title: Rebeccamycin analog for refractory breast cancer: a randomized phase II trial of dosing schedules.
abstract: Rebeccamycin analog (NSC 655649) is a synthetic antibiotic cytotoxic agent thought to inhibit topoisomerase function. We sought to determine the response rate to rebeccamycin analog among patients with refractory advanced breast cancer using two different treatment schedules. Eligible patients had measurable disease, central venous access, and one or two prior chemotherapy regimens for advanced cancer, or recurrence within 12 months of adjuvant chemotherapy. Patients were randomized to rebeccamycin analog on one of two treatment schedules: arm 1, 500 mg/m2 IV bolus every 21 days; arm 2, 140 mg/m2 IV bolus daily x 5 days, every 21 days. The primary study endpoint was response rate; a two stage accrual design evaluated each schedule separately. Forty-two women entered the trial, 21 on each arm. Prior chemotherapy regimens for metastatic breast cancer were: 0, n=4; 1, n=21; 2, n=17. Prior treatments (including adjuvant therapy) anthracyclines: 88%, taxanes 67%, 5FU-based therapy, 50%. There were 5 partial responses (overall response rate 12%), two in arm 1 and 3 in arm 2, all in patients with prior anthracycline-based adjuvant chemotherapy. Median time to progression was 2.1 months (range 1-14+ months). An additional 9 patients had stable disease as best response. Grade 3 or 4 toxicity rates were: anemia 5%, neutropenia 33%, thrombocytopenia 12%, RBC transfusion 14%, nausea/vomiting 10%. Toxicity profiles were similar between the treatment arms. Rebeccamycin analog is reasonably well tolerated on two different treatment schedules for advanced breast cancer, with modest clinical activity in this heavily pretreated population.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. hburstein@partners.org
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: Beth
authors.initials: B
authors.lastname: Overmoyer
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gelman
authors.forename: Paula
authors.initials: P
authors.lastname: Silverman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Savoie
authors.forename: Kathryn
authors.initials: K
authors.lastname: Clarke
authors.forename: Leda
authors.initials: L
authors.lastname: Dumadag
authors.forename: Jerry
authors.initials: J
authors.lastname: Younger
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D001943:Breast Neoplasms / Q000188:drug therapy*; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged
chemical_list: D000903:Antibiotics, Antineoplastic; D002227:Carbazoles; D007211:Indoles; C053339:rebeccamycin