This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blayney, D. W. Articles by Johnson, D. H. Search for Related Content PubMed PubMed Citation Articles by Blayney, D. W. Articles by Johnson, D. H.

Increasing Chemotherapy Dose Density and Intensity: Phase I Trials in Non-Small Cell Lung Cancer and Non-Hodgkin’s Lymphoma

^a Wilshire Oncology Medical Group, Inc., Pasadena, California, USA; ^b Department of Medical Affairs, Amgen Inc., Thousand Oaks, California, USA; ^c Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA

Correspondence: Douglas W. Blayney, M.D., University of Michigan Comprehensive Cancer Center, C365 Med Inn Building, Ann Arbor, Michigan 48109-0848, USA. Telephone: 734-615-7228; Fax: 734-615-2109; e-mail: dblayney{at}med.umich.edu

Dose densification and dose escalation of cytotoxic chemotherapy may be important in improving the cure rates of chemotherapy-responsive cancers. We conducted two phase I studies, in non-small cell lung cancer (NSCLC) and in lymphoma, to explore the possibility of intensifying chemotherapy by compressing the delivery of and escalating the dose of standard combination chemotherapy. One study used etoposide and cisplatin chemotherapy in patients with unresectable stage III or IV NSCLC, intensifying chemotherapy by reducing the cycle length. The second study used cyclophosphamide, doxorubicin, vincristine, and prednisone, CHOP chemotherapy, in the treatment of stage II–IV intermediate or immunoblastic high-grade lymphoma, intensifying chemotherapy first by reducing the cycle length and then by escalating the dosages of cyclophosphamide and doxorubicin. Filgrastim support was used during dose intensification. Fifty-five patients with NSCLC and 49 with non-Hodgkin’s lymphoma (NHL) were enrolled and treated in successive cohorts. At standard dosages and intervals of chemotherapy, filgrastim support resulted in incidences of grade 3 and 4 neutropenia that were between 62% and 77% lower than those in the no-filgrastim control; the mean duration of neutropenia was, likewise, more than 80% lower. Absolute neutrophil counts were 2 x 10⁹/l at day 14 in virtually 100% of patients receiving filgrastim. In the NSCLC trial, etoposide and cisplatin were intensified by >50%, and in the lymphoma trial, cyclophosphamide was intensified by 270% and doxorubicin was intensified by 87%. Chemotherapy reductions or delays for neutropenia were rare in the groups receiving filgrastim; but at higher chemotherapy intensities, dose-limiting thrombocytopenia was encountered. We conclude that the delivery of myelosuppressive chemotherapy in both a dose-intense and a dose-dense manner is feasible with filgrastim support.

Key Words. Chemotherapy • Neutropenia • Non-small cell lung carcinoma • Non-Hodgkin’s lymphoma • Drug dose-response relationships • Filgrastim

This article has been cited by other articles:

				P. G. Gobbi, C. Broglia, F. Valentino, C. Mammi, M. Lombardo, F. Merli, S. Luminari, G. Polimeno, A. Riezzo, P. Lambelet, et al. The role of dose size in a chemotherapy regimen (ProMECE-CytaBOM) for the first-line treatment of large B-cell lymphomas: a randomized trial by the Gruppo Italiano Studio Linfomi (GISL) Ann. Onc., April 1, 2006; 17(4): 676 - 682. [Abstract] [Full Text] [PDF]