Search

Purpose To estimate the safety, activity, and impact on quality of life of a combination of gemcitabine and pemetrexed in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in the context of a randomized two-stage phase II study. Patients and methods Patients in stage IIIB or IV NSCLC were randomly allocated to receive either gemcitabine 1250mg/m 2 on day 1, and pemetrexed (Alimta) 500mg/m 2 followed by gemcitabine 1250mg/m 2 on day 8 of a 3-weekly cycle (GA arm), or paclitaxel 120mg/m 2 followed by gemcitabine 1000mg/m 2 , both given on days 1 and 8 of a 3-weekly cycle (PG arm). Results 105 (GA arm, 51; PG arm, 54) eligible patients (stage IV, 32 and 30, respectively) were enrolled into this study; thereafter, accrual was stopped due to first-stage analysis. The response rate was 20% (95% confidence interval [CI], 10–33%) in the GA arm, and 32% (95% CI, 20–46%) in the PG arm. Median progression-free survival was 5.1 (95% CI, 3.7–6.5) months in the GA arm, and 8.3 (95% CI, 5.9–10.7) months in the PG arm, while median overall survival was 10.5 (95% CI 7.1–13.9), and 13.3 (95% CI 11.7–14.9) months, respectively. Severe neutropenia (36% vs 22%), and febrile neutropenia (14% vs 7%) were more common with the GA regimen, while hair loss (52% vs 16%) and any grade peripheral neuropathy (31% vs 2%) occurred more frequently with PG regimen. Other severe side effects of GA regimen were diarrhoea (10%), liver enzyme derangement (10%), and fatigue (8%). Conclusion The GA regimen was tolerated and moderately active in advanced or metastatic NSCLC. However, this combination did not yield any advantage in comparison with the PG regimen, and does not deserve further evaluation.

Summary Purpose This study was undertaken to select the best schedule of administration for the paclitaxel plus gemcitabine combination in fit elderly patients affected by locally advanced or metastatic non-small cell lung cancer (NSCLC). Patients and methods Ninety-eight patients in stage III or IV NSCLC, aged 70 years or more and in ECOG performance status (PS) ≤ 1, were randomly allocated to receive: paclitaxel 80 mg/m 2 plus gemcitabine 1000 mg/m 2 i.v. on days 1 and 8, with an intra-patient alternated dose escalation up to 100 and 1200 mg/m 2 , respectively, over three cycles (arm A); or paclitaxel 80 mg/m 2 followed by gemcitabine 1000 mg/m 2 i.v. (100 min) on days 1 and 8 (arm B). Treatment was repeated in both arms every 3 weeks for a maximum of six cycles. Results With a median of 3 (range, 1–6) delivered cycles, the two schedules yielded a similar response rate (25% versus 26%), failure-free survival (median, 3.3 months versus 3.2 months), progression-free survival (median, 5.1 months versus 5.2 months), and overall survival (median, 9.7 months versus 9.6 months). Survival was independently affected by the PS of patients and by the metastatic spread. Severe side effects were comparable and negligible in both arms. Conclusion A substantial difference between these two schedules in terms of efficacy and safety can be ruled-out. Paclitaxel plus gemcitabine is an advisable combination for treating fit elderly patients with advanced NSCLC.