Abstract
We previously conducted a phase 1 study of bortezomib, doxorubicin and intermediate-dose dexamethasone (iPAD) therapy and determined the optimal dose of bortezomib to be 1.0 mg/m2. We then conducted a multicenter phase 2 study in patients with relapsed or refractory myeloma. Bortezomib 1.0 mg/m2 was administered intravenously on days 1, 4, 8 and 11, in combination with intravenous doxorubicin 9 mg/m2 on days 1–4, and dexamethasone 20 mg orally on days 1–2, 4–5, 8–9 and 11–12 at a 3-week interval for six cycles. The primary endpoint of this study was the complete remission (CR) rate, and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Twenty-seven patients, median age of 63, were enrolled. An overall response rate was 89 % with CR rate of 30 %. The median PFS time was 12.1 months, and the median OS time was not reached. One patient died of pneumonia. Although the incidence of hematological toxicities was high, these were transient and manageable. The most common non-hematological toxicity was sensory neuropathy; grade 3 toxicity was observed in six patients (22 %) and treatment was discontinued in four. We conclude that iPAD therapy is feasible, and shows efficacy by inducing high response rates and long response duration.
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Acknowledgments
This clinical study was registered in University hospital Medical Information Network (registration number; UMIN000001210), and was supported by Grant-in-Aid for Scientific Research (23501318) and the non-profit organization of Clinical Hematology/Oncology Treatment Study Group (CHOT-SG). There was no financial disclosure from any authors. We thank project managers Ms. Y. Ito and N. Gushima, and secretaries Ms. E. Kumakawa and N. Ikoma for valuable assistance in conducting the present study, and the medical staff of the following institutions for participating in this study; T. Toyota, Y. Ikari, H. Sasaki, K. Ishitsuka (Fukuoka University), T. Ochi, Y. Meguri, T. Kuroi, J. Konishi (Okayama Medical Center), T. Fujisaki (Matsuyama Red Cross Hospital), N. Nomura, N. Kitamura, H. Yasuyama, J. Tsukada (University of Occupational and Environmental Health), Y. Mori, Y. Abe, T. Teshima (Kyushu University), K. Aoki (Kyushu Kosei-nenkin Hospital), D. Nakamura, M. Yoshimitsu (Kagoshima University), S. Murakami, M. Kugimiya (Kumamoto University), I. Choi, N. Uike (Kyushu Cancer Center), T. Eto, K. Takase, T. Saito (Hamanomachi Hospital), E. Otsuka (Oita Prefectural Hospital), M. Ogata (Oita University), M. Hidaka, T. Sakae (Kumamoto Medical Center), H. Matsuoka (Koga General Hospital), Y. Masaki, M. Miki (Kanazawa Medical University), J. Suzumiya (Shimane University), K. Nagafuji (Kurume University), S. Makino (Toranomon Hospital), and S. Aoki (Niigata University).
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Takamatsu, Y., Sunami, K., Muta, T. et al. Bortezomib, doxorubicin and intermediate-dose dexamethasone (iPAD) therapy for relapsed or refractory multiple myeloma: a multicenter phase 2 study. Int J Hematol 98, 179–185 (2013). https://doi.org/10.1007/s12185-013-1389-6
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DOI: https://doi.org/10.1007/s12185-013-1389-6