title: Escalated therapy for refractory urothelial tumors: methotrexate-vinblastine-doxorubicin-cisplatin plus unglycosylated recombinant human granulocyte-macrophage colony-stimulating factor.
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 micrograms/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 micrograms/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.
authors.affiliation: Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
authors.forename: C J
authors.initials: CJ
authors.lastname: Logothetis
authors.forename: F H
authors.initials: FH
authors.lastname: Dexeus
authors.forename: A
authors.initials: A
authors.lastname: Sella
authors.forename: R J
authors.initials: RJ
authors.lastname: Amato
authors.forename: R G
authors.initials: RG
authors.lastname: Kilbourn
authors.forename: L
authors.initials: L
authors.lastname: Finn
authors.forename: J U
authors.initials: JU
authors.lastname: Gutterman
mesh_terms: D000380:Agranulocytosis / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D003115:Colony-Stimulating Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D014747:Vinblastine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin; D008727:Methotrexate