A phase i trial of sorafenib plus gemcitabine and capecitabine for patients with advanced renal cell carcinoma: New York cancer consortium trial NCI 6981 Journal Article

Authors: Tagawa, S. T.; Milowsky, M. I.; Jeske, S.; Mazumdar, M.; Kung, S.; Sung, M.; Lehrer, D.; Matulich, D.; Selzer, J.; Wright, J. J.; Nanus, D. M.
Article Title: A phase i trial of sorafenib plus gemcitabine and capecitabine for patients with advanced renal cell carcinoma: New York cancer consortium trial NCI 6981
Abstract: OBJECTIVE: To define the safety [dose limiting toxicity (DLT)] and recommended phase II dose of the combination of sorafenib plus gemcitabine and capecitabine for advanced renal cell carcinoma (RCC). METHODS: In this phase I dose-escalation study, cohorts of 3 to 6 patients with metastatic RCC received sorafenib (200 or 400 mg po BID), gemcitabine (750 or 1000 mg/m intravenous on days 1 and 8), and capecitabine (415 or 622 mg/m po BID days 1-14) every 21 days using a standard 3+3 design. RESULTS: Fifteen patients with advanced RCC (93% with clear cell histology and 87% treatment naive) received treatment. The recommended phase II doses for the combination were sorafenib 200 mg/m BID continuously plus gemcitabine 750 mg/m intravenous days 1 and 8 and capecitabine 415 mg/m BID days 1 to 14, every 21 days. Of the 15 patients, 3 developed dose-limiting hand-foot syndrome during the first 2 cycles; 2 additional DLTs were grade 3 mucositis and transaminase elevation. Four of 14 evaluable patients had a partial response by response evaluation criteria in solid tumors (29%; 95% confidence interval (CI): 8, 58%). Median progression-free survival was 7.5 months (95% CI-0, 18.7), and median overall survival has not been reached at a median follow-up of 28.8 months. The median number of treatment cycles given was 7 (range, 2-38+). CONCLUSIONS: The combination of sorafenib plus gemcitabine and capecitabine is tolerable, but requires attenuation of sorafenib and capecitabine dosing because of the overlapping toxicity of hand-foot syndrome. Antitumor activity was observed leading to an ongoing phase II trial. Copyright © 2011 by Lippincott Williams & Wilkins.
Keywords: adult; cancer survival; clinical article; treatment outcome; treatment response; aged; bone neoplasms; middle aged; survival rate; overall survival; drug tolerability; fatigue; neutropenia; sorafenib; fluorouracil; advanced cancer; cancer combination chemotherapy; dose response; drug dose reduction; drug safety; drug withdrawal; recommended drug dose; side effect; benzenesulfonates; liver neoplasms; pyridines; bone metastasis; capecitabine; gemcitabine; chemotherapy; follow up; follow-up studies; lymph node metastasis; lymphatic metastasis; progression free survival; multiple cycle treatment; anemia; mucosa inflammation; thrombocytopenia; antineoplastic combined chemotherapy protocols; lung neoplasms; deep vein thrombosis; antineoplastic activity; renal cell carcinoma; kidney carcinoma; kidney neoplasms; abdominal pain; drug dose escalation; febrile neutropenia; pneumonia; alanine aminotransferase; hypoalbuminemia; liver metastasis; lung metastasis; carcinoma, renal cell; patient compliance; visceral metastasis; maximum tolerated dose; phase 1 clinical trial; clear cell carcinoma; hand foot syndrome; deoxycytidine; proteinuria; dose limiting toxicity; catheter thrombosis; kidney sarcoma
Journal Title: American Journal of Clinical Oncology
Volume: 34
Issue: 5
ISSN: 0277-3732
Publisher: Lippincott Williams & Wilkins  
Date Published: 2011-10-01
Start Page: 443
End Page: 448
Language: English
DOI: 10.1097/COC.0b013e3181e9c0d7
PROVIDER: scopus
PUBMED: 20881475
Notes: --- - "Export Date: 2 November 2011" - "CODEN: AJCOD" - "Source: Scopus"
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