PHASE-I TRIAL OF DOCETAXEL AND CISPLATIN IN PREVIOUSLY UNTREATED PATIENTS WITH ADVANCED NON-SMALL-CELL LUNG-CANCER

Purpose: To determine the maximum-tolerance does (MTDs), principal tox icities, and pharmacokinetics of the combination of docetaxel and cisp latin administered every 3 weeks to patients with advanced non-small-c ell lung cancer (NSCLC) who have not received prior chemotherapy and t o recommend a dose of phase II studies. Patients and methods: Patients with advanced NSCLC and performance status 0 to 2 who have not receiv ed prior chemotherapy received docetaxel over 1 hour followed by cispl atin over 1 hour with hydration. Dose levels studied were (docetaxel/c isplatin) 50/75, 75/75, 75/100, and 100/75 mg/m(2) repeated every 3 we eks. Colony-stimulating factor (CSF) support was not used. Pharmacokin etics of docetaxel and cisplatin were studied in the first cycle of th erapy. Most patients (79%) had metastic disease or intrathoracic recur rence after prior radiation and/or surgery. Results: Of 24 patients en tered, all were assessable for toxicity and 18 for response. The MTD s chedules were docetaxel 75 mg/m(2) with cisplatin 100 mg/m(2) (dose-li miting docetaxel toxicities [DLTs] in five of six patients), and docet axel 100 mg/m(2) with cisplatin 75 mg/m(2) (DLTs in two of two patient s, including one fatal toxicity). Limiting toxicities were febrile neu tropenia and nonhematologic, principally diarrhea and renal. Two patie nts had neutropenic enterocolitis. Pharmacokinetics of both drugs were consistent with results from single-agent studies, which suggests no major pharmacokinetic interaction. Neutropenia was related to docetaxe l area under the plasma concentration-versus-time curve (AUG). An alte rnative schedule was investigated, with cisplatin being administered o ver 3 hours commencing 3 hours after docetaxel, but toxicity did not a ppear to be less. Independently reviewed responses occurred in eight o f 18 patients (44%; 95% confidence interval, 22% to 69%), most followi ng 75 mg/m(2) of both drugs. Conclusion: Docetaxel 75 mg/m(2) over 1 h our followed by cisplatin 75 mg/m(2) over 1 hour is recommended for ph ase II studies. The responses seen in this phase I study suggest a hig h degree of activity of this combination in previously untreated advan ced NSCLC. (C) 1997 by American Society of Clinical Oncology.