Temozolomide as salvage treatment in primary brain lymphomas.

Methotrexate (MTX)-based chemotherapy extends survival in patients with primary brain lymphomas, but it is not clear whether multiagent chemotherapy is superior to MTX alone. Treatment options for patients with recurrent primary brain lymphoma are limited; there is no standard second-line chemotherapy. New chemotherapeutic agents with clear activity in brain lymphoma are needed for treatment of recurrent disease. We report the results of a phase II trial assessing activity of the alkylating agent temozolomide in immunocompetent patients with recurrent primary brain lymphomas, previously treated with high-dose MTX-containing chemotherapy and/or radiotherapy. A median of two courses (range 1-12) of temozolomide 150 mg m-2 day-1, for 5 days every 4 weeks was administered to 36 patients yielding nine complete and two partial responses (response rate: 31%; 95% confidence interval 16-46%). One-year survival was 31% (95% confidence interval 16-46%). Toxicity was negligible. We conclude that temozolomide is active in recurrent primary brain lymphomas and should further be evaluated in this disease, perhaps in combination with MTX as initial treatment.

Gemcitabine, ifosfamide, oxaliplatin and rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a pilot study.

BACKGROUND: The prognosis of patients with aggressive non-Hodgkin's lymphoma (NHL) relapsing or progressing after front-line therapy remains poor. Since high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) can cure a proportion of such patients, provided that a substantial tumor shrinkage is achieved, the development of more effective and less toxic salvage regimens remains a major challenge. We evaluated the clinical activity, toxicity and mobilizing capacity of a new salvage regimen, which combines gemcitabine and oxaliplatin with ifosfamide and rituximab (R-GIFOX) in patients with relapsed and refractory CD20(+) NHL. PATIENTS AND METHODS: Patients were scheduled to receive three courses of therapy followed by mobilization and ASCT or three more courses if ineligible for ASCT. R-GIFOX consisted of rituximab (375 mg/m(2) on day 1), gemcitabine (1000 mg/m(2) on day 2), oxaliplatin (130 mg/m(2) on day 3) and ifosfamide (5 g/m(2) on day 3) as a 24-h single infusion in patients aged < or =65 years, or fractionated over 3 days (days 3-5) in patients aged >65 years. Treatment was given every 2 weeks with G-CSF support (5 microg/kg/day or 10 microg/kg/day at the end of the third course for stem cell mobilization). Responses were evaluated by the integrated FDG-PET/IWC criteria after the third course and at the end of the entire program. RESULTS: Fourteen patients (median age 63 years, range 37-78 years) with relapsed (n = 9) or primary progressive (n = 5) aggressive (diffuse large cell, mantle cell, follicular G3), advanced (stage IV 71%), poor risk (IPI 3-5 50%) NHL were accrued in this pilot study. Patients had received a median of two previous treatment lines (range 1-4). The median number of R-GIFOX courses delivered was 4 (range 1-6). Thirteen patients completed at least three courses of therapy and were evaluable for response. The overall response rate assessed after three courses of R-GIFOX was 77%, with seven complete responses and three partial responses. Effective CD34(+) cell mobilization was obtained in four of six eligible patients and two had ASCT. Hematologic and extra-hematologic toxicity was tolerable. Failure-free survival was 79.6% at median follow-up of 6 months (range 2-12). Molecular remissions were documented in two patients with mantle cell NHL. CONCLUSIONS: Based on the results of this pilot study, we conclude that the R-GIFOX regimen is feasible, tolerable, effective and able to mobilize peripheral stem cells in patients with relapsed and refractory aggressive NHL.

MATILDE regimen followed by radiotherapy is an active strategy against primary CNS lymphomas.

The authors assessed MATILDE chemotherapy followed by response-tailored radiation therapy in 41 patients aged 70 years or younger with primary CNS lymphoma in a Phase II trial. With response rates of 76% after MATILDE and 83% after chemotherapy with or without radiation therapy, this was an active strategy, particularly in low- to intermediate-risk patients (International Extranodal Lymphoma Study Group [IELSG] score). Myelosuppression was the dose-limiting toxicity, with 9.5% of lethal complications. After a median follow-up of 49 months, a plateau in the survival curve (5-year overall survival: 41 +/- 7%) was obtained.

CEOP/PEB alternating chemotherapy in advanced intermediate and high-grade non-Hodgkin's lymphomas.

BACKGROUND AND METHOD: From February, 1987 to July, 1990, 28 patients (M/F = 16/12; median age = 60.5 yrs) affected by intermediate (22) or high-grade (6) advanced stage (III = 8; IV = 20) NHL were given a median (range 4-10) of 8 cycles of CEOP (Cyclophosphamide, Epirubicin, Vincristine and Prednisone), alternated every 21 days with PEB (Cisplatin, Etoposide, Bleomycin). RESULTS: Nineteen (68%) pts. achieved a CR, 5 (18%) a PR, and 4 (14%) experienced progressive disease (PD); 11/19 CRs subsequently relapsed within a median (range 3-15) time of 8 mos.. After a follow-up ranging from 6 to 42+ (median 18) mos., the 3-year actuarial overall survival (OS) was 51% and shifted to 18% at 42 mos. After 7-42+ (median 19) mos., 14/19 (73%) Crs were still alive with 63% of them predicted to survive at 3 years. The projected 3-year disease-free survival (DFS) for these pts. after 1-36+ (median 8) mos. was 28%. DISCUSSION: CEOP/PEB alternating chemotherapy failed to improve the therapeutic results we obtained in a previous study with CEOP alone. Toxicity was moderate, but higher than expected.

Chronic lymphocytic leukaemia and neuroendocrine cancer.

We report a unique association between neuroendocrine cancer and chronic lymphocytic leukaemia (CLL) in a 63-year-old man. Neuroendocrine cancer was resistant to various conventional treatments and following locoregional progression we treated the patient with hypoxic pelvic perfusion of cisplatin 100 mg/m2 plus mitomycin 40 mg/m2, using the stopflow method, for three cycles: a dramatic and surprising reduction of > 75% in the evaluable lesions was observed. The cumulative effect of treatment produced a complete response from CLL. At cytogenetic examination the neuroendocrine cells were diploid, whereas CLL cells showed trisomy 12. Moreover, deletion of the short arm of chromosome 3 was found in both neoplastic populations. Whether the abnormality seen on chromosome 3 in the two diseases represents a critical event is not known.