title: AIDS Clinical Trials Group Study 094: a phase I/II trial of ABV chemotherapy with zidovudine and recombinant human GM-CSF in AIDS-related Kaposi's sarcoma.
abstract: OBJECTIVE
  To define the maximum tolerated dose of doxorubicin when combined with fixed doses of bleomycin, vincristine, zidovudine, and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) in patients with advanced AIDS-related Kaposi's sarcoma.
  
  
  METHODS
  Twenty male patients were treated with zidovudine at doses of either 100 or 200 mg by mouth every 4 hours, and cytotoxic chemotherapy with bleomycin 10 U/m2 and vincristine 1.4 mg/m2 by vein every 2 weeks. Four successive cohorts received fixed doses of doxorubicin given intravenously every 2 weeks: two cohorts each received 10 mg/m2 (levels 1, 2) or 20 mg/m2 (levels 3, 4). The first cohort received rhGM-CSF at a dose of 10 micrograms/ kg, given subcutaneously on days 2 through 11 (level 1). Due to toxicity, the dose of rhGM-CSF was reduced to 5 micrograms/kg (levels 2, 3) and then to 2.5 micrograms/kg (level 4).
  
  
  RESULTS
  The dose-limiting toxicity was severe neutropenia, occurring in 10 patients. Severe neutropenic episodes occurred after a median of three cycles of chemotherapy, with the nadir occurring after 14 days (median). Moderate neutropenia occurred in 14% of all cycles administered. Constitutional toxicities of moderate or greater severity occurred in four patients. Five of 10 patients at a doxorubicin dose of 20 mg/m2 (levels 3 and 4) experienced severe neutropenia. Thus, doxorubicin at 10 mg/m2, with BV (bleomycin, vincristine chemotherapy), zidovudine (100 mg five times daily), and rhGM-CSF (5 micrograms/kg/day), was defined as the maximum tolerated dose.
  
  
  CONCLUSIONS
  The maximum tolerated dose of doxorubicin is 10 mg/ m2 every 2 weeks when given in combination with BV chemotherapy, zidovudine, and rhGM-CSF. While the addition of rhGM-CSF at doses of 2.5 to 5 micrograms/kg decreased the duration of neutropenia, it did not prevent the occurrence of severe neutropenia from combined myelotoxic therapy.
authors.affiliation: Department of Internal Medicine, University of Southern California School of Medicine, Los Angeles, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Gill
authors.forename: R T
authors.initials: RT
authors.lastname: Mitsuyasu
authors.forename: T
authors.initials: T
authors.lastname: Montgomery
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: S
authors.initials: S
authors.lastname: Cabriales
authors.forename: M
authors.initials: M
authors.lastname: Testa
authors.forename: B M
authors.initials: BM
authors.lastname: Espina
authors.forename: A M
authors.initials: AM
authors.lastname: Levine
authors.forename: S A
authors.initials: SA
authors.lastname: Miles
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008168:Lung / Q000187:drug effects; D008297:Male; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D001761:Bleomycin; D015215:Zidovudine; D014750:Vincristine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor