title: Results of a phase II study of pemetrexed as first-line chemotherapy in patients with advanced or metastatic breast cancer.
abstract: Palliation is the primary goal in metastatic breast cancer (MBC), and safe, efficacious, new single-agent options are needed. Pemetrexed, an antifolate, inhibits several folate-dependent enzymes involved in purine biosynthesis. The primary goal of this study was to determine the objective response rate in patients with advanced or MBC given pemetrexed as a first-line, dose-dense, every 2-week chemotherapy. Women with HER2-negative advanced or MBC, without prior cytotoxic treatment for this stage of disease, were treated with intravenous pemetrexed 600 mg/m² on Day 1 of each 14-day cycle. Standard dexamethasone, folic acid, and vitamin B(12) premedications were given. 37 patients enrolled; 36 received ≥ 1 dose of pemetrexed and 35 were evaluable for response. Median age of patients was 61.4 years, 76% were hormone receptor positive (ER+ and/or PR+). Prior treatment included adjuvant chemotherapy (57%) and/or endocrine (65%). Patients received a median of 6 cycles of pemetrexed (range, 1-21). Based on 35 evaluable patients, the overall response rate (ORR) was 26% (1 CR and 8 PR), and the clinical benefit rate (CR+ PR+ stable disease [SD] ≥ 6 months) was 40%. Median progression-free survival (PFS) was 4.1 months (range, <1-22.4). Median overall survival (OS) was 18.9 months (range, <1-27.7). Grades 3-4 treatment-related toxicities included: neutropenia (36%), leukopenia (17%), fatigue (14%), and anemia (14%). Grade 1/2 alopecia was seen in 8% of patients. This phase II study of dose-dense, single-agent pemetrexed showed moderate activity in the first-line setting with acceptable toxicity and no significant alopecia.
authors.affiliation: US Oncology Research, Inc., The Woodlands, TX, USA, Nicholas.Robert@usoncology.com
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Robert
authors.forename: Paul R
authors.initials: PR
authors.lastname: Conkling
authors.forename: Mark A
authors.initials: MA
authors.lastname: O'Rourke
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kuefler
authors.forename: Kristi J
authors.initials: KJ
authors.lastname: McIntyre
authors.forename: Feng
authors.initials: F
authors.lastname: Zhan
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Oluwatoyin O
authors.initials: OO
authors.lastname: Shonukan
authors.forename: Joyce A
authors.initials: JA
authors.lastname: O'Shaughnessy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D000068437:Pemetrexed; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000556:secondary; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D006147:Guanine; D000068437:Pemetrexed; D018719:Erb-b2 Receptor Tyrosine Kinases