PHASE-II STUDY OF GEMCITABINE (2',2'-DIFLUORODEOXYCYTIDINE) GIVEN AS A TWICE WEEKLY SCHEDULE TO PREVIOUSLY UNTREATED PATIENTS WITH NONSMALL CELL LUNG-CANCER

A variety of new drugs have been tested in non-small cell lung cancer (NSCLC), but overall the response rates obtained are low and of short duration [1]. Gemcitabine, 2',2'-difluorodeoxycytidine, a pyrimidine antimetabolite, was developed as a new deoxycytidine analogue [2]. Preclinically the compound has shown a broad spectrum of antitumor activity in tumor models and clinically in different solid tumors. Gemcitabine is a phase specific drug and a phase II study was undertaken in NSCLC to see whether a more frequent dosing would increase the response rate (26%; 95% CI: 14%-40%) already observed in a previous study of gemcitabine given once weekly to a similar patient population [3]. schedule remained fixed, and doses that could not be given on time were not administered at all. Based on the judgement of the treating physician patients who developed grade 3 non-hematologic toxicity could have their therapy reduced by 50% or withheld. Patients who developed grade 4 non-hematologic toxicity were removed from the study unless they were responding, in which case a 50% dose reduction was given when the toxicity had resolved. Subsequent doses were escalated by 10% in patients who had completed one course of therapy provided hematologic and non-hematologic toxicity was less than or equal to grade 1. A 10% dose escalation was allowed in all subsequent cycles if tolerated. Postponement for three weeks or more due to toxicity caused discontinuation of treatment. Response to therapy was assessed every four weeks by chest x-ray, whereas CT-/ultrasound-scanning was repeated every other course. Response data were reviewed independently by external experts.