PHASE-I STUDY OF PACLITAXEL AND ETOPOSIDE FOR METASTATIC OR RECURRENTMALIGNANCIES

The authors define the dose-limiting toxicities and the recommended ph ase LI doses of paclitaxel combined with etoposide, without and with f ilgrastim support. Patients with advanced solid tumors were eligible i f they had a performance status of 0 to 2 and normal renal, hepatic, a nd bone marrow function. Patients with cardiac arrhythmias or congesti ve heart failure requiring medical therapy were excluded. Prior radiat ion was allowed only if it involved less than 30% of the marrow-contai ning skeleton. The dose of etoposide was fixed at 100mg/m(2)/d for 3 d ays beginning on day 1. Paclitaxel was administered over 3 hours on da y 4. The dose of paclitaxel was escalated until the maximum tolerated dose (MTD), without and with filgrastim 5 mu g/kg (Or 300 mu g total d ose) subcutaneously beginning on day 5, was reached, Treatment cycles were repeated every 21 days. Of 39 patients entered, 37 were evaluable for toxicity and 30 for response. The principal toxicity was neutrope nia. Without filgrastim, the MTD of paclitaxel was 150 mg/m(2). With f ilgrastim, the dose of paclitaxel was escalated to 250 mg/m(2) in comb ination with etoposide 100 mg/m(2) One episode of pulmonary toxicity w as observed. Five patients responded: two with previously treated non- small-cell lung cancer (NSCLC), two with refractory small-cell lung ca ncer (SCLC), and one with refractory germ-cell tumor (GCT). We conclud e that paclitaxel and etoposide can be given in combination at clinica lly relevant doses with filgrastim support. In this phase I trial, a d ose of paclitaxel of 200 mg/m(2) on day 4 and etoposide at 100 mg/m(2) /d on days 1-3, with filgrastim 5 mu g/kg beginning on day 5, was foun d to be well tolerated, and can be recommended for future studies. Wit hout filgrastim, a paclitaxel dose of 150 mg/m(2) with the same dose o f etoposide can also be recommended.