title: Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia.
abstract: A randomized clinical trial of combination chemotherapy for adult acute lymphoblastic leukemia (ALL) with doxorubicin, vincristine and prednisolone with and without L-asparaginase (AdVP vs L-AdVP) was conducted, involving 58 institutions throughout Japan. After reaching complete remission (CR), patients were treated with the same regimen for more than 2 years. Among 166 evaluable cases of the 198 cases enrolled, CR rates were 63.1% (53/84) with AdVP and 64.6% (53/82) with L-AdVP (P = 0.837). Median survival times and 7-year survival rates were 12.7 months and 21.2% with AdVP, and 16.0 months and 22.3% with L-AdVP (P = 0.955 by generalized Wilcoxon test [GW], P = 0.952 by log-rank test [LR]). Median disease-free survival times and 7-year survival rates were 13.5 months and 23.8% with AdVP and 17.0 months and 30.6% with L-AdVP, showing some increments for L-AdVP but no statistical significance (P = 0.141 by GW, P = 0.300 by LR). Among the cases of extramurally confirmed FAB subtypes, CR rates were 75.9% (63/83) for the L1 subtype and 51.3% (39/76) for the L2 subtype (P = 0.001). As to adverse effects, pancreatitis was complicated more frequently in L-AdVP than in AdVP (P = 0.039). Other side effects such as hyperbilirubinemia, diabetes mellitus, diarrhea and hypofibrinogenemia were observed more frequently with L-AdVP, but with no statistical significance. Thus, addition of a single course of L-asparaginase in the induction phase of combination chemotherapy with doxorubicin, vincristine and prednisolone did not significantly enhance the effect of antileukemic treatment of adult ALL.
authors.affiliation: Department of Internal Medicine, Chubu National Hospital, Obu, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Nagura
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Ota
authors.forename: T
authors.initials: T
authors.lastname: Maekawa
authors.forename: F
authors.initials: F
authors.lastname: Takaku
authors.forename: H
authors.initials: H
authors.lastname: Uchino
authors.forename: T
authors.initials: T
authors.lastname: Masaoka
authors.forename: I
authors.initials: I
authors.lastname: Amaki
authors.forename: K
authors.initials: K
authors.lastname: Kawashima
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D016009:Chi-Square Distribution; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011239:Prednisolone / Q000008:administration & dosage; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D011239:Prednisolone; D001215:Asparaginase