TY - JOUR
T1 - A phase i trial of sorafenib plus gemcitabine and capecitabine for patients with advanced renal cell carcinoma
T2 - New York cancer consortium trial NCI 6981
AU - Tagawa, Scott T.
AU - Milowsky, Matthew I.
AU - Jeske, Stephanie
AU - Mazumdar, Madhu
AU - Kung, Sophia
AU - Sung, Max
AU - Lehrer, Deborah
AU - Matulich, Daniel
AU - Selzer, Jodi
AU - Wright, John J.
AU - Nanus, David M.
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - capecitabine
KW - chemotherapy
KW - gemcitabine
KW - renal cell carcinoma
KW - sorafenib
UR - http://www.scopus.com/inward/record.url?scp=80053344558&partnerID=8YFLogxK
U2 - 10.1097/COC.0b013e3181e9c0d7
DO - 10.1097/COC.0b013e3181e9c0d7
M3 - Article
C2 - 20881475
AN - SCOPUS:80053344558
SN - 0277-3732
VL - 34
SP - 443
EP - 448
JO - American Journal of Clinical Oncology: Cancer Clinical Trials
JF - American Journal of Clinical Oncology: Cancer Clinical Trials
IS - 5
ER -