Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation.

The standard treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in frail elderly patients has not been established. A variation was made on rituximab (R), cyclophosphamide (C), etoposide (E), procarbazine and prednisone (P), substituting vorinostat (V) for procarbazine. Patients aged 60years with relapsed/refractory DLBCL, not candidates for autologous stem cell transplantation, were treated R-CVEP [R 375mg/m(2) intravenously (IV), day 1; C 600mg/m(2) IV days 1, 8: E 70mg/m(2) IV day 1, 140mg/m(2) days 2, 3 orally (PO); V (300 vs. 400mg) PO and P 60mg/m(2) PO days 1-10] every 28d for six cycles. Quality of life (QoL) was assessed in addition to response. Thirty patients (median age 76years, 69-88) were enrolled (one died before treatment). Maximum tolerated dose (MTD) for V was 300mg. For 23 patients at MTD (six phase I+17 phase II), two were discontinued for toxicity, one withdrew consent, eight achieved complete response (35%), five achieved partial response (22%) and seven progressed (25%). Median overall survival was 175months. Median progression-free survival was 92months. Nine patients are alive. QoL declined during treatment but improved above baseline for patients who completed treatment. In conclusion, R-CVEP was tolerated at MTD and produced durable responses with improved QoL.