The toxic and antineoplastic effects of guinea pig serum L‐asparaginase have been investigated. The enzyme is active against early (0 day) through late (24 day) 6C3HED subcutaneous tumors in C3H mice but whole guinea pig serum in the same doses was not at all effective against intracerebral tumors comprising the same cells. Whole guinea pig serum caused no acute toxic effects in mice with small tumors. No toxic effects were seen after administration of a partially purified L‐asparaginase (PPLAFI) in C3H mice with small tumors from 0 to 2 days or in monkeys during 9 days of observation. Profuse diarrhea was observed in mice with massive tumors after PPLAFI treatment, during tumor regression. The effects of PPLAFI are described in a human with leukemia.
Cis-dichlorodiammineplatinum (CDDP) and VM26, both of which have been proven efficient in treating neuroblastoma, were combined in a sequential schedule and administered to 22 children with disseminated neuroblastomas resistant to treatment with cyclophosphamide and doxorubicin (Adriamycin). During this same study, 14 children were prospectively evaluated for the effect of CDDP on magnesium metabolism and the effect of the induced hypomagnesemia on parathyroid function. Complete or partial tumor responses were achieved in six and nine cases. Respectively and were of prolonged duration (longer than six months) in eight of the 15 responding. It was also shown that CDDP-induced hypomagnesemia is the result of excessive renal loss and is severe enough to interfere with the normal parathormone response to hypocalcemia.
One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.
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