Phase II-I-II study of two different doses and schedules of pralatrexate, a high-affinity substrate for the reduced folate carrier, in patients with relapsed or refractory lymphoma reveals marked activity in T-cell malignancies.

PURPOSE: To determine the maximum-tolerated dose (MTD) and efficacy of pralatrexate in patients with lymphoma. PATIENTS AND METHODS: Pralatrexate, initially given at a dose of 135 mg/m(2) on an every-other-week basis, was associated with stomatitis. A redesigned, weekly phase I/II study established an MTD of 30 mg/m(2) weekly for six weeks every 7 weeks. Patients were required to have relapsed/refractory disease, an absolute neutrophil greater than 1,000/microL, and a platelet count greater than 50,000/microL for the first dose of any cycle. RESULTS: The every-other-week, phase II experience was associated with an increased risk of stomatitis and hematologic toxicity. On a weekly schedule, the MTD was 30 mg/m(2) weekly for 6 weeks every 7 weeks. This schedule modification resulted in a 50% reduction in the major hematologic toxicities and abrogation of the grades 3 to 4 stomatitis. Stomatitis was associated with elevated homocysteine and methylmalonic acid, which were reduced by folate and vitamin B12 supplementation. Of 48 assessable patients, the overall response rate was 31% (26% by intention to treat), including 17% who experienced complete remission (CR). When analyzed by lineage, the overall response rates were 10% and 54% in patients with B- and T-cell lymphomas, respectively. All eight patients who experienced CR had T-cell lymphoma, and four of the six patients with a partial remission were positron emission tomography negative. The duration of responses ranged from 3 to 26 months. CONCLUSION: Pralatrexate has significant single-agent activity in patients with relapsed/refractory T-cell lymphoma.

The diminishing role of surgery in the treatment of gastric lymphoma.

OBJECTIVE: This article reviews the pathogenesis, diagnosis, and treatment of patients with primary gastric lymphoma, with special attention to the changing role of surgery. SUMMARY BACKGROUND DATA: Primary gastric lymphomas are non-Hodgkin lymphomas that originate in the stomach and are divided into low-grade (or indolent) and high-grade (or aggressive) types. Low-grade lesions nearly always arise from mucosa-associated lymphoid tissue (MALT) secondary to chronic Helicobacter pylori (H. pylori) infection and disseminate slowly. High-grade lesions may arise from a low grade-MALT component or arise de novo and can spread to lymph nodes, adjacent organs and tissues, or distant sites. METHODS: A review of the relevant English-language articles was performed on the basis of a MEDLINE search from January 1984 to August 2003. RESULTS: About 40% of gastric lymphomas are low-grade, and nearly all these low-grade lesions are classified as MALT lymphomas. For low-grade MALT lymphomas confined to the gastric wall and without certain negative prognostic factors, H. pylori eradication is highly successful in causing lymphoma regression. More advanced low-grade lymphomas or those that do not regress with antibiotic therapy can be treated with combinations of H. pylori eradication, radiation therapy, and chemotherapy. Nearly 60% of gastric lymphomas are high-grade lesions with or without a low-grade MALT component. These lymphomas can be treated with chemotherapy and radiation therapy according to the extent of disease. Surgery for gastric lymphoma is now often reserved for patients with localized, residual disease after nonsurgical therapy or for rare patients with complications. CONCLUSION: The treatment of gastric lymphoma continues to evolve, and surgical resection is now uncommonly a part of the initial management strategy.