SUPERIORITY OF SEQUENTIAL VERSUS CONCURRENT ADMINISTRATION OF PACLITAXEL WITH ETOPOSIDE IN ADVANCED NONSMALL CELL LUNG-CANCER - COMPARISON OF 2 PHASE-II TRIALS

Paclitaxel and etoposide are two chemotherapy agents with broad cytoto xic activity and different mechanisms of action and resistance, Precli nical studies of their combined cytotoxicity have yielded conflicting results, We performed two sequential Phase II trials using different s equence schedules of paclitaxel and etoposide as first-line treatment in advanced non-small cell lung cancer (NSCLC), Forty-four patients wi th stage IIIB or IV NSCLC were included between July 1995 and Septembe r 1996, All patients received etoposide at 100 mg/m(2), given as an i. v. infusion on days 1, 2, and 3, The first 20 patients (part A) also r eceived paclitaxel at 175 mg/m(2) as a 3-h infusion on day 1, immediat ely prior to etoposide, The subsequent 24 patients (part B) were given the same paclitaxel dose, but on day 4, Grade 3-4 granulocytopenia wa s seen in 70% of the patients in part A and in 37% of those in part 70 % (P = 0,04), Twenty-five % of the courses in part A and 4% of the cou rses in part B were associated with granulocyte nadir less than or equ al to 500/mu l (P = 0.00006), No responses were observed in part A, al though disease was stabilized in 14 patients (70%), In part B, there w ere two complete responses and seven partial responses, for an overall response rate of 37.5% (95% confidence interval, 21-58%), In conclusi on, toxicity and antitumor activity of the paclitaxel/etoposide combin ation may be sequence dependent. Our findings suggest that etoposide f ollowed by paclitaxel is well tolerated and has greater activity in NS CLC than concurrent administration.