Background: Standard temozolomide has been shown to be active in progressive low grade gliomas after surgery, whereas few data are available on the impact of dose dense regimens. Thus, we developed a phase II single arm multicenter study to evaluate the efficacy and toxicity of a regimen of dose dense temozolomide in progressive low grade oligodendroglial tumors. Methods: The inclusion criteria of the study were as follows: 1)biopsy-proven supratentorial WHO grade II oligodendroglioma and oligoastrocytoma; 2)progressive disease, clinically (epileptic seizures)or radiologically; 3)measurable disease on MRI (at least 1 cm); 4)age ≥18 years; 5)Karnofsky Performance Status ≥70. Temozolomide was administered at 150mg/m2 1 week on/1 week off up to a maximum of 18 cycles or unacceptable toxicity. The primary end-point was response rate (RR) according to RANO criteria, whereas secondary end-points were clinical benefit in terms of reduction of epileptic seizures ≥50%, progression-free survival (PFS), quality of life and toxicity. Results: From January 2005 until December 2010 60 patients (median age 39 and median KPS 80) have been accrued and are now evaluable for response. Response rates on T2/FLAIR images were as follows: CR 0/60, PR 21/60 (35%), MR 14/60 (23%), SD 21/60 (35%) and PD 4/60 (7%). The clinical benefit was significant in 29/34 patients (85%). As for toxicity 5/60 (8%) patients stopped treatment for lymphopenia grade IV, whereas 11/31 patients (35%) were switched to the standard regimen of temozolomide. PET with methionine was added to MRI in 17 patients: in 10/17 (59%) a disappearance or a significant reduction of uptake was observed, being the reduction of seizures better correlated with the response on PET rather than that on MRI. 1p/19q codeletion was not associated with either the response or the clinical benefit, whereas the analysis of MGMT methylation and IDH1 mutations are ongoing. Thirty-nine (65%) patients are still free of tumor progression. Conclusions: Dose-dense TMZ seems to be active, especially in terms of clinical benefit, but the myelotoxicity could be a concern.