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Activity of multitargeted antifolate (pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma
Author(s) -
John William,
Picus Joel,
Blanke Charles D.,
Clark Jeffery W.,
Schulman Lawrence N.,
Rowinsky Eric K.,
Thornton Donald E.,
Loehrer Patrick J.
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(20000415)88:8<1807::aid-cncr8>3.0.co;2-l
Subject(s) - medicine , neutropenia , gastroenterology , anemia , antifolate , pemetrexed , toxicity , vitamin d and neurology , surgery , chemotherapy , antimetabolite , cisplatin
BACKGROUND The aim of this study was to confirm the activity and assess the safety profile of multitargeted antifolate (MTA) for patients with metastatic colorectal adenocarcinoma. METHODS Forty‐six patients were enrolled in the study, 35 with colon and 11 with rectal carcinoma. Adjuvant therapy was allowed if completed 1 year previously. Patients received MTA 600 mg/m 2 as a 10‐minute intravenous infusion once every 21 days. Blood samples were taken every cycle for pharmacokinetic and vitamin metabolite assays. RESULTS Among 39 patients eligible for efficacy analysis, 1 complete response and 5 partial responses were identified, for an overall response rate of 15.4% (95% confidence interval [CI], 4.1–26.7%) for all patients. Fifteen patients had stable disease, with 9 living longer than 1 year. The median survival was 16.2 months (95% CI, 10.5–17.0%); 65% of patients were alive at 1 year, and the median time to progression was 4.4 months (range, 3.2–5.7 months). The main toxicities were hematologic, with common toxicity criteria (CTC) Grades 3 or 4 noted as follows: thrombocytopenia (18%), neutropenia (55%), and anemia (18%). Nonhematologic toxicities included Grade 2 or 3 skin reaction (53%), ameliorated by dexamethasone, and Grade 3 transaminases (23%). Dose omissions were not required and 21% of doses were reduced. CONCLUSIONS MTA has clear activity in patients with colorectal carcinoma, and encouraging survival times were noted. MTA was well tolerated in this patient group, but myelosuppression was frequent. Toxicity may be increased with folate deficiency. Cancer 2000;88:1807–13. © 2000 American Cancer Society.