A PHASE-I TRIAL OF PACLITAXEL PLUS CARBOPLATIN IN UNTREATED PATIENTS WITH ADVANCED NONSMALL CELL LUNG-CANCER

This Phase I study was designed to determine the maximally tolerated d oses of paclitaxel (given as an outpatient 3-h infusion) plus carbopla tin in advanced, untreated nonsmall cell lung cancer. Secondary object ives were to determine the response rate, response duration, and survi val. Fifty-six patients were accrued, and all were evaluable for toxic ity; 50 patients were assessable for response. Paclitaxel doses ranged from 135-250 mg/m(2), whereas carboplatin dosing started at 250 mg/m( 2) and was escalated to 400 mg/m(2). Patients received therapy on day 1 every 21 days for a maximum of six cycles. Prophylactic granulocyte colony-stimulating factor was not given initially but was allowed if g rade 4 neutropenia developed. Neutropenia was the major toxicity obser ved (41% of patients; 16% of courses) and was dose related. However, f ebrile neutropenia was uncommon (4%), and no patient receiving growth factor developed subsequent grade 4 neutropenia. Only one patient deve loped grade 4 thrombocytopenia. No grade 4 neuropathy or grade 3 or 4 myalgias/arthralgias were reported. Grade 4 allergic reactions occurre d in three patients (5%), and two patients sustained grade 4 cardiac t oxicity (4%). Partial responses were observed in 13 of 50 patients (26 %). One of 13 patients (8%) receiving paclitaxel at 135 mg/m(2) and ca rboplatin (250-350 mg/m(2)) responded versus 12 of 37 patients (32%) r eceiving paclitaxel doses greater than or equal to 175 mg/m(2) with ca rboplatin doses of 350-400 mg/m(2). The median time to progression, me dian survival, and 1-year survival rates seemed to be dose related, wi th median times to progression of 6, 18, and 27 weeks; median survival of 13, 29, and 39 weeks; and 1-year survival sates of 15, 28, and 41% for the 135, 175-200, and 225-250 mg/m(2) groups. We conclude that fu ll doses of both paclitaxel and carboplatin can be given safely on an outpatient basis with 3-h paclitaxel infusions. Neutropenia is the mos t common toxicity; response rates and survival at higher dose levels w ere encouraging. Phase III trials to determine the optimal dose and in fusion schedule of this combination are warranted, as are trials to co mpare paclitaxel/carboplatin to other active single agents or combinat ion regimens.