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
O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Hematological toxicity, notably
thrombocytopenia often limits adequate exposure.