Cycle length: 21 days.
Duration of therapy: Maximum of 8 cycles. |
| Drug | Dose and route | Administration | Given on days |
| Cisplatin | 25 mg/m2 IV daily | Dilute in 1000 mL NS* with 20 mEq (20 mmol) of potassium chloride and 2 grams (8 mmol) of magnesium sulfate and administer over 60 minutes. Do not administer with aluminum needles or IV sets. Follow infusion with 500 mL NS* over 30 minutes. | Days 1 and 8 |
| Gemcitabine | 1000 mg/m2 IV daily | Dilute in 250 mL NS* (concentration no more than 40 mg/mL) and administer over 30 minutes after cisplatin and IV fluid. | Days 1 and 8 |
| Pretreatment considerations: |
| Hydration | - Pretreatment hydration with 1 to 2 L of fluid infused during and following each dose of cisplatin.[2]
- Refer to UpToDate topics on cisplatin nephrotoxicity.
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| Emesis risk | - HIGH (>90%).¶
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Routine prophylaxis is not indicated for cisplatin or gemcitabine.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Vesicant/irritant properties | - Cisplatin 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 | - The exact incidence of febrile neutropenia was not reported; however, 25% had grade 3 or 4 neutropenia.[1] Decisions about primary prophylaxis with G-CSF should be individualized according to current guidelines.
- Refer to UpToDate topics 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 | - The optimal approach to cisplatin therapy in patients with pre-existing renal impairment is unknown. Patients with a calculated glomerular filtration rate <45 mL/min were excluded from the trial.[1] 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; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents; and chemotherapy-related nephrotoxicity and dose modification in patients with renal insufficiency.
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| Monitoring parameters: |
- Obtain CBC with differential and platelet count and assess serum electrolytes and renal function prior to each treatment.
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- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
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- Assess pulmonary function at baseline and as clinically indicated.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - A new cycle of treatment should not start until neutrophils recover to >1500/microL and platelets recover to >100,000/microL. Intracycle dose reduction: Omit day 8 chemotherapy for neutrophil count <500/microL or platelet count <50,000/microL. Reduce day 8 dose of gemcitabine by 25% for neutrophil count >500 but <1000/microL, or platelet count >50,000 but <100,000/microL.
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| 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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| Pulmonary toxicity | - A variety of manifestations of pulmonary toxicity have been reported with gemcitabine. Discontinue gemcitabine immediately and permanently.
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
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| Hepatotoxicity | - 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.[3]
- 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.
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| Neurologic toxicity | - Neuropathy usually is seen with cumulative doses of cisplatin >400 mg/m2, although there is marked interindividual variation. Patients with mild neuropathy can continue to receive full cisplatin doses. However, if the neuropathy interferes with function, the risk of potentially disabling neurotoxicity must be weighed against the benefit of continued treatment.
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
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| Nephrotoxicity | - Hold cisplatin until serum creatinine <1.5 mg/dL and/or BUN <25 mg/dL.[2] For grade ≥2 nephrotoxicity during treatment (creatinine >1.5 times normal value despite adequate hydration), CrCl should be determined prior to next cycle, and cisplatin dose reduced if <60 mL/min.[2]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
