Clinical outcome of high dose methotrexate-based vincristine and procarbazine combination chemotherapy without radiotherapy for patients with primary central nervous system lymphoma

Objective. We investigated the objective response rate to high dose methotrexate (HDMTX)-based vincristine and procarbazine combination chemotherapy without radiotherapy in primary central nervous system lymphoma (PCNSL) patients as a frontline therapy, and sought to identify factors that influence response to HDMTX-based vincristine and procarbazine combination therapy. Methods. Prospective observational analysis was performed on 109 newly diagnosed immunocompetent PCNSL patients. All patients received front-line chemotherapy of combined HDMTX (3.5 g/m2) and vincristine (1.4 mg/m2) for one day during weeks 1, 3, 5, 7, and 9, and procarbazine (100 mg/m2) for one week during weeks 1, 5, and 9 without radiotherapy. Results. Among the 109 patients, 94 patients with PCNSL who were registered at our institute from March 2003 to August 2013 were evaluated for participation in the study. Seventy-three patients (77.7%) achieved complete or partial remission after the first combined cycle without irradiation. Higher objective response rates were observed for patients with: 1) age < 60 years (p = 0.046); 2) Eastern Cooperative Oncology Group (ECOG) performance score of <2 (p = 0.022); 3) low risk status as defined by the International Extranodal Lymphoma Study Group (p = 0.004); 4) p53 positivity (p = 0.005); 5) XBP-1 negativity (p = 0.002); 6) MUM-1 negativity (p = 0.001); and 7) homogenous gadolinium enhancement in MR images (p = 0.045). Multivariate analysis showed that ECOG performance score of < 2 (p = 0.012), low risk status (p < 0.05), positivity for p53 (p = 0.027), negativity for XBP-1 (p = 0.023), positivity for MUM-1 (p = 0.008), homogenous gadolinium enhancement by MRI (p < 0.001), and response to HDMTX-combination chemotherapy (p < 0.001) were associated with longer progression-free survival, and ECOG performance score of < 2 (p = 0.009), low risk status (p < 0.05), negativity for XBP-1 (p = 0.028), homogenous gadolinium enhancement by MRI (p < 0.001), and response to HDMTX-combination chemotherapy (p < 0.001) were associated with longer overall survival. Conclusion. Our prospective observational study results suggest that PCNSL patients treated with HDMTX-based vincristine and procarbazine combination chemotherapy should have good clinical outcomes even without radiotherapy, which allows avoidance of radiotherapy-associated neurotoxicity.