Abstract
Purpose: To determine the maximally tolerated dose (MTD) of biweekly pemetrexed with gemcitabine plus B12 and folate supplementation in patients with advanced solid tumors and ovarian cancer.
Experimental Design: Patients with no prior pemetrexed or gemcitabine therapy enrolled in cohorts of three, expanding to six if dose-limiting toxicity (DLT) was observed. Pemetrexed, escalated from to 700 mg/m2, was given before gemcitabine 1,500 mg/m2 every 14 days. DLTs were grade 4 neutropenia lasting >7 days or febrile neutropenia, grade 4 or 3 thrombocytopenia (with bleeding), grade ≥3 nonhematologic toxicity, or treatment delay of ≥1 week due to unresolved toxicity.
Results: The ovarian cancer cohort enrolled 24 patients with unlimited prior cytotoxic chemotherapies. MTD was observed at pemetrexed 600 mg/m2, with 2 of 9 patients experiencing DLT. Most common grade 3 to 4 toxicities per patient were neutropenia (83%), leukopenia (67%), lymphopenia (73%), and febrile neutropenia (12%). Median cycle per patient was 8 (range, 1-16). Six of 21 (28%) patients had confirmed partial responses. Study protocol was modified for the solid tumor cohort (n = 30) to enroll patients with two or more prior cytotoxic regimens. MTD was observed at pemetrexed 500 mg/m2, with 1 of 9 patients experiencing DLT. Most common grade 3 to 4 toxicities per patient were neutropenia (63%), lymphopenia (43%), leukopenia (70%) and febrile neutropenia (6.6%). Median cycle per patient was 4 (range, 1-20). Three of 29 (10.3%) response-evaluable patients had confirmed partial responses: 2 squamous cell carcinomas of head and neck and 1 nasopharyngeal cancer.
Conclusion: MTDs for the solid tumor and ovarian cancer cohorts were reached at pemetrexed 500 and 600 mg/m2, respectively, given biweekly with gemcitabine 1,500 mg/m2.
- gemcitabine
- pemetrexed
- biweekly
- ovarian cancer
- solid tumor
Footnotes
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Grant support: Eli Lilly and Co., Lilly Oncology.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: Presented in part at the American Society of Clinical Oncology Annual Meeting; Atlanta, GA; 2006. Published in part in the Proceedings of the American Society of Clinical Oncology Annual Meeting; Chicago, IL; 2007.
- Accepted May 12, 2008.
- Received February 8, 2008.
- Revision received April 18, 2008.
Volume 14, Issue 19
