TY - JOUR
T1 - A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver
AU - Tsimberidou, Apostolia M.
AU - Fu, Siqing
AU - Ng, Chaan
AU - Lim, Jo Ann
AU - Wen, Sijin
AU - Hong, David
AU - Wheler, Jennifer
AU - Bedikian, Agop Y.
AU - Eng, Cathy
AU - Wallace, Michael
AU - Camacho, Luis H.
AU - Kurzrock, Razelle
PY - 2010/9/1
Y1 - 2010/9/1
N2 - BACKGROUND: Liver metastases in patients with cancer are associated with poor survival. The authors of this report conducted a phase 1 study of hepatic arterial infusion (HAI) oxaliplatin combination therapy in patients with advanced cancer and liver metastases. METHODS: Treatment consisted of escalating doses of HAI oxaliplatin 60 mg/m2 to 175 mg/m2 and intra-arterial heparin 3000 IU (Day 1); leucovorin 200 mg/m2 intravenously (iv) and 5-fluorouracil 300 mg/m2 bolus plus 600 mg/m2 iv (Days 1 and 2); and bevacizumab 10 mg/kg iv (Day 3). A conventional "3 + 3" design was used. RESULTS: Fifty-seven patients were treated, including 30 women and 27 men. The median age was 57 years, and the patients had received a median of 3 prior therapies (range, 1-7 prior therapies). The most common cancer was colorectal (n = 29). Overall, 204 cycles were administered (median per patient, 2 cycles; range, 1-17 cycles). The maximum tolerated dose (MTD) of HAI oxaliplatin was 140 mg/m2. Dose-limiting toxicities were grade 4 thrombocytopenia (n = 1) and grade 4 hypokalemia (n = 1) at 150 mg/m2 (n = 5). Thirty-three patients (58%) had no toxicity greater than grade 1. The most common toxicities were thrombocytopenia (n = 19), fatigue (n = 15), nausea/vomiting (n = 6), constipation (n = 6), and diarrhea (n = 4). Of 55 patients who were evaluable for response (according to Response Evaluation Criteria in Solid Tumors), 4 patients (7%) had a partial response (PR), and 32 patients (58%) had stable disease (SD), including 15 patients (48%) who had SD for ≥4 months. Of 28 patients with colorectal cancer, 3 patients (11%) had a PR, and 9 patients (32%) had SD for ≥4 months. CONCLUSIONS: HAI oxaliplatin combined with systemic 5-fluorouracil, leucovorin, and bevacizumab had antitumor activity in patients with advanced cancer and liver metastases, and the current results indicated that this combination warrants further study.
AB - BACKGROUND: Liver metastases in patients with cancer are associated with poor survival. The authors of this report conducted a phase 1 study of hepatic arterial infusion (HAI) oxaliplatin combination therapy in patients with advanced cancer and liver metastases. METHODS: Treatment consisted of escalating doses of HAI oxaliplatin 60 mg/m2 to 175 mg/m2 and intra-arterial heparin 3000 IU (Day 1); leucovorin 200 mg/m2 intravenously (iv) and 5-fluorouracil 300 mg/m2 bolus plus 600 mg/m2 iv (Days 1 and 2); and bevacizumab 10 mg/kg iv (Day 3). A conventional "3 + 3" design was used. RESULTS: Fifty-seven patients were treated, including 30 women and 27 men. The median age was 57 years, and the patients had received a median of 3 prior therapies (range, 1-7 prior therapies). The most common cancer was colorectal (n = 29). Overall, 204 cycles were administered (median per patient, 2 cycles; range, 1-17 cycles). The maximum tolerated dose (MTD) of HAI oxaliplatin was 140 mg/m2. Dose-limiting toxicities were grade 4 thrombocytopenia (n = 1) and grade 4 hypokalemia (n = 1) at 150 mg/m2 (n = 5). Thirty-three patients (58%) had no toxicity greater than grade 1. The most common toxicities were thrombocytopenia (n = 19), fatigue (n = 15), nausea/vomiting (n = 6), constipation (n = 6), and diarrhea (n = 4). Of 55 patients who were evaluable for response (according to Response Evaluation Criteria in Solid Tumors), 4 patients (7%) had a partial response (PR), and 32 patients (58%) had stable disease (SD), including 15 patients (48%) who had SD for ≥4 months. Of 28 patients with colorectal cancer, 3 patients (11%) had a PR, and 9 patients (32%) had SD for ≥4 months. CONCLUSIONS: HAI oxaliplatin combined with systemic 5-fluorouracil, leucovorin, and bevacizumab had antitumor activity in patients with advanced cancer and liver metastases, and the current results indicated that this combination warrants further study.
KW - Fluorouracil
KW - Hepatic arterial infusion
KW - Liver
KW - Oxaliplatin
KW - Solid tumors
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U2 - 10.1002/cncr.25277
DO - 10.1002/cncr.25277
M3 - Article
C2 - 20564148
AN - SCOPUS:77956791334
SN - 0008-543X
VL - 116
SP - 4086
EP - 4094
JO - Cancer
JF - Cancer
IS - 17
ER -