Dose-intensification of MVAC with recombinant granulocyte colony-stimulating factor as initial therapy in advanced urothelial cancer Journal Article

Authors: Seidman, A. D.; Scher, H. I.; Gabrilove, J. L.; Bajorin, D. F.; Motzer, R. J.; O'Dell, M.; Curley, T.; Dershaw, D. D.; Quinlivan, S.; Tao, Y.; Fair, W. R.; Begg, C.; Bosl, G. J.
Article Title: Dose-intensification of MVAC with recombinant granulocyte colony-stimulating factor as initial therapy in advanced urothelial cancer
Abstract: Purpose: This study was undertaken to define an escalated dose schedule of methotrexate, vinblastine, doxorubicin, and cisplatin (E-MVAC) with hematopoietic growth-factor support, to define the ability to deliver E-MVAC with recombinant human granulocyte colony-stimulating factor (rhG-CSF) on 21 - and 14-day schedules, and to assess the ability of rhG-CSF to maintain dose-intensity over four cycles of chemotherapy. Patients and Methods: Twenty-three patients with transitional-cell carcinoma of the urothelium received E-MVAC in a phase I investigation. Patients were treated on an every-21-day (n = 19) or every-14-day schedule of administration (n = 4), with rhG-CSF support. Delivered dose-intensity was calculated at the completion of four cycles of therapy relative to the planned administration of conventional MVAC (relative dose-intensity [RDI]). Peripheral-blood progenitor cell kinetics in these patients were studied prospectively. Results: Overall, the delivered RDI was 33% higher than the previously reported delivered dose-intensity of MVAC without hematopoietic support (140% for doxorubicin, 51 % for cisplatin). Dose-intensity was well maintained through three cycles of therapy, after which leukopenia and thrombocytopenia became dose-limiting. Sixty-nine percent of patients with measurable disease responded, four (25%) with complete remissions. In five patients treated beyond the maximally tolerated dose (MTD), a 50- to 200-fold increase in G-CSF, granulocyte-macrophage CSF (GM-CSF), and interleukin-3 (IL-3)-responsive peripheral-blood progenitor cells over baseline was observed after 9 days of rhG-CSF administration. Conclusion: These findings demonstrate the feasibility and limitations of dose intensification of M-VAC with rhG-CSF. While the overall impact of the increased drug administration can only be assessed in randomized comparisons, the results of the present trial suggest that escalations of the components of the four-drug regimen are unlikely to improve significantly the outcome for patients with advanced urothelial tract tumors. © 1993 by American Society of Clinical Oncology.
Keywords: adolescent; adult; clinical article; treatment outcome; aged; neutropenia; cisplatin; doxorubicin; advanced cancer; cancer combination chemotherapy; methotrexate; leukopenia; thrombocytopenia; antineoplastic combined chemotherapy protocols; granulocyte macrophage colony stimulating factor; bone pain; deep vein thrombosis; vinblastine; stem cell; urologic neoplasms; cancer regression; recombinant proteins; urogenital tract tumor; phase 1 clinical trial; recombinant granulocyte colony stimulating factor; carcinoma, transitional cell; transitional cell carcinoma; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; artery thrombosis; middle age; dose time effect relation; maximum permissible dose; vasculitis; interleukin 3; subcutaneous drug administration; human; male; female; priority journal; article; support, u.s. gov't, p.h.s.
Journal Title: Journal of Clinical Oncology
Volume: 11
Issue: 3
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1993-03-01
Start Page: 408
End Page: 414
Language: English
DOI: 10.1200/jco.1993.11.3.408
PUBMED: 7680373
PROVIDER: scopus
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
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MSK Authors
  1. D David Dershaw
    177 Dershaw
  2. Dean Bajorin
    416 Bajorin
  3. Andrew D Seidman
    254 Seidman
  4. Colin B Begg
    239 Begg
  5. Robert Motzer
    769 Motzer
  6. Howard Scher
    835 Scher
  7. George Bosl
    270 Bosl
  8. William R Fair
    199 Fair