Mitoxantrone and high-dose cytarabine as salvage therapy for refractory non-Hodgkin's lymphoma

Article Abstract:

The use of sequential chemotherapy since 1977 has improved the rates and duration of remission from non-Hodgkin's lymphoma (NHL). In this type of treatment, a flexible number of cycles of primary combinations of drugs is followed by a flexible number of cycles of a secondary different drug combination, which is chosen according to clinical response. This type of treatment is based on the idea that lymphoma cells develop resistance to single drugs and then can multiply, while combinations of drugs are more effective in eliminating more cells before resistance can occur. Patients who do not respond to sequential chemotherapy tend to have a poor outcome. Mitoxantrone has been useful in the treatment of NHL, and high-dose, but not low-dose, cytarabine (Ara-C) has been useful against NHL. The effectiveness of the combination of mitoxantrone and Ara-C in NHL that has become resistant to other drug combinations has been studied. The dose of Ara-C was 3 grams per square meter of body surface area, while mitoxantrone was given in doses of 10 milligrams per square meter. Complete remissions were achieved in 6 of 18 patients with high-grade malignant NHL, and in 1 of 13 patients with intermediate or low-grade NHL. Partial remissions were achieved in 2 of 18 with high-grade disease and in 5 of 13 with low-grade disease. This yielded a total response rate of 45 percent, very good results for patients with such poor prognosis. The time to relapse was from 4 to 17 months, with an average of 7 months. The most serious side effect of therapy was an increased incidence of infections due to suppression of bone marrow (which produces infection-fighting white blood cells), with 63 percent of patients requiring hospital treatment of infections. Other side effects were mild and included nausea, stomatitis (mouth inflammation), and rapid heartbeat. Because of its beneficial effects and good tolerance, further investigation of mitoxantrone with higher doses of Ara-C in treating non-Hodgkin's lymphoma is warranted. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Mitoxantrone/high dose ara-C and recombinant human GM-CSF in the treatment of refractory non-Hodgkin's lymphoma: a pilot study

Article Abstract:

A previous study showed that the combined drug regimen of the anticancer agents mitoxantrone and ara-C was active against non-Hodgkin's lymphoma (NHL) a cancer of the lymphatic system, which was unresponsive to conventional chemotherapy (refractory). However, increasing doses of this regimen, referred to as NOAC, caused myelosuppression, inhibition of bone marrow function. Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) is a protein that activates the production of macrophages, immune cells produced in bone marrow that are capable of ingesting foreign particles. This protein can be produced in large quantities by recombinant technology and the final product is called recombinant human GM-CSF (rhGM-CSF). The effects of rhGM-CSF after NOAC treatment were assessed in 23 patients with refractory NHL and compared with the response of 14 patients who received only NOAC. A severe decrease in neutrophils (a type of white blood cell) and in platelets (cells involved in blood clotting) lasted longer in patients receiving NOAC alone than in patients receiving both rhGM-CSF and NOAC. Patients treated with rhGM-CSF developed fewer infections and stomatitis, inflammation of the mouth, than patients not receiving the factor. Treatment with rhGM-CSF was associated with accumulation of fluids in the lung and abdominal cavities in five patients; the formation of blood clots in two patients; bone pain in two patients; and respiratory distress syndrome (severe breathing impairment) in one patient. A complete remission was achieved in 9 of 23 patients treated with rhGM-CSF and in 2 of 14 patients not treated with the factor. Patients treated with rhGM-CSF survived longer than patients receiving chemotherapy alone. The findings show that rhGM-CSF shortens the period of blood cell suppression, reduces the incidence of stomatitis, and causes few adverse effects. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug therapy, Bone marrow cells, Granulocyte-macrophage colony stimulating factor

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Successful treatment of adult acute lymphoblastic leukemia after relapse with prednisone, intermediate-dose cytarabine, mitoxantrone, and etoposide (PAME) chemotherapy

Article Abstract:

The success rate in the treatment of adults with acute lymphoblastic leukemia is far from satisfactory; only 25 to 40 percent of patients treated with initial chemotherapy may be expected to achieve long-term survival. Among those who relapse, less than half may be expected to achieve remission a second time, and few of these patients will survive. Various drugs are known to be effective against leukemia, albeit at high doses. In an attempt to improve the success of treating relapsed patients, a combination treatment was designed to include four different anti-leukemic drugs, each at its optimum efficacy-to-toxicity ratio. Forty-three adult patients with relapsed or unresponsive acute lymphoblastic leukemia were treated with a combination of prednisone, cytarabine, mitoxantrone, and etoposide. The combination, dubbed PAME, produced a complete remission in 30 of 43 patients. The median duration of the remission was short for these patients, however, at four months, and the median overall survival for the patients achieving complete remission was seven months. (Consumer Summary produced by Reliance Medical Information, Inc.)

Evaluation, Prednisone, Lymphocytic leukemia, Chemotherapy, Combination, Combination chemotherapy, Acute leukemia, Etoposide

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