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

Br J Haematol. 2015 Mar;168(5):663-70. doi: 10.1111/bjh.13195. Epub 2014 Oct 15.

Abstract

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 60 years with relapsed/refractory DLBCL, not candidates for autologous stem cell transplantation, were treated R-CVEP [R 375 mg/m(2) intravenously (IV), day 1; C 600 mg/m(2) IV days 1, 8: E 70 mg/m(2) IV day 1, 140 mg/m(2) days 2, 3 orally (PO); V (300 vs. 400 mg) PO and P 60 mg/m(2) PO days 1-10] every 28 d for six cycles. Quality of life (QoL) was assessed in addition to response. Thirty patients (median age 76 years, 69-88) were enrolled (one died before treatment). Maximum tolerated dose (MTD) for V was 300 mg. 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 17·5 months. Median progression-free survival was 9·2 months. 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.

Keywords: combination; diffuse large B-cell lymphoma; elderly; relapsed/refractory; vorinostat.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Autografts
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Humans
  • Hydroxamic Acids / administration & dosage
  • Hydroxamic Acids / adverse effects
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Maximum Tolerated Dose
  • Palliative Care*
  • Prednisolone / administration & dosage
  • Prednisolone / adverse effects
  • Recurrence
  • Rituximab
  • Stem Cell Transplantation
  • Survival Rate
  • Vorinostat

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Hydroxamic Acids
  • Rituximab
  • Vorinostat
  • Etoposide
  • Cyclophosphamide
  • Prednisolone