A randomized clinical trial of combination chemotherapy for adult acute lymphoblastic leukemia (ALL) with doxorubicin, vincristine and prednisolone with and withoutL-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 diseasefree 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.
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Baccarani M, Corbelli G, Amadori S, Drenthe-Schonk A, Willemze R, Meloni G, et al (1982) Adolescent and adult acute lymphoblastic leukemia: prognostic features and outcome of therapy, a study of 293 patients. Blood 60: 677
Brearley RL, Johonson SAN, Lister TA (1979) Acute lymphoblastic leukemia in adults: clinicopathological correlations with the French-British-American Co-operative Group Classification. Eur J Cancer 15: 909
Champlin R, Gale RP (1989) Acute lymphoblastic leukemia: recent advances in biology and therapy. Blood 73: 2051
Cremer P, Lakomek M, Beck W, Prindull G (1988) The effect ofL-asparaginase on lipid metabolism during induction chemotherapy of childhood lymphoblastic leukemia. Eur J Pediatr 147: 64
Gottlieb AJ, Weinberg V, Ellison RR, Henderson ES, Terebelo H, Rafla S, et al (1984) Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by cancer and acute leukemia group B. Blood 64: 267
Gugliotta L, DÁngelo A, Belmonte MM, Viganò-DÁngero S, Colombo G, Catani L, et al (1990) Hypercoagulability during L-asparaginase treatment: the effect of antithrombin III supplementation in vivo. Br J Haematol 74: 465
Hoelzer D, Thiel E, Löeffler H, Büchner T, Ganser G, Heil G, et al (1988) Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71: 123
Hussein KK, Dahlberg S, Head D, Waddell CC, Dabich L, Weick JK, et al (1989) Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy. Blood 73: 57
Jones B, Holland JF, Clindewell O, Jacquillat C, Weil M, Pochèdly C, et al (1977) Optimal use ofL-asparaginase in acute lymphocytic leukemia. Med Pediatr Oncol 3: 387
Kawashima K, Takeshima H, Higashi Y, Hamaguchi M, Sugie H, Imamura I, et al (1991) High efficacy of monomethoxypolyethylene glycol-conjugatedL-asparaginase (PEG2-ASP) in two patients with hematological malignancies. Leukemia Res 15: 525
Kimura K (1965) Chemotherapy of acute leukemia with special reference to criteria for evaluation of therapeutic effect. In: Advances in chemotherapy of acute leukemia. A seminar on Chemotherapy of Acute Leukemia under the US-Japan Cooperative Science Program, Bethesda Md, 27–28 September 1965, p 21
Leimert JT, Burns CP, Wiltse CG, Armitage JO, Clarke WR (1980) Prognostic influence of pretreatment characteristics in adult acute lymphoblastic leukemia. Blood 56: 510
Linker CA, Levitt LJ, O'Donnell M, Ries CA, Link MP, Forman SJ, et al (1987) Improved results of adult acute lymphoblastic leukemia. Blood 69: 1242
Murakami H, Hiraoka A, Nagura E, Hamajima N, Yamada K, Kimura K (1988) Multivariate analysis of factors associated with prognosis for adult acute leukemia. Acta Haematol Jpn 51: 1607
Nagura E, Yamada K (1985) A controlled randomized clinical trial of adult acute leukemia. Jpn J Clin Hematol 26: 821
Oettgen HF, Stephenson PA, Schwartz MK, Leeper RD, Tallal L, Tan CC, et al (1970) Toxicity of E. coliL-asparaginase in man. Cancer 25: 253
Ortega JA, Nesbit ME, Donaldson MH, Hittle RE, Weiner J, Karoh M, et al (1977)L-Asparaginase, vincristine and prednisone for induction of first remission in acute lymphocytic leukemia. Cancer Res 37: 535
Rodeghiero F, Castaman G, and Dini E (1990) Fibrinopeptide A changes during remission induction treatment withL-asparaginase in acute lymphoblastic leukemia: evidence for activation of bleeding coagulation. Thromb Res 57: 31
Schauer P, Arlin ZA, Mertelsmann R, Cirrincione C, Friedman A, Gee TS, et al (1983) Treatment of acute lymphoblastic leukemia in adults: results of the L-10 and L-10 M protocols. J Clin Oncol 1: 462
This work was supported by a grant-in-aid from the Japanese Foundation for Multidisciplinary Treatment of Cancer (Co-operative Project no. 2)
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Nagura, E., Kimura, K., Yamada, K. et al. Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia. Cancer Chemother. Pharmacol. 33, 359–365 (1994). https://doi.org/10.1007/BF00686263
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