Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): implications for studies testing initial treatment of brain tumors.

PURPOSE: To determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma. METHODS AND MATERIALS: Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of > or =60, and adequate pulmonary function were eligible. All patients provided informed consent. Standard RT started within 5 weeks of diagnosis. In both arms, 150 mg/m(2) of TMZ was given on Days 1-5 of RT. In Arm 1, 200 mg/m(2) of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m(2) of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles. RESULTS: A total of 15 and 14 patients were enrolled in the two pilot arms. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose. CONCLUSION: The results of these pilot studies have implications for the design of studies testing the initial treatment of brain tumors. Because of the poor tolerance of the combination, the multicooperative group Phase III study consists of two randomized arms of single-agent carmustine vs. single-agent TMZ.

Gastrointestinal lymphoma.

Primary GI lymphoma is a rare clinical entity. A primary nodal tumor should be ruled out. Symptoms may not be localizing and B symptoms are less common. A tissue diagnosis, preferably by transmural biopsy for small intestinal involvement, often reveals a high-grade morphology. The staging work-up should include a bone marrow examination, although formal staging laparatomy is not always required. Patients with Mushoff stage IE or IIE1 disease do better than those with extraregional nodal disease or distant metastatic involvement. Surgical resection with clear margins is required in order to maximize the changes for cure. Chemotherapy or radiotherapy may give a survival advantage when used as adjuvant treatment for selected stage IE and IIE disease. Chemotherapy should be used after surgical debulking in more advanced disease in order to minimize the chance for bleeding or performation. Future randomized, multi-institutional trials will give more direction as to the best modes of management.