A phase I trial of pemetrexed plus gemcitabine given biweekly with B-vitamin support in solid tumor malignancies or advanced epithelial ovarian cancer Journal Article
| Authors: | Hensley, M. L.; Larkin, J.; Fury, M.; Gerst, S.; Tai, D. F.; Sabbatini, P.; Konner, J.; Orlando, M.; Goss, T. L.; Aghajanian, C. A. |
| Article Title: | A phase I trial of pemetrexed plus gemcitabine given biweekly with B-vitamin support in solid tumor malignancies or advanced epithelial ovarian cancer |
| 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 1of 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. ©2008 American Association for Cancer Research. |
| Keywords: | adult; cancer chemotherapy; controlled study; treatment outcome; treatment response; aged; major clinical study; clinical trial; neutropenia; advanced cancer; drug efficacy; drug withdrawal; side effect; gemcitabine; antineoplastic agent; neoplasm; neoplasms; ovarian neoplasms; edema; antineoplastic metal complex; multiple cycle treatment; ovary cancer; cohort studies; anemia; bleeding; leukopenia; thrombocytopenia; antineoplastic combined chemotherapy protocols; dehydration; drug administration schedule; cohort analysis; herpes zoster; diet supplementation; alanine aminotransferase blood level; aspartate aminotransferase blood level; dizziness; drug dose escalation; febrile neutropenia; lymphocytopenia; rash; hyponatremia; head and neck cancer; guanine; ovary tumor; drug derivative; vitamin supplementation; dietary supplements; folic acid; maximum tolerated dose; phase 1 clinical trial; drug administration; nasopharynx cancer; deoxycytidine; glutamates; pemetrexed; ataxia; vitamin b complex; cyanocobalamin; glutamic acid derivative |
| Journal Title: | Clinical Cancer Research |
| Volume: | 14 |
| Issue: | 19 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2008-10-01 |
| Start Page: | 6310 |
| End Page: | 6316 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-08-0338 |
| PUBMED: | 18829514 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
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