title: SWOG 8825: melphalan GM-CSF: a phase I study.
abstract: The use of intravenous melphalan at higher doses is limited by severe myelosuppression. It was postulated that GM-CSF would permit the use of higher dose melphalan with only moderate myelosuppression easily manageable in an outpatient setting. Therefore, a phase I study of intravenous melphalan utilizing GM-CSF (recombinant granulocyte-macrophage colony-stimulating factor) support was initiated. Intravenous melphalan at doses of 15-45 mg/m2 was administered every 28 days. GM-CSF was utilized at doses of 10-20 micrograms/kg/day subcutaneously Days 2-21 on a 28-day cycle. Twenty-five patients received 53 courses of therapy. The dose-limiting toxicities were severe or life-threatening granulocytopenia and thrombocytopenia. Utilizing 20 micrograms/kg/day GM-CSF, the maximum tolerated dose (MTD) of melphalan is 30 mg/m2 and, with 10 mg/kg/day GM-CSF, the maximum tolerated melphalan dose is only 20 mg/m2. One patient with ovarian cancer achieved a partial response. Because the reported MTD of intravenous melphalan without GM-CSF is 30 mg/m2, GM-CSF has not allowed sufficient escalation of the intravenous melphalan dose for routine outpatient use.
authors.affiliation: Wayne State University Medical Center, Detroit, Michigan 48201.
authors.forename: E
authors.initials: E
authors.lastname: Poplin
authors.forename: H
authors.initials: H
authors.lastname: Smith
authors.forename: B
authors.initials: B
authors.lastname: Behrens
authors.forename: B
authors.initials: B
authors.lastname: Redman
authors.forename: L
authors.initials: L
authors.lastname: Flaherty
authors.forename: J
authors.initials: J
authors.lastname: Neidhart
authors.forename: D
authors.initials: D
authors.lastname: Alberts
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000380:Agranulocytosis / Q000139:chemically induced / Q000517:prevention & control; D000740:Anemia / Q000139:chemically induced; D004341:Drug Evaluation; D016889:Endometrial Neoplasms / Q000188:drug therapy; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use / Q000633:toxicity*; D006801:Humans; D007890:Leiomyosarcoma / Q000188:drug therapy; D008558:Melphalan / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011994:Recombinant Proteins / Q000627:therapeutic use / Q000633:toxicity; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008558:Melphalan