title: A randomized, prospective, comparative, multicentre trial of a single combination versus alternating combinations of antitumour drugs in advanced breast cancer.
abstract: A prospective, multicentre trial was conducted in 262 patients with advanced breast cancer randomized to receive every 3 weeks either: (i) a single five-drug combination of adriamycin (50 mg), vincristine (1.5 mg) and 5-fluorouracil (750 mg) given intravenously; with methotrexate (50 mg) intramuscularly and chlorambucil (10 mg) orally all at time zero, followed by three further doses of chlorambucil (10 mg) at 6-h intervals, or (ii) one course of two alternating three-drug combinations consisting of regimen A--vincristine (1.5 mg), adriamycin (70 mg) and methotrexate (50 mg) and regimen B--5-fluorouracil (750 mg) and vindesine (5 mg) intravenously with cyclophosphamide (50 mg) orally at time zero, followed by three further doses of cyclophosphamide (50 mg) at 6-h intervals. Results show that overall response rates to chemotherapy were comparable in the two arms of this study being 63% (83 of 131 patients) for the single combination and 64% (84 of 131 patients) for the alternating combinations. Response rates according to menopausal status indicate no significant difference for the two arms of this study. However overall, combining all patients treated with either the single or the alternating combinations, post-menopausal patients had a significantly lower response rate (57%) compared with pre-menopausal patients (76%), P less than 0.05. Overall serious side-effects were minimal and were similar in both treatment groups. Response durations and overall survival data, which are essentially similar for the two treatment groups, proved disappointing with a median response duration of only approx. 6 months and overall median survival only slightly in excess of 1 year. Alternative treatment approaches are needed to maintain the remissions initially achieved in metastatic breast cancer.
authors.forename: M F
authors.initials: MF
authors.lastname: Spittle
authors.forename: B T
authors.initials: BT
authors.lastname: Hill
authors.forename: M J
authors.initials: MJ
authors.lastname: Ostrowski
authors.forename: K D
authors.initials: KD
authors.lastname: Macrae
authors.forename: T D
authors.initials: TD
authors.lastname: Bates
authors.forename: W M
authors.initials: WM
authors.lastname: Martin
authors.forename: N T
authors.initials: NT
authors.lastname: Nicol
authors.forename: G A
authors.initials: GA
authors.lastname: Edelstyn
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002699:Chlorambucil / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D011897:Random Allocation; D014750:Vincristine / Q000008:administration & dosage; D014751:Vindesine / Q000008:administration & dosage
chemical_list: D002699:Chlorambucil; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D014751:Vindesine; D005472:Fluorouracil; D008727:Methotrexate