NEW YORK (Reuters Health) Oct 19 - The SMILE protocol (the steroid dexamethasone along with methotrexate, ifosfamide, L-asparaginase and etoposide) is effective against extranodal natural killer/T-cell lymphoma, nasal type (ENKL), a new study shows.
"Most tumors of NK-cells express multidrug resistance associated P-glycoprotein, and therefore do not respond to conventional chemotherapy," Dr. Ritsuro Suzuki, senior author on a report of the study, told Reuters Health by email.
Dr. Suzuki of Nagoya University Graduate School of Medicine in Japan and colleagues note that resistance is at partly responsible for the fact that patients usually survive less than a year if they're treated with conventional chemotherapy for aggressive lymphomas, such as cyclophosphamide, doxorubicin, vincristine, and prednisone.
"SMILE chemotherapy includes P-glycoprotein unrelated agents and resulted in dramatic improvement of tumor response against NK-cell lymphoma," said Dr. Suzuki.
He added, "The extranodal NK-cell lymphoma accounts for 3% of all lymphoma in Japan, but 0.2 to 0.3% in Caucasians. The incidence in Asian immigrants in the US seems almost the same as that in East Asia."
Because this lymphoma is so rare, the need for a specific treatment wasn't recognized, Dr. Suzuki said. "Approximately 600 Japanese and 200 US people develop this lymphoma in a year. These patients need a completely different strategy from other lymphomas."
To test the SMILE combination, the researchers enrolled 38 patients in a phase II study, including 20 who were newly diagnosed with stage IV, 14 with a first relapse, and four with primary refractory disease.
Two patients died early of grade 5 infection, and the entry criteria were revised to require lymphocyte counts of 500/microliter or more, the research team reported online October 11th in the Journal of Clinical Oncology.
There were no further treatment-related deaths, but 92% of patients developed grade 4 neutropenia. Infection (in 61%) was the most common grade 3 or 4 non-hematologic complication.
After two cycles of treatment, the overall response rate was 79% and the complete response rate was 45%. Of the 28 patients who completed the protocol treatment, 19 underwent hematopoietic stem-cell transplantation. They seemed to show better overall survival and progression-free survival, but the difference was not statistically significant.
Following the two-cycle protocol treatment, 21 patients received up to four additional courses. The median follow-up time of surviving patients was 24 months, with a range of 13 to 35 months. Overall one-year survival was 55%. This, say the investigators, is much better than what previous treatments could achieve.
"SMILE," added Dr. Suzuki, "will contribute to improve the poor prognosis of NK-cell lymphoma and leukemia."
Nevertheless, the researchers warn doctors to watch vigilantly for myelosuppression and infection, and they say full-dose administration of SMILE should be avoided for patients in poor condition.
"The SMILE regimen," they conclude, "is potentially toxic, and careful patient monitoring is needed."
SOURCE: http://bit.ly/pZnL5E
J Clin Oncol 2011.
"Most tumors of NK-cells express multidrug resistance associated P-glycoprotein, and therefore do not respond to conventional chemotherapy," Dr. Ritsuro Suzuki, senior author on a report of the study, told Reuters Health by email.
Dr. Suzuki of Nagoya University Graduate School of Medicine in Japan and colleagues note that resistance is at partly responsible for the fact that patients usually survive less than a year if they're treated with conventional chemotherapy for aggressive lymphomas, such as cyclophosphamide, doxorubicin, vincristine, and prednisone.
"SMILE chemotherapy includes P-glycoprotein unrelated agents and resulted in dramatic improvement of tumor response against NK-cell lymphoma," said Dr. Suzuki.
He added, "The extranodal NK-cell lymphoma accounts for 3% of all lymphoma in Japan, but 0.2 to 0.3% in Caucasians. The incidence in Asian immigrants in the US seems almost the same as that in East Asia."
Because this lymphoma is so rare, the need for a specific treatment wasn't recognized, Dr. Suzuki said. "Approximately 600 Japanese and 200 US people develop this lymphoma in a year. These patients need a completely different strategy from other lymphomas."
To test the SMILE combination, the researchers enrolled 38 patients in a phase II study, including 20 who were newly diagnosed with stage IV, 14 with a first relapse, and four with primary refractory disease.
Two patients died early of grade 5 infection, and the entry criteria were revised to require lymphocyte counts of 500/microliter or more, the research team reported online October 11th in the Journal of Clinical Oncology.
There were no further treatment-related deaths, but 92% of patients developed grade 4 neutropenia. Infection (in 61%) was the most common grade 3 or 4 non-hematologic complication.
After two cycles of treatment, the overall response rate was 79% and the complete response rate was 45%. Of the 28 patients who completed the protocol treatment, 19 underwent hematopoietic stem-cell transplantation. They seemed to show better overall survival and progression-free survival, but the difference was not statistically significant.
Following the two-cycle protocol treatment, 21 patients received up to four additional courses. The median follow-up time of surviving patients was 24 months, with a range of 13 to 35 months. Overall one-year survival was 55%. This, say the investigators, is much better than what previous treatments could achieve.
"SMILE," added Dr. Suzuki, "will contribute to improve the poor prognosis of NK-cell lymphoma and leukemia."
Nevertheless, the researchers warn doctors to watch vigilantly for myelosuppression and infection, and they say full-dose administration of SMILE should be avoided for patients in poor condition.
"The SMILE regimen," they conclude, "is potentially toxic, and careful patient monitoring is needed."
SOURCE: http://bit.ly/pZnL5E
J Clin Oncol 2011.
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