A PHASE I II STUDY OF PACLITAXEL (TAXOL(R)) AND CONCURRENT RADIOTHERAPY IN ADVANCED NONSMALL CELL LUNG-CANCER/

Purpose: The addition of chemotherapy to radical radiotherapy (XRT) ha s been shown to improve survival in locally advanced nonsmall cell lun g cancer (9), Consequently, different chemotherapeutic regimens in com bination with XRT are being evaluated in the treatment of this disease , Paclitaxel (TAXOL(R)) may be a valuable drug in this situation as, i n addition to a demonstrated activity in NSCLC, it has been shown to e nhance the effect of radiation on cell lines in vitro. Methods and Mat erials: Seventeen patients were enrolled onto a Phase I/II trial to de termine the maximum tolerated dose of paclitaxel given by a 3-h infusi on every 2 weeks throughout a 6-week course of XRT, 60 Gy in 30 daily fractions, in patients with Stage III NSCLC and then to describe the r esponse rate of this combination in an expanded cohort of patients tre ated at the recommended phase II dose, Three patients were entered at each dose level (45, 90, 120, and 135 mg/m(2)), except for the 120 mg/ m(2) dose level, which was expanded to nine patients. Results: The dos e limiting toxicity was neutropenia-two of three patients treated at t he 135 mg/m(2) level experienced Grade 3 neutropenia on day 15, which precluded administration of scheduled chemotherapy, Esophagitis was mi ld to moderate, and although profound lymphopenia was observed at all dose levels, there was no evidence of associated opportunistic infecti ons, Of the nine patients treated at the recommended Phase II dose of 120 mg/m(2), there were one complete and six partial responses (respon se rate 78%). Conclusion: The combination of XRT, 60 Gy in 6 weeks and paclitaxel, 120 mg/m(2)q 2 weeks, can be safely given to patients wit h NSCLC, and although it demonstrates activity in this situation, cons ideration should be given to the addition of other agents, such as pla tinum compounds. (C) 1997 Elsevier Science Inc.