Cycle length: 21 days.
Total cycles: 6 cycles. |
| Drug | Dose and route | Administration | Given on days |
| Paclitaxel | 135 mg/m2 IV | Dilute in 500 mL NS or D5W* and administer over 24 hours.¶ | Day 1 |
| Cisplatin | 100 mg/m2 IPΔ | Dilute in one liter of NS* and infuse through the implantable peritoneal catheter via gravity drip as rapidly as possible. A second liter of saline is then administered IP as tolerated. | Day 2 |
| Paclitaxel | 60 mg/m2 IPΔ | Dilute in one liter of NS* and infuse IP via gravity drip as rapidly as possible. A second liter of saline is then administered IP as tolerated. | Day 8 |
| Pretreatment considerations: |
| Hydration | - The addition of two liters of IP NS* does not replace the need for adequate IV hydration before and after cisplatin, and the maintenance of excellent urine output. On day 2, IV pre hydration with at least one liter of NS* and a urine output of at least 100 mL/hour should be achieved before the administration of IP cisplatin to reduce the potential risk for nephrotoxicity.[2] Following the drug infusion, a second liter of IV NS* should be given, and two hours of urine output of at least 100 mL/hour should be observed before sending the patient home. Some clinicians would add 12.5 g/L of mannitol in the pre and post hydration to enhance urinary output. Supplementation with magnesium and potassium may be required depending upon the serum electrolytes. A dose of furosemide may be required if urine output is insufficient.
- Refer to UpToDate topics on intraperitoneal chemotherapy for treatment of ovarian cancer.
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| Emesis risk | - HIGH (>90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Paclitaxel may cause severe hypersensitivity reactions. Premedication regimen should include dexamethasone (either 20 mg orally 12 and 6 hours before, or 20 mg IV 30 minutes before drug administration) plus both an H1 (diphenhydramine 25 to 50 mg IV) and an H2 receptor antagonist (famotidine 20 mg IV) 30 to 60 minutes prior to paclitaxel administration. Severe infusion reactions (eg, skin rash, flushing, dyspnea, urticaria, back pain, hypotension, chest pain, tachycardia) occur primarily during the first and second infusions, typically within the first hour after the start of the infusion. Routine prophylaxis is generally not indicated prior to cisplatin treatment.[3] Management of infusion reactions and issues related to rechallenge are discussed separately.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Vesicant/irritant properties | - IV paclitaxel 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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| Dose adjustment for baseline liver or kidney dysfunction | - Patients with abnormal kidney function were excluded from the phase III clinical trial demonstrating the efficacy of this regimen.[1] Dose modifications are not required for paclitaxel in kidney insufficiency, but the dose should be adjusted for preexisting hepatic impairment.[3]
- 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 dosing of anticancer agents in adults.
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| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
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- Assess electrolytes, kidney, and liver function each cycle during treatment.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Each cycle should not begin until the WBC count is >1500/microL, platelets are >100,000/microL, and creatinine clearance is >50 mL/min.[1] In the original trial, treatment modifications for hematologic toxic effects included cycle delay, dose reduction, and use of granulocyte colony-stimulating factor (in that sequence). Dose modification was not performed if the WBC nadir was not accompanied by fever.
- 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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| Neurologic toxicity | - Both paclitaxel and cisplatin can cause neurotoxicity. In the original study, treatment was delayed in the case of grade 3 or 4 peripheral neuropathy until grade 1.[1] For severe neuropathy (grade 3 or 4) that persists for a week or longer, reduce the dose of paclitaxel by 20% for subsequent courses and substitute intravenous carboplatin for cisplatin.[3] Patients with mild neuropathy can continue to receive full cisplatin doses. 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 | - Avoidance of cisplatin-related nephrotoxicity requires close attention to volume status and adequate antiemetic control. If kidney insufficiency develops, treatment should be withheld until kidney function improves. In the original trial, treatment was postponed for a creatinine level >2.0 mg per deciliter or a CrCl of <50 mL per minute.[1] Subsequent treatment was resumed only when it rose above 50 mL/min. Tolerability of the regimen may be improved by reducing the IP cisplatin dose to 75 mg/m2.
- Refer to UpToDate topics on intraperitoneal chemotherapy for treatment of ovarian cancer.
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| Abdominal pain | - Abdominal pain, which may be worse with IP paclitaxel than after cisplatin, is frequent. Peritonitis or GI tract injury should be considered if there is guarding, rebound, nausea, vomiting, diarrhea, fever, or unexplained leucocytosis. If pain is encountered and there are no signs or symptoms to suggest peritonitis or GI tract injury, the second liter of NS* can be reduced in volume or rate of flow, or withheld. In the original trial, the dose of IP chemotherapy was reduced for CTC grade 3 abdominal pain, recurrent CTC grade 2 abdominal pain, or complications involving the intraperitoneal catheter.[1]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
