title: Influence of dose reduction of vincristine in R-CHOP on outcomes of diffuse large B cell lymphoma.
abstract: Dose intensity (DI) of chemotherapy affects prognosis of diffuse large B cell lymphoma (DLBCL). Myelotoxicity is the major dose-limiting toxicity (DLT) of most cytotoxic agents for hematological malignancies, whereas DLT of vincristine (VCR) is mainly neurological toxicity. Although VCR is a key drug and its combination with other cytotoxic agents needs consideration, studies focused on relative DI (RDI) of VCR have not been done before. We retrospectively analyzed 86 cases of DLBCL that received six or more cycles of cyclophosphamide (CPM), doxorubicin (DXR), VCR, prednisolone, and rituximab [R-CHOP] and calculated RDI of each cytotoxic agent to analyze its influence on treatment outcome. The median RDI of CPM, doxorubicin, and VCR was 80.0, 81.7, and 78.4 %, respectively (p = 0.002). The average RDI (ARDI) of these three agents was 80.0 %. The overall survival was significantly worse in the low ARDI (<85 %) than in the high ARDI (>85 %) group (2-year survival rate 67.2 vs 93.4 %, p = 0.011). The survival rate with low RDI VCR (<85 %) was lower than that with high RDI VCR (>85 %), even when the remaining two agents had high ARDI (2-year survival rate 74.3 vs 95.8 %, p = 0.047). In conclusion, VCR dose tended to be reduced compared with CPM and DXR in R-CHOP. Lower ARDI of cytotoxic agents and lower RDI of VCR could lead to poor prognosis in the treatment of DLBCL with R-CHOP. We thought these observations should be confirmed in a prospective study.
authors.affiliation: Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita, 286-8523, Japan. yutsu@naritasekijyuji.jp.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Utsu
authors.affiliation: Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita, 286-8523, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takaishi
authors.affiliation: Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita, 286-8523, Japan.
authors.forename: Shunichirou
authors.initials: S
authors.lastname: Inagaki
authors.affiliation: Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita, 286-8523, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Arai
authors.affiliation: Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita, 286-8523, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yuasa
authors.affiliation: Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita, 286-8523, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita, 286-8523, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsuura
authors.affiliation: Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita, 286-8523, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Aotsuka
authors.affiliation: Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita, 286-8523, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Wakita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Chemotherapy; Diffuse large B cell lymphoma; Dose intensity; R-CHOP; Vincristine