Phase II trial of temozolomide plus concurrent whole-brain radiation followed by TNV regimen as adjuvant therapy for patients with newly diagnosed primary CNS lymphoma.
BACKGROUND
Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin's lymphoma limited to the CNS. Treatment of PCNSL with high-dose methotrexate (HD-MTX)-based chemotherapy and whole-brain radiotherapy (WBRT) is associated with high rates of relapse and severe treatment-related neurotoxicity.


AIM
To report our experience of treating newly diagnosed PCNSL with temozolomide, nedaplatin, and vincristine (TNV), as the replacement of HD-MTX, in combination with concurrent chemoradiotherapy.


MATERIALS AND METHODS
Newly diagnosed PCNSL patients were given concurrent temozolomide (75 mg/m 2 , orally) daily during WBRT. Then, the TNV regimen was given after four weeks. The TNV regimen consisted of temozolomide (200 mg/m 2 orally: Days 1-5), nedaplatin (80 mg/m 2 intravenous: Day 1), and vincristine (1.4 mg/m 2 intravenous: Day 1). Each cycle was of a duration of four weeks and a maximum of six cycles were applied. The primary end point was response to treatment obtained by magnetic resonance imaging (MRI). Secondary end points were progression-free survival (PFS) and fewer toxic effects.


RESULTS
The study subjects included 14 patients (median age: 53.5, median Karnofsky Performance Scale (KPS): 75). The median number of TNV cycles given was five. RESPONSE TO TREATMENT: Complete response in 12 (85.7%) patients, partial response in 2 (14.3%) patients, and none with progressive disease. The objective response rate was 100%, and median PFS was 21.4 months. Toxicity was relatively mild, which mainly included nausea in six and fatigue in five, grade 3-4 hematotoxicity in one, and abnormal liver functions in five patients. No neurotoxicity has been observed till date.


CONCLUSION
The efficacy outcomes in this study are comparable to other reported HD-MTX-based regimens plus WBRT, with an added favorable toxicity profile. Prospective, randomized controlled trials are warranted to confirm such results.