Paclitaxel by 1-h infusion in combination with carboplatin in advanced non-small cell lung carcinoma (NSCLC)

摘要: Abstract In our previous study, FCCC 93-024, paclitaxel by 24-h infusion combined with carboplatin yielded a response rate of 62% and median survival 54 weeks in advanced non-small cell lung cancer (NSCLC). Myelosuppression proved dose-limiting, requiring the routine use granulocyte-colony stimulating factor (G-CSF). Based on reported activity 1-h NSCLC minimal myelosuppression at doses 135 200 mg/m 2 every 3 suggestion dose–response relationship, we launched an intrapatient dose escalation trial combination paclitaxel. Chemotherapy-naive patients received 175 dosed to fixed targeted area under concentration–time curve (AUC) 7.5 three weekly intervals for six cycles. absence grade 4 myelosuppression, was escalated 35 /cycle basis maximum 280 cycle 4. G-CSF not routinely used. 57 (pts) were accrued from November 1994 through April 1996. 44 pts (77%) had Eastern Cooperative Oncology Group (ECOG) performance status 1. Median age 64 (range: 34–80) years. Cumulative peripheral sensory neuropathy dose-limiting prohibitive first 20 evaluable (cohort A): ⩾1 15 (75%), 6 (30%), generally occurring ⩾215 obligating have treatment halted disease progression. The protocol, therefore, revised initial reduced 40 215 , recapitulating original dosing schema used 93-024. enrolled this second cohort (B); 33 evaluable. Whilst 17 (52%) experienced neuropathy, neurotoxicity developed only (9%). also less pronounced, 42% exhibiting granulocytopenia 30% ⩾3 thrombocytopenia B compared 70% 50%, respectively A. Of 22 A, 12 (55%) major objective responses. 48.5 weeks, 1-year 45% 2-year 18%. B, 9 (27%) 46 47% 12%. Combination AUC is active NSCLC. Neurotoxicity, exceeding . Lower may be associated lower rates, but do appear compromise survival.