title: Phase I/II trial of gemcitabine plus cyclophosphamide in patients with metastatic breast carcinoma previously treated with taxanes.
abstract: The purpose of this study was to determine the maximum tolerated dose (MTD) of infusional gemcitabine given in conjunction with intravenous (i.v.) cyclophosphamide, and to determine whether the regimen produced a response rate of at least 40% in patients with metastatic breast cancer who have been previously treated with taxanes. Patients received cyclophosphamide (600 mg/m2) i.v. followed immediately by gemcitabine (100, 150, or 200 mg/m2) given as a 24-hour infusion (every 3 weeks) using an accelerated dose-escalation schema. Dose-limiting toxicity was defined as a neutrophil nadir < 500/microL, platelet nadir < 50,000/microL, or > or = grade 2 nonhematologic toxicity (> or = grade 3 toxicity during the standard dose-escalation portion of the study). Twelve patients received a total of 32 cycles of therapy. The MTD of gemcitabine was 150 mg/m2. Dose-limiting toxicities at 200 mg/m2 included neutropenia and mucositis. One patient with lymphangitic lung metastases had a partial response (8%; 95% confidence intervals: 0%, 23%). This patient developed grade 4 transaminase and total bilirubin elevation that occurred after the sixth cycle of therapy. The study was terminated due to an insufficient number of responses. The MTD of gemcitabine given as a 24-hour infusion is 150 mg/m2 when used in conjunction with cyclophosphamide (600 mg/m2) every 3 weeks. This regimen is not likely to produce more than a 40% response rate in patients with metastatic breast cancer previously treated with taxanes.
authors.affiliation: Department of Oncology, Albert Einstein Comprehensive Cancer Center, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Huda S
authors.initials: HS
authors.lastname: Salman
authors.forename: Katie
authors.initials: K
authors.lastname: Tanaka
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008875:Middle Aged; D016019:Survival Analysis; D043823:Taxoids; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D001952:Bridged-Ring Compounds; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D003520:Cyclophosphamide; D001219:Aspartate Aminotransferases; D001663:Bilirubin; D000093542:Gemcitabine