ABSTRACT
BACKGROUND: Although 30-min gemcitabine infusion has become the standard administration, pre-clinical and clinical studies have suggested the possibility that an infusion rate of 10 mg/m(2) per minute may be more effective. The main objective of this study was to investigate whether the pursuance of gemcitabine, administered at a prolonged infusion rate, was able to convert stable disease to objective response after two or three cycle of standard administration. The secondary end-point was the evaluation of the new schedule toxicity. PATIENTS AND METHODS: Thirty-eight patients, with stage IIIA-B and IV NSCLC already treated by two or three cycles of 30-min gemcitabine infusion, alone or in combination with cisplatin, were enrolled: 26 patients (aged <70 years) were treated with cisplatin 80 mg/m(2) on day 1 plus gemcitabine 1200 mg/m(2) over 120 min on day 1 and 8 every three weeks and 12 patients (aged > or =70 years) were treated with gemcitabine alone 1200 mg/m(2) over 120 min on day 1 and 8 every three weeks, for two courses. Simon's two stage minimax design was applied to calculate the sample size. Assuming p(0) (low conversion rate) 5%, p(1) (target conversion rate of interest) 20%, alpha error 0.05, beta error 0.10 a total of 29 evaluable patients had to be accrued during stage 1. In case at least one objective response was observed, a further nine evaluable patients had to be enrolled into the study during stage 2. The regimen was considered promising if > or =4 objective responses out of 38 evaluable patients were observed. RESULTS: Thirty-eight patients were evaluable for response and in five patients (with stable disease after two courses of gemcitabine 30' infusion) a partial response was observed (conversion rate 13.1%, 95% confidence interval 4.4-28%). Toxicities were more frequently observed with cisplatin plus 120-min gemcitabine infusion: grade 3-4 neutropenia, thrombocytopenia and anaemia in 28, 22 and 16% of the courses, respectively. CONCLUSIONS: The prolongation of gemcitabine infusion time is able to convert stable disease to partial response in 13% of the cases. The haematological toxicity seems enhanced with cisplatin plus gemcitabine prolonged infusion.
