Escalated Therapy for Refractory Urothelial Tumors: Methotrexate- Vinblastine-Doxorubicin- Cisplatin Plus Unglycosylated Recombinant Human Granulocyte-macrophage Colony-Stimulating Factor

• Published in: JNCI : Journal of the National Cancer Institute 1990-04, Vol.82 (8), p.667-672
• Main Authors: Logothetis, Christopher J., Dexeus, Francisco H., Sella, Avishay, Amato, Robert J., Kilbourn, Robert G., Finn, Laury, Gutterman, Jordan U.
• Format: Article
• Language: English
• Subjects: Agranulocytosis - chemically induced; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone Marrow - drug effects; Cisplatin - administration & dosage; Colony-Stimulating Factors - administration & dosage; Colony-Stimulating Factors - therapeutic use; Doxorubicin - administration & dosage; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances - administration & dosage; Growth Substances - therapeutic use; Humans; Male; Medical sciences; Methotrexate - administration & dosage; Pharmacology. Drug treatments; Recombinant Proteins - administration & dosage; Recombinant Proteins - therapeutic use; Urinary Bladder Neoplasms - drug therapy; Vinblastine - administration & dosage
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/82.8.667

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[