Phase I Study of Dose-Dense Alternating Doublets in Advanced Non—Small-Cell Lung Cancer

• Published in: Clinical lung cancer 2002-05, Vol.3 (4), p.265-270
• Main Authors: Vokes, Everett E., Charoentum, Chaiyut, Gordon, Gary S., Rudin, Charles M., Krauss, Stuart A., Hoffman, Philip C., Mauer, Ann M., Lee, Susie, Watson, Sylvia
• Format: Article
• Language: English
• Subjects: Alternating chemotherapy; Cisplatin; Docetaxel; Dose-dense chemotherapy; Gemcitabine; Vinorelbine
• ISSN: 1525-7304; 1938-0690
• DOI: 10.3816/CLC.2002.n.011

We performed a study to determine the feasibility of a rapidly alternating administration of cisplatin/vinorelbine (CV) and docetaxel/gemcitabine (DG) in the treatment of advanced non—small-cell lung cancer (NSCLC). Thirty-four patients with NSCLC (6% stage IIIB, 94% stage IV) were enrolled. The initial schema was to give CV on days 1 and 8 followed by DG on days 15 and 22, every 28 days. Granulocyte colony-stimulating factor (G-CSF) was used on days 9-14 and 23-28. Despite dose reductions, this sequence was not feasible. Therefore, the sequence was switched to give DG before CV, cycle duration was extended to 35 days, and G-CSF was given on days 2-7 and 23-28. Neutropenia and thrombocytopenia were dose-limiting toxicities. The recommended doses for phase II studies are docetaxel 75 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 60 mg/m2 on day 15, and vinorelbine 25 mg/m2 on days 15 and 22, every 35 days with G-CSF 5 μg/kg on days 2-7 and 23-28. However, treatment delays were required in subsequent cycles due to cumulative myelosuppression. A less intensive schedule is recommended for subsequent cycles for further testing. Overall response rate was 29% (95% confidence interval [CI], 14%–45%), and median survival for all patients was 11.8 months. One- and 2-year survival rates were 47% (95% CI, 30%–63%) and 14% (95% CI, 1.4%–40%), respectively. Although initial administration of this regimen was feasible, dose intensity could not be maintained in subsequent cycles due to cumulative myelosuppression. A sequential rather than alternating use of doublet regimens might be more readily feasible and may permit greater maintenance of dose intensity.