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Forty-five previously-untreated adult patients with acute myelogenous leukemia (AML) were treated with N'-behenoyl-l-B-Darabinofuranosyl-cytosine (BHAC) in a multi-institutional cooperative study. Among 41 evaluable patients, 15 (36.6%) achieved complete remission (CR) and 10 (24.4%) achieved partial remission by daily administration of 3 to 8 mg/kg of BHAC. Higher daily doses (5 mg/kg or more) produced higher CR rates, and all of the CR were observed among the patients receiving a top1 BHAC dosage of 50 mg/kg or more in a period of 10 days or more. The side effects were mild and acceptable: nausea-anorexia was observed in 27% of the patients and vomiting in 17%. The results of this study thus indicate BHAC to be effective for remission induction of AML, and to deserve further clinical trials in combination with other anti-leukemic drugs.

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.

Aclarubicin was evaluated in combination chemotherapy for adult acute myeloid leukemia in a randomized trial involving 58 institutions throughout Japan. Behenoyl cytosine arabinoside (BH-AC).daunorubicin, 6-mercaptopurine, and prednisolone (DMP) was compared with BH-AC.aclarubicin, 6-mercaptopurine, and prednisolone (AMP). In the 360 evaluable cases among the 433 cases enrolled, complete remission (CR) rates were 63.7% (116/182) for BH-AC.DMP and 53.9% (96/178) for BH-AC.AMP (P = 0.0587). Median survival periods and 7-year survival rates were 15.8 months and 19.3% for BH-AC.DMP and 9.5 months and 20.2% for BH-AC.AMP (P = 0.0091 according to the generalized Wilcoxon test [GW], P = 0.196 according the log-rank test [LR]). Median disease-free survival periods were 15.4 months for BH-AC.DMP and 14.1 months for BH-AC.AMP (P = 0.851 by GW, P = 0.439 by LR). Among the 346 cases of extramurally confirmed FAB subtypes, CR rates were 67.9% (19/28) with BH-AC.DMP and 31.8% (7/22) with BH-AC.AMP for subtype M3 (P = 0.011) and 63.3% (93/147) with BH-AC.DMP and 56.8% (84/148) with BH-AC.AMP (P = 0.254) for subtypes M1, M2, M4, and M5. Diarrhea, ileus, pneumonia, and renal failure were more frequent with BH-AC.AMP than with BH-AC.DMP. The results indicate, at least on the basis of the long-term outcome, that BH-AC.AMP has antileukemic effects on subtypes M1, M2, M4, and M5 that are comparable with those of BH-AC.DMP.

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