Phase II studies of pemetrexed in metastatic breast and gynecologic cancers.
Pemetrexed (Alimta) is active in a variety of solid tumors, including breast and gynecologic cancers. Phase II trials of pemetrexed at a dose of 600 mg/m2 without vitamin B12 and folic acid supplementation in largely pretreated metastatic breast cancer patients demonstrated objective response rates of 21% and 28%, with generally manageable neutropenia constituting the primary toxicity. In phase II trials using 500 mg/m2 with or without vitamin supplementation in anthracycline- and taxane-pretreated patients, response rates were lower (approximately 9%) and treatment was generally well tolerated irrespective of vitamin supplementation status. A phase II trial is currently comparing pemetrexed doses of 600 and 900 mg/m2 with vitamin B12 supplementation in patients with previously untreated advanced breast cancer. In a phase II trial in patients with advanced cervical cancer, pemetrexed at 600 mg/m2 without vitamin supplementation and 500 mg/m2 with supplementation produced similar response rates, with the frequency of neutropenia being somewhat lower among patients receiving the lower dose and vitamin supplementation. Preliminary results in an ongoing phase II trial indicate activity of the regimen of gemcitabine (Gemzar) at 1,000 mg/m2 plus pemetrexed at 500 mg/m2 with vitamin supplementation in patients with ovarian cancer. Ongoing and future studies will establish optimal dosing regimens of pemetrexed and potential benefits of vitamin supplementation in the settings of metastatic breast cancer and gynecologic malignancies.
Smith
Ian
I
Medical Oncologist Royal Marsden Hospital, London, United Kingdom. ian.smith@rmh.nthames.nhs.uk
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D004334:Drug Administration Schedule; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage*; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000473:pathology; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006801:Humans; D000068437:Pemetrexed; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase