PT  - JOURNAL ARTICLE
AU  - Hensley, Martee L.
AU  - Larkin, Joseph
AU  - Fury, Matthew
AU  - Gerst, Scott
AU  - Tai, D. Fritz
AU  - Sabbatini, Paul
AU  - Konner, Jason
AU  - Orlando, Mauro
AU  - Goss, Tiana L.
AU  - Aghajanian, Carol A.
TI  - A Phase I Trial of Pemetrexed Plus Gemcitabine Given Biweekly with B-Vitamin Support in Solid Tumor Malignancies or Advanced Epithelial Ovarian Cancer
AID  - 10.1158/1078-0432.CCR-08-0338
DP  - 2008 Oct 01
TA  - Clinical Cancer Research
PG  - 6310--6316
VI  - 14
IP  - 19
4099  - http://clincancerres.aacrjournals.org/content/14/19/6310.short
4100  - http://clincancerres.aacrjournals.org/content/14/19/6310.full
SO  - Clin Cancer Res2008 Oct 01; 14
AB  - 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.