title: A phase I trial of continuous-infusion cyclophosphamide in refractory cancer patients.
abstract: Cyclophosphamide demonstrates enhanced tumoricidal activity with decreased bone marrow toxicity when given on a divided-dose schedule in certain animal models. A total of 22 patients presenting with refractory metastatic cancer were treated in a phase I trial of continuous infusion of cyclophosphamide over 96 h. Granulocytopenia of less than 500/microliters that lasted for greater than 14 days or thrombocytopenia of less than 25,000/microliters that lasted for greater than 14 days was the target dose-limiting toxicity in the absence of nonhematologic grade 4 toxicity. The maximal tolerated dose was 7 g/m2. Three patients died. Of 21 evaluable patients, 9 responded, including 8/9 who had experienced disease progression during prior oxazaphosphorine-containing combination chemotherapy. Clinically meaningful responses were observed in patients who had demonstrated clinical resistance to an oxazaphosphorine drug given at lower doses.
authors.affiliation: Department of Medicine, Charles A. Dana Research Institute, Boston, MA.
authors.forename: J P
authors.initials: JP
authors.lastname: Eder
authors.forename: A D
authors.initials: AD
authors.lastname: Elias
authors.forename: L
authors.initials: L
authors.lastname: Ayash
authors.forename: C A
authors.initials: CA
authors.lastname: Wheeler
authors.forename: T C
authors.initials: TC
authors.lastname: Shea
authors.forename: L E
authors.initials: LE
authors.lastname: Schnipper
authors.forename: E
authors.initials: E
authors.lastname: Frei
authors.forename: K H
authors.initials: KH
authors.lastname: Antman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006801:Humans; D007262:Infusions, Intravenous; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D012074:Remission Induction; D013997:Time Factors
chemical_list: D003520:Cyclophosphamide; D015080:Mesna