Escalated therapy for refractory urothelial tumors: Methotrexate- vinblastine-doxorubicin- cisplatin plus unglycosylated recombinant human granulocyte-macrophage colony-stimulating factor

Christopher J. Logothetis, Francisco H. Dexeus, Avishay Sella, Robert J. Amato, Robert G. Kilbourn, Laury Finn, Jordan U. Gutterman

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103 Scopus citations

Abstract

Thirty-two assessable patients with metastatic urothelial tumors refractory to standard chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were treated with escalated doses of MVAC plus unglycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Results of this phase I trial revealed that escalated MVAC (30 mg of methotrexate/m2,4 mg of vinblastine/m2, 60 mg of doxorubicin/m2, and 100 mg of cisplatin/m2) can be tolerated by heavily pretreated patients. The side effects of rhGM-CSF are dose- and schedule-dependent. The maximum tolerated dose is 250 μg/m2 per day as a single dose administered subcutaneously (SC) for 10 consecutive days. This dose is well tolerated in outpatients, resulting in only modest fever and few side effects. The same dose delivered as a continuous infusion or a higher dose delivered either as a continuous infusion or SC caused significant side effects. For phase II trials, the starting dose of rhGM-CSF when combined with escalated MVAC is 120 μg/m2 per day SC for 10 consecutive days. Forty percent of the treated patients responded, seven (23%) with complete remission and five (17%) with partial remission. This response rate is higher than anticipated from such a modest dosage escalation in chemotherapy-refractory patients. ]J Natl Cancer Inst 82: 667-672,1990[

Original languageEnglish
Pages (from-to)667-672
Number of pages6
JournalJournal of the National Cancer Institute
Volume82
Issue number8
DOIs
StatePublished - 18 Apr 1990
Externally publishedYes

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