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New Antifolate Shows Activity in Advanced Breast Cancer Patients

New Antifolate Shows Activity in Advanced Breast Cancer Patients

SAN FRANCISCO—As a salvage therapy in advanced breast cancer
patients who have failed prior therapy with anthracyclines or anthracenediones,
taxanes, and capecitabine (Xeloda), the investigational antifolate pemetrexed
disodium (Alimta) shows promising activity, according to clinical trial results
presented at the American Society of Clinical Oncology annual meeting (abstract

Currently, there are no data to guide oncologists in choosing chemotherapy
for metastatic breast cancer patients whose disease has progressed in spite of
treatment with the above-named agents, said Joyce O’Shaughnessy, MD,
co-director, breast cancer research, US Oncology, Dallas.

Pemetrexed disodium, Dr. O’Shaughnessy noted, is a cytotoxic compound
that inhibits three enzymes in folate-dependent pathways (pyrimidine and purine
biosynthesis). It has shown activity in non-small-cell lung cancer, breast,
pancreas, colorectal, and head and neck cancers in phase I/II studies, and, she
speculated, its activity may not be affected by mechanisms of capecitabine
resistance because of its several mechanisms of action.

In this study, metastatic breast cancer patients received pemetrexed
disodium (500 mg/m² as a 10-minute IV infusion) every 21 days with prophylactic
dexamethasone to prevent skin rash.

To date, 42 of 80 patients enrolled are evaluable for safety and efficacy.
The median age was 52 years (range, 33 to 75), and patients had a mean of four
prior chemotherapy regimens. Patients had metastases in soft tissue (48%), lung
(41%), liver (45%), and bone (30%).

Folic acid (350 to 600 µg orally) and vitamin B12 (1,000 µg IM) were
administered to 19 of 42 patients (45%) beginning after the 23rd patient. They
were added after it was observed that their administration substantially
reduced neutropenia and GI toxicity (see also article below). No dose
reductions or omissions were necessary in a total of 169 cycles administered
(median 2; range, 1 to 18).

Dr. O’Shaughnessy reported an objective response rate of 10%, with 5%
complete responses and 5% partial responses. Responses were
observed in skin, lymph nodes, and liver. Durations of the two complete
responses were 3.6 and 3.0 months and of the two partial responses, 3.2 and 2.8


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