Phase II study of pemetrexed in patients pretreated with an anthracycline, a taxane, and capecitabine for advanced breast cancer.
BACKGROUND
This phase II study evaluated the efficacy, safety, and health outcomes of pemetrexed treatment in heavily pretreated patients with advanced breast cancer.


METHODS
Women with metastatic breast cancer, Karnofsky performance status > or = 70, and previous treatment with > or = 3 regimens containing anthracyclines, taxanes, and capecitabine were eligible. Pemetrexed 500 mg/m2 intravenous infusion was administered on day 1 of a 21-day treatment cycle.


RESULTS
Eighty patients were enrolled, and 60 received concurrent folic acid and vitamin B12 supplements per protocol amendment to minimize possible pemetrexed-related toxicity. The median numbers of cycles delivered were 3 for vitamin-supplemented patients and 2 for non-vitamin-supplemented patients. Regardless of vitamin supplementation, the overall response rate was 8% (95% CI, 3%-16.6%), stable disease was exhibited in 36% of patients, median time to disease progression was 2.9 months, and median survival was 8.2 months. Improvements in patient-reported symptoms ranged from 16.2% for pain intensity to 32.1% for nausea. Major grade 3/4 toxicities were hematologic, with grade 4 neutropenia in 10% of patients and grade 3 toxicities consisting primarily of neutropenia (29%) and leukopenia (21%). There were no clear trends of the effect of supplementation on toxicity.


CONCLUSIONS
Pemetrexed has modest antitumor activity and is well tolerated in heavily pretreated patients with breast cancer. Further evaluation of this multitargeted antifolate in advanced breast cancer is warranted.
O'Shaughnessy
Joyce A
JA
Texas Oncology, PA, USA. joyce.o'shaughnessy@usoncology.com
Clark
Romnee S
RS
Blum
Joanne L
JL
Mennel
Robert G
RG
Snyder
David
D
Ye
Zhishen
Z
Liepa
Astra M
AM
Melemed
Allen S
AS
Yardley
Denise A
DA
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D000068437:Pemetrexed; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
D018943:Anthracyclines; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000069287:Capecitabine; D005472:Fluorouracil