title: Japanese phase II study of rituximab maintenance for untreated indolent B-cell non-Hodgkin lymphoma with high tumor burden.
abstract: Recent large-scale randomized clinical trials in Europe and the US demonstrated that maintenance therapy with rituximab significantly improved the progression-free survival (PFS) in indolent B-cell non-Hodgkin lymphoma (B-NHL) patients, especially those with follicular lymphoma (FL). However, rituximab maintenance has not been approved in Japan, because there are no clinical data supporting the benefit of rituximab maintenance in Japanese patients. Therefore, we conducted a single-arm, multicenter bridging study in previously untreated indolent B-NHL patients with high tumor burden. The primary endpoint was 4-year PFS and was expected to be 70 % based on previous studies. Sixty-two patients, including 55 FL patients, were enrolled and received induction therapy with CHOP combined with rituximab (R-CHOP). Fifty-eight patients responding to R-CHOP induction received rituximab at 375 mg/m2every 8 weeks for 2 years as for the rituximab maintenance arm in the PRIMA study. A 4-year PFS of 69.8 % was obtained (95 % confidence interval 55.9-80.0 %). Rituximab maintenance was well tolerated and common adverse events were infections, neutropenia, and/or leukopenia that were manageable with conventional supportive care. No patients died. These data were compatible with the PRIMA data. R-CHOP induction followed by rituximab is useful in Japanese patients with untreated indolent B-NHL having high tumor burden. Clinical trial number UMIN000001191.
authors.affiliation: Division of Hematology/Oncology, Gunma Cancer Center, 617-1 Takabayashinishicho, Ohta, 373-8550, Japan. taigarash@gunma-cc.jp.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.|Department of Hematology, Tokai Central Hospital, Kakamigahara, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Department of Hematology, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Department of Hematology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.affiliation: Department of Hematology/Oncology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Hematology, Hiroshima University School of Medicine, Hiroshima, Japan.|Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Hematology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan.|Department of Palliative Care, Saga Prefectural Hospital Koseikan, Saga, Japan.
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tomita
authors.affiliation: Department of Hematology, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Department of Hematology, National Hospital Organization, Hokkaido Cancer Center, Sapporo, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Kurosawa
authors.affiliation: The University of Tokyo, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Radiology, International University of Health and Welfare Mita Hospital, Tokyo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nawano
authors.affiliation: Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan.|Department of Nuclear Medicine, Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Terauchi
authors.affiliation: Faculty of Science and Engineering, Chuo University, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.affiliation: Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D000069283:Rituximab / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Non-Hodgkin lymphoma; Phase II clinical trial; Progression-free survival; Rituximab maintenance