@article{oai:soar-ir.repo.nii.ac.jp:00020228,
 author = {Yamazaki, N. and Uhara, H. and Fukushima, S. and Uchi, H. and Shibagaki, N. and Kiyohara, Y. and Tsutsumida, A. and Namikawa, K. and Okuyama, R. and Otsuka, Y. and Tokudome, T.},
 issue = {5},
 journal = {CANCER CHEMOTHERAPY AND PHARMACOLOGY},
 month = {Sep},
 note = {Purpose<br/>Ipilimumab (IPI), a monoclonal antibody against immune-checkpoint receptor cytotoxic T lymphocyte antigen-4, is designed to enhance antitumor T cell function. IPI 10 mg/kg plus dacarbazine (DTIC) significantly improved overall survival in a phase 3 study involving predominantly Caucasian patients, with an adverse event (AE) profile similar to that of IPI monotherapy. We conducted a single-arm, phase 2 study to evaluate the safety and efficacy of IPI plus DTIC in Japanese patients.<br/>Methods<br/>Previously untreated patients with unresectable stage III or IV melanoma received IPI 10 mg/kg plus DTIC 850 mg/m2 every 3 weeks for four doses (q3w × 4), followed by DTIC q3w × 4 and then IPI every 12 weeks until disease progression or intolerable toxicity.<br/>Results<br/>All 15 treated patients reported drug-related AEs, the most common of which were increases in alanine aminotransferase (n = 12, 80 %) and aspartate aminotransferase (n = 11, 73 %). Treatment-related serious AEs were reported in 11 (73 %) patients. Nine patients (60 %) discontinued treatment due to drug-related toxicities. Immune-related AEs (irAEs) were reported in 14 patients (93 %). The most frequent irAEs were liver (n = 12, 80 %) and skin (n = 10, 67 %) toxicities. Five deaths were reported; all were caused by progressive disease. Efficacy evaluation showed one complete response, one partial response and four patients with stable disease. Best overall response rate was 13 % (2/15), and the disease control rate was 40 % (6/15). The study was terminated early due to frequent, high-grade liver toxicities.<br/>Conclusions<br/>IPI 10 mg/kg plus DTIC 850 mg/m2 was not considered tolerable in the Japanese patient population., Article, CANCER CHEMOTHERAPY AND PHARMACOLOGY.76(5):969-975(2015)},
 pages = {969--975},
 title = {Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma},
 volume = {76},
 year = {2015}
}