PHASE-II STUDY OF DOCETAXEL AND CISPLATIN IN ADVANCED NON-SMALL-CELL LUNG-CANCER

Purpose: Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatm ent of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dos e of 75 mg/m(2) of both drugs every 3 weeks for subsequent phase II st udy. Patients and Methods: Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status less than or equal to 2 and life expectancy greater than or equal to 12 weeks, wit h metastatic and/or locally advanced NSCLC proven histologically or cy tologically. Patients were not permitted to have received prior chemot herapy, extensive radiotherapy, or any radiotherapy to the target lesi on and must have had measurable disease. Concurrent treatment with col ony-stimulating factors (CSFs) or prophylactic antibiotics was not per mitted. Docetaxel (75 mg/m(2)) in 250 mL 5% dextrose was given intrave nously (IV) over 1 hour immediately before cisplatin (75 mg/m(2)) in 5 00 mL normal saline given IV over 1 hour in 3-week cycles. Premedicati on included ondansetron, dexamethasone, promethazine, and standard hyp erhydration with magnesium supplementation. Results: A total of 47 pat ients, two thirds of whom had metastatic disease, were entered onto th is phase II study. The majority of patients were male (72%) and of goo d (WHO 0 to 1) performance status (85%). All 47 patients were assessab le for toxicity and 36 were for responses Three patients were ineligib le and eight(17%) discontinued treatment because of significant toxici ty. In assessable patients, the overall objective response rate was 38 .9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable dis ease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%, Significant (grade 3/4) toxicit ies included nausea (26%), hypotension (15%), diarrhea (13%), and dysp nea mainly related to chest infection (13%), One patient experienced N ational Cancer Institute (NCI) grade 3 neurosensory toxicity after eig ht cycles. Grade 3/4 neutropenia was common and occurred in 87% of pat ients, but thrombocytopenia greater than or equal to grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium leve ls were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-relate d deaths. No neutropenic enterocolitis or severe fluid retention was r eported. Conclusion: Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combinat ion regimens.