1084 Interim results of a phase II trial of docetaxel in combination with cisplatin in patients with metastatic or locally advanced non-small cell lung cancer (NSCLC)

Abstract

Docetaxel (Taxotere^®; T), a semi-synthetic taxoid has considerable single agent activity in NSCLC with a response rate of 38% (Francis <i>et al.</i>, JCO12; 1232, 1994). We recently reported the results of a phase I trial of T in combination with cisplatin (P) in patients (pts) with metastatic or locally advanced NSCLC. For phase II trials, the recommended dose of each agent administered as a 1hr infusion was 75mg/m² <i>(Ann. Oncol.</i> 5; P773, 1994). Hydration was started 2hrs prior to T which was given immediately prior to P and ended 22hrs post P. Ondansetron and dexamethasone were given as antiemetics. Cycles were repeated each 21 days. Eligibility included locally advanced/metastatic NSCLC, no prior chemotherapy, measurable disease, age 18–75 yrs, WHO performance status (PS) 0–2 and adequate bone marrow, hepatic and renal function. CSF's or prophylactic antibiotics were not permitted. Interim results, as analysed on 9/3/95 are reported. Baseline characteristics for the 47 eligible patients (2 pts with Stage 1 disease were excluded from response analysis) were median age 60 (range 36–74) years, PS 1/2 of 61%/22% and Stage III/IV, 37%/63% pts respectively. All pts were evaluable for toxicity but only eligible pts completing 2 cycles of chemotherapy were evaluable for response. In 36 evaluable pts, the partial response (PR) rate was 33% (12/36 pts), SD 44% (16/36 pts) and PD 22% (8/36 pts). Of the 12 PR's, 6 have been confirmed on subsequent CT scans. Grade 4 toxicities included febrile neutropenia (3 pts), neutropenia (31 pts) and diarrhea (5 pts). Grade 3 or 4 nausea/vomiting was seen in 10 pts. Other toxicities requiring dose reductions or discontinuation of study medication included cardiac abnormalities (2 pts) and fluid retention (2 pts). There were 9 hypersensitivity reactions. There was 1 toxic death (infection and neutropenia). Although significant toxicities were observed, these were manageable. Final results will be presented. The combination of docetaxel and cisplatinum has significant activity in NSCLC although does not appear to be substantially better than T alone. Toxicity may preclude phase III evaluation.