Affiliation:
1. Takashi Ishida, Hiroshi Inagaki, and Ryuzo Ueda, Nagoya City University Graduate School of Medical Sciences; Kazuhito Yamamoto, Aichi Cancer Center; Michinori Ogura, Nagoya Daini Red Cross Hospital, Nagoya; Tatsuro Joh and Masao Tomonaga, Japanese Red Cross Nagasaki Genbaku Hospital; Shinichiro Yoshida, Nagasaki Medical Center; Kunihiro Tsukasaki, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Science, Nagasaki; Naokuni Uike, National Kyushu Cancer Center; Toshihiro...
Abstract
Purpose Adult T-cell leukemia-lymphoma (ATL) is usually resistant to conventional chemotherapies, and there are few other treatment options. Because CC chemokine receptor 4 (CCR4) is expressed on tumor cells from most patients with ATL, KW-0761, a humanized anti-CCR4 monoclonal antibody, which markedly enhances antibody-dependent cellular cytotoxicity, was evaluated in the treatment of patients with relapsed ATL. Patients and Methods A multicenter phase II study of KW-0761 for patients with relapsed, aggressive CCR4-positive ATL was conducted to evaluate efficacy, pharmacokinetic profile, and safety. The primary end point was overall response rate, and secondary end points included progression-free and overall survival from the first dose of KW-0761. Patients received intravenous infusions of KW-0761 once per week for 8 weeks at a dose of 1.0 mg/kg. Results Of 28 patients enrolled onto the study, 27 received at least one infusion of KW-0761. Objective responses were noted in 13 of 26 evaluable patients, including eight complete responses, with an overall response rate of 50% (95% CI, 30% to 70%). Median progression-free and overall survival were 5.2 and 13.7 months, respectively. The mean half-life period after the eighth infusion was 422 ± 147 hours (± standard deviation). The most common adverse events were infusion reactions (89%) and skin rashes (63%), which were manageable and reversible in all cases. Conclusion KW-0761 demonstrated clinically meaningful antitumor activity in patients with relapsed ATL, with an acceptable toxicity profile. Further investigation of KW-0761 for treatment of ATL and other T-cell neoplasms is warranted.
Publisher
American Society of Clinical Oncology (ASCO)
Cited by
538 articles.
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