A phase II study of a modified hyper-CVAD frontline therapy for patients with adverse risk diffuse large B-cell and peripheral T-cell non-Hodgkin lymphoma

Leuk Lymphoma. 2019 Apr;60(4):904-911. doi: 10.1080/10428194.2018.1516873. Epub 2018 Dec 14.

Abstract

To improve complete remission (CR) rates by reducing toxicity and enhancing delivery, we created a modified hyper-CVAD/MA regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone/methotrexate, cytarabine) by reducing the cytarabine dose (3 g/m2 to 2 g/m2) and number of cycles (eight to six). We conducted a phase II trial in the pre-rituximab era in the intermediate-high international prognostic index (IPI) (≥2) de novo diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL) (ACTRN12605000105640). CR rates were compared with reported IPI-stratified rates. Sixty-three patients (n = 26 PTCL; n = 37 DLBCL) were evaluated; median follow-up of 30 months. CR rates for PTCL and DLBCL patients were 46% and 49%, respectively, similar with reported CR rates with CHOP-like chemotherapy (p = .6). Of the patients, 51 (81%) experienced ≥1 unplanned hospital admission; only 41 (65%) completed six cycles. The cytarabine modifications did not prevent significant toxicity. Modified hyper-CVAD/MA resulted in similar outcomes to CHOP-like chemotherapy in aggressive lymphomas and was associated with significant toxicity.

Keywords: Aggressive non-Hodgkin lymphoma; clinical trial; hyper-CVAD.

Publication types

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

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cause of Death
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Dexamethasone / adverse effects
  • Dexamethasone / therapeutic use
  • Disease Progression
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, T-Cell, Peripheral / diagnosis
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Lymphoma, T-Cell, Peripheral / mortality
  • Male
  • Middle Aged
  • Recurrence
  • Remission Induction
  • Survival Analysis
  • Treatment Outcome
  • Vincristine / adverse effects
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Vincristine
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide

Supplementary concepts

  • CVAD protocol