title: Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer.
abstract: 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 microg/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.
authors.affiliation: Department of Medicine, Section of Hematology and Oncology, University of Chicago Hospital and University of Chicago Cancer Research Center, Chicago, IL 60637-1470, USA. evokes@medicine.bsd.uchicago.edu
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Chaiyut
authors.initials: C
authors.lastname: Charoentum
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gordon
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Krauss
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hoffman
authors.forename: Ann M
authors.initials: AM
authors.lastname: Mauer
authors.forename: Susie
authors.initials: S
authors.lastname: Lee
authors.forename: Sylvia
authors.initials: S
authors.lastname: Watson