Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

BACKGROUND: Standardized salvage treatment has not yet proved effective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide. METHODS: Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100-75 mg m(2)) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m(2)) every 3 weeks for < or =1 year. RESULTS: Forty-three patients (29 M, 14 F; median age 51 years, range 34-68; median KPS 90) were enrolled. Progression-free survival at 6 months (PFS-6) was 20.9% (95% CI: 9-33%); three patients (7.1%) had partial response (PR); 15 (34.9%), disease stabilization (SD). The median survival was 6 months (95% CI: 5-7). MGMT promoter status was methylated in 8 (18.6%) and unmethylated in 26 (60.5%) and not assessable in 9 (20.9%) patients, respectively. Disease control was 75% versus 34.6% in methylated and unmethylated MGMT patients (P = 0.044); no significant difference was found between groups for PFS-6 and survival. Grade 3 and 4 thrombocytopenia and neutropenia were observed in 20.9 and 16.3% of patients, during the induction phase, and in 0 and 9.5% patients during the maintenance phase, respectively. CONCLUSIONS: The findings of the present trial, that evaluate fotemustine in a homogeneous population, may represent a new benchmark for nitrosourea activity. Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide.

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.

Chemotherapy of advanced gastric cancer: a study of 43 consecutive cases treated with fluorouracil, adriamycin and mitomycin C (FAM).

All consecutive patients with advanced gastric carcinoma who came to the Oncology Dept. of the "L. Pierantoni Hospital" in Forlì, between June 1, 1980 and August 30, 1983, were treated with 5-fluorouracil, adriamycin and mitomycin C (FAM). None of the patients had previously received chemotherapy. The dominant location of metastasis was the liver in 21 pts (48.8%), the abdomen in 15 pts (34.8%) and distant organs in 7 pts (16.2%). The schedule of FAM regimen used was: 5 Fluorouracil, 600 mg/m2, days 1, 8, 29, 36; Mitomycin C 10, mg/m2, day 1; Adriamycin, 30 mg/m2, days 1, 29. Complete remission (CR) was reached in 2 pts (4.6%) with a median length of response (m.l.r.) of 55 weeks (range 20-90), partial remission (PR) in 9 pts (20.9%) with a m.l.r. of 15.1 weeks (2.2-60), no change (N.C.) in 19 pts (44%) with a m.l.r. of 10 weeks (2.2-54) and progression (P) in 13 pts (30.2%). Median survival of patients in CR + PR considered together was 48 weeks (12 months), for the NC pts 20 weeks (5 months) and for those in P 14.1 weeks (3.5 months). The authors reached the conclusion that gastric carcinoma may be treated with FAM both for palliation and to improve survival even if in a small number of patients.

Primary gastric lymphoma: a review of 45 cases.

Primary gastric lymphoma accounts for about 2% of gastric neoplasms. The prognosis of patients affected with non-Hodgkin's gastric lymphoma appears better than for other lymphatic sites. In a retrospective study, the authors have analyzed 45 patients, by evaluating the histopathologic characteristics and relative prognostic factors. The main factors significantly influencing 5-yr survival are: serosal penetration (31.17% vs. 71.2%, P less than 0.05), regional lymph node involvement (53.07% vs. 68%), and clinical stage of disease (IE: 85.6%, IVE:10%, P less than 0.001). The histologic characteristics, the high or low grade of malignancy, and patient age can also be considered important prognostic factors, but not statistically significant in our series of cases. Comparison between overall survival and disease-free survival of patients in stages IE and IIE who underwent surgery alone, with those who had chemotherapy and/or radiotherapy after surgery shows a higher survival (85.6%) of the group who had combined treatments, even though this difference is not statistically significant.

Prognostic significance of large mediastinal involvement in Hodgkin's disease.

Relapse rates of 75 patients with previously untreated Hodgkin's disease with stages I and II nodular sclerosis were analyzed according to the mediastinal involvement. The overall relapse rate was 22.6%. The probability of relapse was much greater for patients with large mediastinal involvement (66.6%) compared with 17% for patients with small mass, and 11.7% of patients without mediastinal involvement (P less than 0.001). There was no significant difference in recurrence rates between patients without mediastinal mass and patients with a small mass, and in these patients adjuvant chemotherapy MOPP after radiotherapy showed an evident benefit in reducing the relapse rate. On the other hand, no beneficial effect of adjuvant chemotherapy was observed in patients with large mediastinal involvement. Finally, in the 17 relapsing patients, 'salvage' chemotherapy was less effective in patients with large mediastinal mass than in those with small or no mediastinal involvement.