| Cycle length: Every 21 days, for a maximum of six cycles. |
| Drug | Dose and route | Administration | Given on days |
| Gemcitabine | 1200 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 and 8 |
| Cisplatin | 75 mg/m2 IV | Dilute in 250 mL NS and administer over 60 minutes. Do not administer with aluminum needles or sets. | Day 1 |
| Pretreatment considerations: |
| Hydration | - IV fluid to establish a urine flow of at least 100 mL/hour for at least two hours prior to and two hours after cisplatin administration.
- Refer to UpToDate topics on cisplatin nephrotoxicity.
|
| Emesis risk | - Day 1: HIGH;
Day 8: LOW. - Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| 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 hematopoietic growth factors is not recommended (risk of neutropenic fever is approximately 4%).
- 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.
|
| 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.[2] 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.
|
- Electrolytes, kidney, and liver function weekly during treatment.
|
- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Each cycle should not begin until the WBC count is >3000 cells/microL and platelet count is >100,000/microL.[1] Gemcitabine should be withheld on day 8 if the WBC count is <2000 cells/microL or platelets are <50,000/microL.[1] This is consistent with the United States Prescribing Information that recommends to hold gemcitabine for an ANC <500 cells/microL and platelets <50,000/microL.[3]
|
| Neurologic toxicity | - Neuropathy usually is seen with cumulative doses of cisplatin >400 mg/m2, although there is marked interindividual variation.
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
|
| 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.[3] 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.
|
| 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.
|
| Severe non-hematologic toxicity | - Gemcitabine and cisplatin should be withheld or doses decreased depending on clinical judgement.
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
