Anti-MGMT monoclonal antibody, clone 999DU33.3.5

Glioblastomas are the most common malignant primary intrinsic brain tumors. Their incidence increases with age, and males are more often affected. First-line management includes maximum safe surgical resection followed by involved-field radiotherapy plus concomitant and six cycles of maintenance temozolomide chemotherapy. Standards of care at recurrence are much less well defined. Minorities of patients are offered second surgery or re-irradiation, but data on a positive impact on survival from randomized trials are lacking. The majority of patients who are eligible for salvage therapy receive systemic treatment, mostly with nitrosourea-based regimens or, depending on availability, bevacizumab alone or in various combinations. In clinical trials, lomustine alone has been increasingly used as a control arm, assigning this drug a standard-of-care position in the setting of recurrent glioblastoma. Here we review the activity of lomustine in the treatment of diffuse gliomas of adulthood in various settings. The most compelling data for lomustine stem from three randomized trials when lomustine was combined with procarbazine and vincristine as the PCV regimen in the newly diagnosed setting together with radiotherapy; improved survival with PCV was restricted to patients with isocitrate dehydrogenase-mutant tumors. No other agent with the possible exception of regorafenib has shown superior activity to lomustine in recurrent glioblastoma, but activity is largely restricted to patients with tumors with O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Hematological toxicity, notably thrombocytopenia often limits adequate exposure.

Objective: Temozolomide has shown a significant anti-proliferative activity on adrenocortical cancer (ACC) cells in vitro. Design: On the basis of these results the drug was prescribed as second/third line in advanced metastatic ACC patients in four referral centers in Italy. Methods: We retrospectively collected anagraphic, clinical and pathological data of patients with advanced ACC with disease progression to standard chemotherapy plus mitotane who were treated with temozolomide at the dose of 200 mg/m(2)/die given for 5 consecutive days every 28 days. The primary endpoint was the disease control rate, defined as objective response or disease stabilization after 3 months. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and drug safety. Results: Twenty-eight patients have been included in the study. Ten patients (35.8%, 95% CI: 17.8-53.8) obtained a disease control from temozolomide treatment. In particular, 1 patient had a complete response, 5 patients a partial response and 4 patients stable disease. Median PFS was 3.5 months and median OS was 7.2 months. Disease response was more frequently observed in patients with methylation of O6-methylguanine-DNA methyltransferase (MGMT) gene. Temozolomide therapy was well tolerated and most toxicities were limited to grade G1-2 according to WHO criteria. @ Conclusion: Temozolomide was found active in the management of advanced ACC patients. The disease control rate obtained, however, was short-lived and the prognosis of treated patients was poor.