Phase I/II study of carboplatin and weekly paclitaxel for advanced non-small cell lung cancer

Abstract

7287 Background:This phase I/II study of carboplatin (C) and weekly paclitaxel (P) for advanced non-small cell lung cancer (NSCLC) aimed to determine maximum tolerated dose (MTD) and dose limiting toxicity (DLT) and to evaluate the efficacy and the feasibility of this regimen. Methods: Eligible patients (pts) had no prior chemotherapy, were 20–74 years old, PS 0–2, and had adequate organ functions. C was administered on day 1, while P was administered on days 1, 8, 15 on a schedule of 28 days. The initial dose was AUC=5 for C and 60mg/m2 for P. The dose for the second level was escalated by AUC=6 for C, while the dose of P was increased in increments of 10 mg/m2 up to 100 mg/m2(6 levels). DLT was defined as G4 neutropenia over 4 days, G3 febrile neutropenia, G4 thrombocytopenia, non-hematologic toxicity G3,depends on document reviewtreatment delay more than 3 weeks, or treatment refusal by pt during the study. MTD was defined when the incidence of DLT exceeds 33.3% at each dose level. Results:A total of 26 pts were enrolled and were evaluable for toxicity and response. The 26 pts received a total of 61 cycles of treatment. Patients characteristics were as follows: male/female: 24/2, median age: 59.2(37–72), PS 0–1/2: 25/1, Ad/Sq: 17/9, stage IIIA/IIIB/IV: 1/9/16. The MTD was estimated to be 100 mg/m2 since G3 infection as DLT occurred in 2 pts at level 6 (P 100 mg/m2). No DLT except for G3 infection was observed through the study, and neutropenia, neuropathy and myalgia were mild. G4 neutropenia occurred in only 7.9% of the 61 cycles. No G3 febrile neutropenia or G4 thrombocytopenia were observed. G1/G2 neuropathy occurred in only 6.3%/6% and G1/G2 myalgia occurred in only 4.8%/0%, respectively. The delivery rate of P was 98.4% for the total of 61 cycles (183 doses). All cycles were completed up to level 5. The response rate was 50.0% with PR in 13 pts. Conclusions: These results showed that the combination of C and weekly P is feasible and effective for advanced NSCLC. Especially, this combination schedule may reduce neutropenia, neuropathy and myalgia more markedly than the standard schedule of C and P. C AUC=6 and P 80–90mg/m2 should be recommended for a randomized study in order to confirm these promising findings. No significant financial relationships to disclose.