title: Escalated M-VAC chemotherapy and recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) in patients with advanced urothelial tract tumors.
abstract: BACKGROUND
  The M-VAC regimen (methotrexate, vinblastine, adriamycin, and cisplatin) has significant antitumor activity in patients with advanced urothelial tract cancer. Growth factors may provide the possibility of treating patients with higher doses of chemotherapy, for longer periods, with less morbidity, and improved results. A trial of an escalated dosage of M-VAC with recombinant GM-CSF (rhGM-CSF) was initiated.
  
  
  METHODS
  23 patients were treated with an escalated dose of M-VAC every 2 weeks plus rhGM-CSF 250 micrograms/m2 s.c. days 4-10. Dose level I (n = 13) was 1.65 times the dose of standard M-VAC. Adriamycin and cisplatin were given at 2.5 times the dose of standard M-VAC. Dose level II (n = 10) was a relative dose intensity of 1.95. Adriamycin and cisplatin were both given at 2.9 times the dose.
  
  
  CONCLUSIONS
  The response rate was 70% (95% CI 60%-80%). Seven patients (30%) had CR, and 9 (39%) had a PR. Five (22%) patients had stable disease and 2 (9%) had progression. Of the CR patients, 3 had the CR confirmed pathologically (CRp). Response occurred in 11 patients treated at dose level I and 5 at dose level II. Toxicity was primarily hematologic. Dose level II was too toxic due to thrombocytopenia. Non-hematologic toxicity was minimal. The value of this schedule (dose level I) compared to standard M-VAC will be further evaluated in a randomized trial to be initiated by the Genitourinary Group of the EORTC.
authors.affiliation: Regina Elena Cancer Institute, Rome, Italy.
authors.forename: C N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: P H
authors.initials: PH
authors.lastname: de Mulder
authors.forename: A T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: S D
authors.initials: SD
authors.lastname: Fossa
authors.forename: D
authors.initials: D
authors.lastname: Giannarelli
authors.forename: J R
authors.initials: JR
authors.lastname: Soedirman
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D014565:Urogenital Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011994:Recombinant Proteins; D014747:Vinblastine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin; D008727:Methotrexate