Dose-finding study of paclitaxel (Taxol) plus cisplatin in patients with non-small cell lung cancer.

We present preliminary results of a study undertaken in previously untreated patients with non-small cell lung cancer to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when administered as a 3-hour intravenous infusion in combination with cisplatin every 3 weeks; to evaluate the nature, frequency, severity, and duration of adverse events associated with this drug combination; and to evaluate the combination's antitumor efficacy. Thus far, we have treated 10 patients with cisplatin (100 mg/m2) and increasing doses of paclitaxel (135, 170, and 200 mg/m2). Among nine evaluable patients, four partial responses have been obtained, disease in three patients progressed after three courses, and no changes were seen in one patient. One patient had two cardiac arrests within 8 days of the onset of therapy, from which he recovered; he died 1 month later of massive hemoptysis. Thrombocytopenia was not seen in these patients, and neutropenia (< 1,000 granulocytes/microL) was seen in only three patients. Infections were seen in these patients and were manageable in all cases. Other toxicities consisted mainly of World Health Organization grades II and III alopecia and nausea and/or vomiting. No grade III nephrotoxicity, neurotoxicity, hypersensitivity, mucositis, or infection was seen in this series after one to three courses of chemotherapy; one patient presented with grade IV cardiotoxicity 6 days after the onset of therapy. So far, the maximum tolerated dose of the cisplatin/paclitaxel combination has not been reached; however, definitive conclusions await the full treatment of additional patients. Moreover, the possibility of cumulative and delayed toxicity must be evaluated after a sufficient duration of follow-up in adequate numbers of patients.