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.

Phase I study of pemetrexed with sorafenib in advanced solid tumors

“…It has also demonstrated modest activity in previously untreated breast cancer [1]. Pemetrexed has been shown to have more than one mechanism of action in tumor cells as illustrated by the continued anti-proliferative effect of the drug in cells exposed to exogenous thymidine (which prevents the cytotoxic effects of thymidylate synthase inhibition) [2–5].…”

Eribulin (Halaven): a new, effective treatment for women with heavily pretreated metastatic breast cancer

“…Initially used principally in the metastatic setting, the former two are increasingly part of adjuvant regimens. ixabepilone, 10 vinorelbine, 11 gemcitabine, 12 pemetrexed, 13 and the platinums. 14 In addition, the value of retreatment with an agent to which the patient has previously been exposed remains unclear.…”

A Systemic Analysis on Pemetrexed in Treating Patients with Breast Cancer

“…Via steps of screening the title and reading the abstract, 10 studies were identified (Amadori D 2013;Dittrich C 2012;Robert NJ 2011;Martin M.2009 When pemetrexed was used in second line chemotherapy, 5 studies included in this study are presented and the short-term outcomes suggested that the response rate of Deng et al (2013) (2001) was 26%. Totally, 513 patients were enrolled and 167 patients achieved CR or PR, the pooled response rate thus was 39/281 (13.9%).…”

“…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 (Robert et al, 2011).…”