title: Phase II study of deoxyspergualin in metastatic breast cancer.
abstract: We conducted a phase II trial of the novel immunomodulatory/cytotoxic agent 15-deoxyspergualin in patients with metastatic breast cancer who had failed treatment with front-line chemotherapy. Thirty-eight courses of treatment were administered to fourteen patients enrolled in this trial, 25 at a dose of 1800 mg/m2/d (dose level 0) and 13 at a dose of 2150 mg/m2/d (dose level +1) administered by continuous intravenous infusion for 5 days. Treatment was well tolerated with neuromuscular side-effects (myalgias, paresthesias) and granulocytopenia (nadir granulocyte count of 0.50-0.99 x 10(9)/l) in two and three courses, respectively, as the only grade III toxicities. The neuromuscular toxicity of deoxyspergualin is probably related to the occurrence of hypomagnesemia. No partial or complete responses were observed in this study. One patient achieved a minor response but had progressive disease 65 weeks after enrollment. The response was observed coincident with an increase in T4/T8 ratio in the peripheral blood. The median time to progression for the entire cohort was eight weeks (range, 4-65 weeks). There was no clinical evidence of immunosuppression and no decrease in total peripheral blood lymphocyte counts or helper T-cells was observed. At the doses and schedule employed in this trial, deoxyspergualin does not appear to have significant activity against metastatic breast cancer resistant to front-line chemotherapy. The correlation between hypomagnesemia and neuromuscular toxicity of deoxyspergualin is an intriguing, previously unknown observation and requires further investigation.
authors.affiliation: Department of Breast and Gynecologic Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston.
authors.forename: K
authors.initials: K
authors.lastname: Dhingra
authors.forename: V
authors.initials: V
authors.lastname: Valero
authors.forename: L
authors.initials: L
authors.lastname: Gutierrez
authors.forename: R
authors.initials: R
authors.lastname: Theriault
authors.forename: D
authors.initials: D
authors.lastname: Booser
authors.forename: F
authors.initials: F
authors.lastname: Holmes
authors.forename: A
authors.initials: A
authors.lastname: Buzdar
authors.forename: G
authors.initials: G
authors.lastname: Fraschini
authors.forename: G
authors.initials: G
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D016516:CD4-CD8 Ratio; D005260:Female; D006146:Guanidines / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D008274:Magnesium / Q000097:blood; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009468:Neuromuscular Diseases / Q000139:chemically induced
chemical_list: D000903:Antibiotics, Antineoplastic; D006146:Guanidines; D008274:Magnesium; C037258:gusperimus