Studies on the chemotherapy in acute leukemia Part I. Induction therapy with Neocarzinostatin alone

Neocarzinostatin (NCS) is an antitumor antibiotic isolated from streptomyces carzinostaticus by Ishida et al. in Japan in 1957. The chemical structure of NCS is a single chain made of acidic polypeptide consisting of 112 amino acids. Its antitumor activities have been demonstrated in various experimental tumors. Its mode of action is considered to inhibit DNA synthesis at early stage of S phase and to block it at G(2) phase. The agent has been used clinically for solid tumors without remardable effects, although never been used in treating human leukemia. For the first time the author has given NCS alone to patients with acute leukemia in the dose ranging from 0.04-0.06 mg/kg/day for 4-5 days as one course of treatment. In case no sufficient remission was induced further courses of treatment were repeated after an internal of 4-10 days, and obtained the following results. 1) Of 18 cases 7 (38.9%) attained complete remission and 4 (22.2%) partial remission. 2) Complete remission was obtained even in the patients with refractory varieties of acute leukemia, i.e., acute promyelocytic leukemia, monocytic leukemia and leukemia in aged group. 3) No noteworthy side effects other than occasional nausea or anorexia were observed and suppression on normal hematopoiesis was very slight. From these results it can be concluded that NCS is one of the most potent antileukemic agents for inducing remission in acute leukemia

Studies on the chemotherapy in acute leukemia Part II. Induction therapy with Neocarzinostatin combined by other drugs

In an attempt to improve the chemotherapy of acute leukemia in adults, the author has studied the induction therapy on 63 cases with acute leukemia with Neocarzinostatin (NCS; N) in combination with conventional antileukemic agents; Vincristine (V), Daunorubicin (D), Cytosine Arabinoside (A), 6-Mercaptopurine-Riboside (M) and Prednisolone (P). Eighteen cases with acute lymphocytic leukemia (ALL) was treated with protocol A (NVMP, NDMP, NAMP). Out of 45 cases with acute non-lymphocytic leukemia (ANLL), 25 was treated with protocol A and 20 treated with protocol B (NADP, NAVP), and obtained the following results. 1) Of all 63 cases 51 (81.6%) attained complete remission and 9 (14.3%) partial remission. 2) Complete remission was obtained in 15 cases (83.3%) out of 18 with ALL and 36 cases (80.0%) of 45 with ANLL; the latter cases with ANLL consisted of 18 of 25 cases (72.0%) treated with protocol A and 18 of 20 cases (90.0%) with protocol B. 3) Refractory varieties included cases with acute myelogenous leukemia who had passed through atypical hematological findings, cases with monocytic leukemia, cases with WBC count over 50,000 per μl or with nucleated cell count in bone marrow over 500,000 per μl before treatment and cases over 50 years old. 4) In this induction therapy with NCS in combination, antileukemic effects was remarkable, while suppression on normal hematopoiesis, especially on thrombocytes, was very slight. 5) As to the other side effects no noteworthy disturbances other than occasional nausea, anorexia and liver damage in protocol B were observed. From these results it can be concluded that NCS in combination is one of the most potent remission induction therapies in acute leukemia in adults