Intermediate-dose cytosine arabinoside and amsacrine: an effective regimen with low toxicity in refractory acute nonlymphocytic leukemia

Article Abstract:

Cytosine arabinoside has improved the treatment of patients with acute nonlymphocytic leukemia (ANLL). However, in the effective high-dose range, the drug is particularly toxic, and contributes to the early death rate of 20 to 30 percent. High-dose cytosine arabinoside affects the liver, lungs, nervous system, gastrointestinal tract, and skin. Preliminary results have indicated that an intermediate dose of cytosine arabinoside combined with amsacrine could avoid the toxic effects of cytosine arabinoside while effecting a good response from poor-risk patients with ANLL. To confirm and expand this finding, the combination was used in the treatment of 32 patients with ANLL and five with chronic myelogenous leukemia. Nineteen ANLL patients had relapsed after previous treatment with cytosine arabinoside, 6-thioguanine, and daunorubicin; the remainder had failed to respond to first-line treatment. The patients received amsacrine, 150 milligrams per square meter of body area daily for three days, and 500 milligrams per square meter cytosine arabinoside every 12 hours for five days. Both doses were infused over an hour's time. Among the patients with ANLL, complete relapses were achieved in 58 percent of the patients, a result that compares with high-dose cytosine arabinoside. The regimen was well tolerated, and there were no serious side effects. The patients with chronic myelogenous leukemia, all of whom were in the blastic phase, did not fare as well; there were no responses observed in this group. The results indicate that intermediate-dose cytosine arabinoside and amsacrine is an effective treatment for acute nonlymphocytic leukemia that has relapsed or been refractory to first-line treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

Care and treatment, Nonlymphoid leukemia, Myeloid leukemia, Amsacrine

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High-dose cytosine arabinoside in relapsed and refractory non-Hodgkin's lymphoma

Article Abstract:

The prognosis is poor for patients with intermediate and high grade non-Hodgkin's lymphoma (NHL) who are resistant to multiple drug chemotherapy and for patients who relapse after chemotherapy. A second course of treatment with chemotherapy can produce complete remission in approximately 35 percent of the patients. However, most of these individuals eventually relapse and die from NHL. There are reports of patients with NHL who were treated with chemoradiotherapy and bone marrow transplantation who had disease-free survival rates of 20 to 50 percent. Patients who respond well to the chemotherapy treatment before transplantation, appear to do better after transplantation. A study was conducted with patients with relapsed NHL or NHL which was not responsive to chemotherapy (refractory NHL), who were treated with high doses of cytosine arabinoside (Ara-C). Ten out of 48 patients had a partial remission and 5 had a complete remission. Bone marrow transplantation was performed on those who responded to treatment. Seventy five percent of the patients suffered from toxicity from the Ara-C treatment, which resulted in fever and also destroyed blood cells, causing a decrease in the number of neutrophils and platelets. Twenty one percent of the subjects developed infections; 10 percent developed neurologic complications. Fifteen percent of the patients died as a result of the therapy. High doses of Ara-C are not recommended as therapy for patients with relapsed NHL or refractory NHL. The usefulness of Ara-C, in combination with other agents, needs to be further explored. (Consumer Summary produced by Reliance Medical Information, Inc.)

Prognosis, Antineoplastic agents, Bone marrow, Bone marrow transplantation, Non-Hodgkin's lymphomas

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Treatment of refractory Hodgkin's disease with high-dose cytosine arabinoside and mitoxantrone in combination

Article Abstract:

Hodgkin's disease has been potentially curable for over 20 years. Even patients diagnosed with advanced stage disease, such as stages IIIB to IVB, may achieve long-term disease-free survival rates of 50 to 60 percent. However, the prognosis remains dismal for those patients who fail to respond to initial chemotherapy. Since high-dose cytosine arabinoside and mitoxantrone (the so-called ''HAM'' protocol) is an intensive chemotherapeutic regimen that has been effective in refractory non-Hodgkin's lymphomas and acute leukemias, the protocol was evaluated in the treatment of 32 patients with Hodgkin's lymphoma, who had failed to respond to the standard initial treatment. The disease of all patients ranged from Stage III to Stage IVB at the time of initial treatment. Eighteen patients responded to treatment with the HAM protocol, five completely. Four patients died of infections attributable to the immune suppression following the chemotherapy. Of the 18 responding patients, 10 were given bone marrow transplantation. Two died as consequence of the transplant. A total of 10 of the original 32 patients remain alive, indicating that the treatment protocol has some effect. But the benefits of the treatment are not clearly superior to those of more mild treatments, so that the harsh HAM protocol is, in its present form, of limited applicability. Future studies, however, will determine if modification of the timing of treatment or the addition of growth factors to the regimen will reduce toxicity and retain effectiveness. (Consumer Summary produced by Reliance Medical Information, Inc.)

Patient outcomes, Mortality, Hodgkin's disease, Mitoxantrone hydrochloride, Mitoxantrone

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