title: A randomized phase II non-comparative study of pemetrexed‑carboplatin and gemcitabine‑vinorelbine in anthracycline- and taxane-pretreated advanced breast cancer patients.
abstract: Pemetrexed-carboplatin and gemcitabine‑vinorelbine combination therapies were efficacious in phase II and phase III studies as first-line breast cancer treatment. Thus, Arm A and Arm B combinations were investigated in patients pretreated with anthracycline and taxanes. Women with advanced breast cancer, with ≥1 measurable lesion per RECIST, were stratified by line of treatment (1st, 2nd), visceral disease (yes/no), ECOG PS (0-1 vs. 2) and randomized 1:1 to Arm A (pemetrexed 600 mg/m², D1 i.v. q21; carboplatin, AUC 5, D1 i.v. q21) or Arm B (gemcitabine 1,200 mg/m² D1, D8 i.v. q21; vinorelbine 30 mg/m² D1, D8 i.v. q21). Treatment continued until progression. The primary endpoint was objective response rate (RR). Secondary endpoints were duration of response (DoR), time-to-response (TTR), time-to-progressive disease (TTPD), time-to-treatment failure (TTTF) and safety. A two-stage design was employed independently for each arm. Of 135 randomized patients, 125 (Arm A, n=64; Arm B, n=61) qualified for tumor-response analysis. The mean (standard deviation) number of cycles administered was 6.3 (4.13) in Arm A and 6.2 (4.39) in Arm B. Efficacy in Arm A and Arm B were: RR (95% CI), 26.6 (16.3-39.1) and 29.5 (18.5-42.6); time-to-events (months), DoR 7.7 and 7.5; TTPD, 5.1 and 5.6; TTR, 1.8 and 1.8; TTTF, 4.8 and 5.1; respectively. Most common grade 3/4 adverse events possibly related to study-drug were neutropenia, thrombocytopenia, anemia and leucopenia in Arm A and neutropenia, leucopenia and fatigue in Arm B. In this study, both combinations showed moderate activity as predefined RR was not reached and were well tolerated.
authors.affiliation: Romagnolo Scientific Institute for the Study and Treatment of Cancer, Meldola, Italy. direzione.scientifica@irst.emr.it
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.forename: Eva
authors.initials: E
authors.lastname: Carrasco
authors.forename: Siegfried
authors.initials: S
authors.lastname: Roesel
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Beatrice
authors.initials: B
authors.lastname: Uziely
authors.forename: Victoria
authors.initials: V
authors.lastname: Soldatenkova
authors.forename: Valerie
authors.initials: V
authors.lastname: Moreau
authors.forename: Durisala
authors.initials: D
authors.lastname: Desaiah
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauknecht
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; C080625:taxane; D014747:Vinblastine; D006147:Guanine; D016190:Carboplatin; D000077235:Vinorelbine; D000093542:Gemcitabine