Outcome of patients with a performance status of 2 in Eastern cooperative oncology group study E1594 - A phase III trial in patients with metastatic nonsmall cell lung carcinoma

BACKGROUND. Eastern Cooperative Oncology Group (ECOG) Study E1594 compared paclitaxel and cisplatin with three newer chemotherapy doublets in the trea tment of patients with advanced nonsmall cell lung carcinoma (NSCLC). The a ccrual of patients with an ECOG performance status (PS) of 2 was discontinu ed due to a perceived rate of unacceptable toxicity. METHODS. Patients were stratified by PS and randomized to one of the follow ing treatments: 1) paclitaxel (135 mg/m(2)) over 24 hours with cisplatin (7 5 mg/m(2)) on a 21-day cycle; 2) cisplatin (100 mg/m(2)) with gemcitabine ( 1 g/m(2)) on Days 1, 8, and 15 on a 28-day cycle; 3) cisplatin (75 mg/m(2)) with docetaxel (75 mg/m(2)) on a 21-day cycle; and 4) paclitaxel (225 mg/m (2)) over 3 hours with carboplatin (area under the curve, 6). All tests of statistical significance were two-sided. RESULTS. Sixty-eight patients with an ECOG PS of 2 were enrolled, and 64 pa tients were evaluable for toxicity and response. Fifty-six percent of 64 ev aluable patients were male, and 81% had Stage IV disease. Grade 3-4 hematol ogic toxicities occurred in > 50% of the patients in each treatment group. Nonhematologic Grade 3-4 toxicities occurred significantly less often in th e paclitaxel and carboplatin arm (P = 0.0032). The overall rate of toxicity did not differ significantly from the rate of toxicity in the PS-0 or PS-1 cohorts. There were 5 deaths (7.35%) among 68 patients with a PS of 2 duri ng therapy; however, only 2 of those deaths were attributed to therapy. The overall response rate for the 64 evaluable patients was 14%. The overall m edian survival of all 68 patients with a PS of 2, as determined by an inten t-to-treat analysis, was 4.1 months. CONCLUSIONS. Patients with advanced NSCLC and a PS of 2 experienced a large number of adverse reactions and overall poor survival. A corn parison with patients with a PS of 0-1 suggests that these events and the shorter survi val were related to disease process rather than treatment. Alternative stra tegies need to be explored with therapy specifically tailored for this grou p of patients. (C) 2001 American Cancer Society.