1000/microL and/or the platelet count is <75,000/microL prior to the start of each cycle. Doses for subsequent cycles are reduced by 25% if the ANC is 1000 to 1499/microL or platelets are 75,000 to 99,000/microL on day 22 after the preceding cycle, or if the nadir ANC was <500/microL. A 50% dose reduction should be considered if the platelet nadir is <50,000/microL. Consider discontinuing therapy if a patient qualifies for a third dose reduction or a cycle is delayed by more than 21 days.
- Omissions or reductions of the gemcitabine dose on day 8 of a cycle are allowed and are based upon the same criteria as on day 1. Dose reductions should be maintained for subsequent cycles.[1]
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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.[2] 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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Pulmonary toxicity | - A variety of manifestations of pulmonary toxicity have been reported. Discontinue gemcitabine immediately and permanently.
- Refer to UpToDate topic on "Pulmonary toxicity associated with antineoplastic therapy: Cytotoxic agents".
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Other nonhematologic toxicity§ | - Creatinine clearance should be ≥45 mL/min and grade 3 or 4 toxicities should be resolved prior to beginning therapy. A delay in therapy by one week should be considered if toxicities are not resolved or the creatinine clearance ≤45 mL/min. It is recommended that subsequent cycles be dose reduced by 25% if the patient has grade 3 or 4 toxicity (excluding grade 3 or 4 mucositis, in which a 50% dose reduction is warranted) and discontinued if a patient qualifies for a third dose reduction or a cycle is delayed by more than 21 days.
- Omissions or reductions of the gemcitabine dose on day 8 of a cycle are allowed. Dose reductions should be maintained for subsequent cycles.[1]
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If there is a change in body weight of at least 10%, doses should be recalculated. |