High Doses of Chemotherapy Drug Lead to Better Survival for Children with Leukemia and Lymphoma
Higher doses of a common chemotherapy drug, methotrexate, may lead to less recurrences of a certain type of leukemia and lymphoma in children. In a report issued from the annual meeting of the American Society of Clinical Oncology in San Franciso (see the meeting abstract), researchers from the Pediatric Oncology Group (POG) reported that children with either T-cell acute lymphoblastic leukemia (T-ALL) or advanced T-cell lymphoblastic non-Hodgkins lymphoma (T-NHL) live longer after receiving high doses of methotrexate as part of their cancer treatment.
Barbara Asselin, M.D., from the University of Rochester in New York, presented the results from this Phase III clinical trial, which took place in multiple cancer centers across the country. The study enrolled 441 children with either T-ALL or T-NHL and randomly assigned them to receive either standard treatment with the usual doses of methotrexate or standard treatment with high doses of methotrexate. All patients also received leucovorin, a drug to help decrease the side effects of methotrexate, as well as radiation treatments to the brain to help lessen the risk of developing cancer there.
Patients on the low-dose regimen were less likely to have gone into remission by the end of the initial part of chemotherapy, called induction (16 high-dose patients compared to 8 regular-dose patients). Among those patients who did go into remission, patients on the regular dose were also more likely to have relapsed by the end of the trial: 29 children compared with 15 children had their cancer return when receiving the standard doses of the drug. The majority of cancer recurrences showed up in the brain tissues.
Three years after treatment, 86 percent of the children on the higher doses of methotrexate had not relapsed compared with 72 percent of children on the standard doses. Side effects from methotrexate include seizures, low blood counts, infection and mouth sores. Patients receiving higher doses of methotrexate were more likely to have severe mouth sores.
While "patients [did] better than expected" on the high dose treatment, stated Asselin, better treatments for these high-risk patients are needed. She suggested new drugs or targeted immunotherapy "may provide the missing link" for therapy in these patients.
Leukemias and lymphomas are two of the three most common cancers seen in children, accounting for more than 50 percent of childhood disease. T-cell lymphocytes, a normal part of the immune system, can sometimes develop into cancer. Cancers growing from these T-cells tend to be more difficult to treat and cure. The treatments are very rigorous, often taking a year to complete. Additionally, side effects from some of the drugs can cause long-term problems. The study also looked at whether a drug called dexrazoxane can prevent damage to the heart caused by doxorubicin, a drug commonly used to treat childhood leukemia and lymphoma. Results from this part of the study are not yet available.
Malcolm Smith, M.D., from the Cancer Therapy Evaluation Program at the National Cancer Institute, led a discussion of this study and commented that while these "are very promising early results, the exact survival rates may change over time" and longer follow-up of these patients is needed.
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