Cycle length: 28 days.
Total cycles: Maximum of 6 cycles.* |
| Drug | Dose and route | Administration | Given on days |
| Gemcitabine | 1000 mg/m2 IV | Dilute in 250 mL normal saline (NS) (concentration no more than 40 mg/mL) and administer over 30 to 60 minutes. | Days 1, 8, and 15 |
| Cisplatin | 70 mg/m2 IV | Dilute in 250 mL NS and administer over two hours.¶ Do not administer with aluminum needles or sets. | Day 2 |
| Pretreatment considerations: |
| Hydration | - Due to the potential for nephrotoxicity associated with cisplatin, pretreatment hydration with 1 to 2 L of fluid is recommended prior to cisplatin administration; adequate post hydration and urinary output (>100 mL/hour) should be maintained for 24 hours after administration.[2]
- Refer to UpToDate topics on cisplatin-induced nephrotoxicity.
|
| Emesis risk | - LOW (10 to 30% risk of emesis) on days 1, 8, and 15, and HIGH (>90% risk of emesis) on day 2.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Routine prophylaxis not indicated.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
|
| 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.
|
| Infection prophylaxis | - Primary prophylaxis with granulocyte colony stimulating factors is not justified (estimated risk of febrile neutropenia <20%[1]).
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
|
| Dose adjustment for preexisting baseline liver or kidney dysfunction | - The optimal approach to cisplatin therapy in patients with preexisting kidney impairment is unknown. Such patients were excluded from the original trial.[1] A lower starting dose of gemcitabine may be needed for patients with liver impairment.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with kidney impairment, conventional cytotoxic agents; 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.
|
| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
|
- Assess electrolytes, kidney, and liver function weekly during treatment.
|
- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
|
- Assess changes in neurologic function prior to each cycle.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Each cycle should not begin until the WBC is ≥3000/microL and platelet count is ≥100,000/microL.[1] Gemcitabine should be withheld on day 8 and/or day 15 of the scheduled treatment if the WBC is <2000/microL or the platelet count is <50,000/microL.[1] If the day 8 or 15 dose of gemcitabine is omitted, the treatment cycle may be shortened to 21 days.
|
| 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.
|
| Pulmonary toxicity | - A variety of manifestations of pulmonary toxicity have been reported. Discontinue gemcitabine immediately and permanently.
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
|
| 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.
|
| Nephrotoxicity | - Hold cisplatin until serum creatinine <1.5 mg/dL and/or blood urea nitrogen <25 mg/dL. For grade ≥2 nephrotoxicity during treatment (creatinine >1.5 times normal value despite adequate hydration), creatinine clearance should be determined prior to next cycle, and cisplatin dose reduced if <60 mL/min.
|
| 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. Consider the possibility of TMA if the patient develops Coombs-negative hemolysis, thrombocytopenia, kidney 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.
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
