PROMACE-MOPP and intrathecal chemotherapy for CNS lymphomas

Abstract

We conducted a Phase II study of PROMACE-MOPP and intrathecal (IT) therapy followed by cranial radiation in 7 patients (4 male, 3 females) with diffuse large cell lymphomas (including one T cell) involving the central nervous system (CNS). Median age was 47 years (range, 25–78). Median performance status was 2 (range, 2 to 3). Two patients had positive CSF cytology. No patients had prior chemotherapy or radiotherapy. Treatment consisted of PROMACE (cyclophosphamide 650 mg/m2, Adriamycin 25 mg/m2, etoposide 120 mg/m2 days 1 and 8, methotrexate (MTX) 1.5 g/m2 and folinic acid 50 mg/m2 (× 5) day 15, and prednisone 60 mg/m2 days 1–14) × 3–4 courses. MOPP consisted of mustargen 6 mg/m2 and vincristine 1.4 mg/m2 days 1 and 8, procarbazine 100 mg/m2 and prednisone 40 mg/m2 po days 1–14 × 3–4 courses. IT drugs were MTX 20 mg and hydrocortisone 20 mg day 1 and cytosine arabinoside 100 mg day 8, courses 2 to 6, or more frequently if CSF cytology was positive. Following MOPP, 4000 cGy whole brain radiation (XRT) and 2000 cGy boost was given. Response was evaluated before XRT Two patients declined XRT, 3 declined MOPP and 2 declined IT drugs. Two patients had extracerebral disease and 5 were primary CNS lymphomas. Response after PROMACE was CR: 3 patients; PR 2: stable 1. One patient, with extracerebral disease, experienced PR in the abdomen and CR by CT scan in the brain, but had persistent positive CSF cytology. This patient died from pneumocystis pneumonia 10 weeks after her last CSF cytology and 17 weeks after her diagnosis. After PROMACE +/- MOPP 6 patients experienced CR's. Median (range) survival was 100 (17–334) weeks, with 1 patient lost to follow up at 32 weeks. Toxicity included febrile neutropenia; 6 patients; pneumocystis pneumonia: 1 (fatal); thrombocytopenia; 5; stomatitis: 3; diarrhea; 2; nausea; 3. Conclusion: This regimen is active in the treatment of CNS lymphomas, although toxicity is substantial.