| Cycle length: 42 days (6 weeks). |
| Drug | Dose and route | Administration | Given on days |
| Cisplatin | 30 mg/m2 IV | Dilute in 250 mL NS¶ and administer over 30 minutes. Do not administer with aluminum needles or IV sets. | Days 1, 8, 15, and 22 |
| Irinotecan | 65 mg/m2 IVΔ | Dilute in 500 mL D5W¶ and administer over 30 minutes immediately following cisplatin. | Days 1, 8, 15, and 22 |
| 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.
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| Emesis risk | - MODERATE.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - There is no standard prophylactic premedication regimen.
- 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.[2]
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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| Infection prophylaxis | - Routine primary prophylaxis with G-CSF is not indicated (incidence of febrile neutropenia was 7% in one study[1]). However in another study, 6 of 35 patients (17%) required hospitalization for toxicity, most commonly for neutropenic fever.[3] The decision to use G-CSF should be individualized, depending on other risk factors for prolonged neutropenia.
- 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 baseline liver or kidney dysfunction | - The optimal approach to cisplatin therapy in patients with preexisting kidney impairment is unknown. The original clinical trials required a baseline serum creatinine ≤1.5 mg/dL.[1,3] A lower starting dose of irinotecan may be needed for patients with hepatic or severe kidney impairment.[4]
- 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 nephrotoxicity and dose modification in patients with kidney impairment, conventional cytotoxic agents.
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| Diarrhea | - Irinotecan is associated with early and late diarrhea, both of which may be severe. For patients who develop abdominal cramping and/or diarrhea within 24 hours of receiving irinotecan, give atropine (0.3 to 0.6 mg IV) and premedicate with atropine during later cycles. Patients must be instructed in the early use of loperamide as a treatment for late diarrhea.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
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| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
|
- Assess basic metabolic panel (creatinine and electrolytes) and liver function tests prior to each treatment cycle.
|
- Monitor for neurotoxicity prior to each treatment cycle.
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- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
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- Patients who develop diarrhea should be closely monitored and supportive care measures (eg, fluid and electrolyte replacement, loperamide, antibiotics, etc) provided as needed. Do not retreat until resolution of diarrhea for at least 24 hours without anti-diarrheal medication.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - On each day of treatment, the white blood cell count should be ≥3000 cells/microL with absolute neutrophil count ≥1000 cells/microL and platelets ≥100,000/microL.[3] Treatment delays up to one week are permitted without dose reduction. Decrease irinotecan dose by 10 mg/m2 for hematologic toxicity resulting in treatment delay of more than two weeks, febrile neutropenia, or bleeding complications from thrombocytopenia. If hematologic toxicity causes delay of day 22 therapy, shorten treatment course to three weeks (eliminate day 22) with a two week rest period in between cycles.[3]
|
| Mucositis or diarrhea | - Delay treatment for one week if grade >2 diarrhea or mucositis on the day of treatment and further delayed if toxic effects do not diminish to grade ≤1.[1,3] Reduce subsequent irinotecan doses by 10 mg/m2 for grade 3 or 4 diarrhea or mucositis.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
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| Neurotoxicity | - 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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| Kidney toxicity | - In the original protocol, the cisplatin dose was reduced to 15 mg/m2 if serum creatinine increased to >1.7 mg/dL but remained <2.0 mg/dL.[3] The United States Prescribing Information for cisplatin recommends that subsequent doses of cisplatin be withheld until the serum creatinine is <1.5 mg/dL and/or blood urea nitrogen is <25 mg/dL.[2]
|
| Other toxicity | - For other nonhematologic toxicities, if grade 2, hold treatment until ≤grade 1; if grade 3 or 4, hold treatment until ≤grade 2.[4]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
