Drug Interactions between cisplatin and Taxol

ADJUST DOSING INTERVAL: In a phase I trial using escalating doses of paclitaxel and cisplatin as sequential infusions, myelosuppression was more profound when paclitaxel was administered after cisplatin than when cisplatin was administered after paclitaxel. Pharmacokinetic data from these patients demonstrated a 33% decrease in paclitaxel clearance when it was administered following cisplatin.

MONITOR: The risk of neurotoxicity including peripheral neuropathy may be increased during concomitant use of paclitaxel and cisplatin. These agents are individually neurotoxic and may have additive effects during coadministration. In a study of patients with first-line ovarian carcinoma, the group treated with paclitaxel 175 mg/m2 given by 3-hour infusion plus cisplatin 75 mg/m2 had an increased incidence and severity of neurotoxicity compared to the group that received a regimen containing cyclophosphamide and cisplatin (87% vs. 52%, with 21% vs. 2% severe, respectively). In another first-line ovarian carcinoma study, the incidence of neurotoxicity--specifically peripheral neuropathy--was similar in patients treated with paclitaxel 135 mg/m2 given by 24-hour infusion plus cisplatin 75 mg/m2 and those who received a regimen containing cyclophosphamide plus cisplatin (25% vs. 20%, with 3% vs. 0% severe, respectively). A cross-study comparison suggests that when paclitaxel is given in combination with cisplatin 75 mg/m2, severe neurotoxicity is more frequent at a paclitaxel dose of 175 mg/m2 given by 3-hour infusion (21%) than at a dose of 135 mg/m2 given by 24-hour infusion (3%). In patients with non-small cell lung cancer (NSCLC), administration of paclitaxel followed by cisplatin resulted in a greater incidence of severe neurotoxicity than that reported for patients with ovarian or breast cancer treated with single-agent paclitaxel. Severe neurosensory symptoms were noted in 13% of NSCLC patients receiving paclitaxel 135 mg/m2 by 24-hour infusion followed by cisplatin 75 mg/m2 and 8% of NSCLC patients receiving cisplatin/etoposide.

MANAGEMENT: Paclitaxel should be given before cisplatin when used in combination. Peripheral blood cell counts and neurologic examination should be performed regularly, and patients should be advised to contact their physician if they develop signs and symptoms of myelosuppression such as pallor, dizziness, fatigue, lethargy, fainting, easy bruising or bleeding, or signs of infection such as fever, chills, sore throat, body aches, and other influenza-like symptoms. Patients should also seek medical attention if they experience signs and symptoms of neuropathy such as visual disturbances and burning, tingling, pain, or numbness in the hands and feet. Consideration should be given to dosage reductions or immediate discontinuation of these medications in patients who develop severe myelosuppression or peripheral neuropathy.

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