Drug Interactions between carboplatin and sorafenib

CONTRAINDICATED: Coadministration of sorafenib in combination with carboplatin and paclitaxel has been associated with an increased risk of death in patients with squamous cell lung cancer. The exact cause has not been identified, and no significant pharmacokinetic changes in any of the three drugs were observed in two phase I clinical studies. A randomized, placebo-controlled trial consisting of 926 chemotherapy-naive patients with unresectable stage IIIB or IV non-small cell lung cancer was stopped early because overall survival was not improved with the addition of sorafenib to a standard carboplatin and paclitaxel regimen. In a subset analysis of the 219 patients with squamous cell carcinoma, increased mortality and decreased progression-free survival were observed with the addition of sorafenib compared to carboplatin and paclitaxel alone. Data in the treatment of other malignancies are limited. Serious toxicities led to the early termination of another study using the same combination to treat advanced ovarian cancer. The study enrolled just 4 patients, but all were ultimately excluded from protocol due to adverse events. Three had life-threatening events (cardiac output failure, myocardial infarction, anastomotic leak), and all required a dosage reduction of sorafenib due to toxicity. In a phase III study of patients with advanced melanoma, sorafenib added to carboplatin and paclitaxel did not increase response rates or progression-free survival as second-line treatment over the two agents alone, but there was an increased incidence of dermatologic adverse events and thrombocytopenia.

MANAGEMENT: The concomitant use of sorafenib with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer. Caution may be advisable when this combination is used in other malignancies.