All-oral metronomic DEVEC schedule in elderly patients with peripheral T cell lymphoma

Cancer Chemother Pharmacol. 2020 Dec;86(6):841-846. doi: 10.1007/s00280-020-04172-3. Epub 2020 Oct 18.

Abstract

Purpose: Peripheral T cell lymphomas (PTCLs) have an overall poor prognosis. Indeed, registry data in elderly patients show that the median progression-free survival (mPFS) following first- and second-line therapies are only 6.7 and 3.1 months, respectively. The aim of the study is to show the activity of metronomic chemotherapy, a regular administration of low chemotherapeutic drug doses allowing a favourable toxicity profile, on elderly PTCL patients.

Methods: We report a series of 17 PTCL patients, treated with the all-oral metronomic schedule DEVEC (prednisolone-etoposide-vinorelbine-cyclophosphamide) in four Italian centres. Patients 5/17 (29.4%) were treatment-naïve (naïve) and 12/17 (70.6%) were relapsed-refractory (RR), respectively. The median age was 83 years (range 71-87) and 71.5 years (range 56-85) for naïve and RR, respectively. In vitro activity of metronomic vinorelbine (VNR), etoposide (ETO) and their concomitant combination on HH, a PTCL cell line, was also assessed.

Results: Histology: PTCL-not-otherwise-specified = 12; angioimmunoblastic = 2; NK/T nasal type = 1; adult-type leukaemia lymphoma = 1, transformed Mycosis Fungoides = 1. The overall response rate was 80 and 58% in naïve and RR, respectively; whereas the PFS was 20 in naïve (95% CI 0-43) and 11 months (95% CI 4.2-17.8) in RR. The occurrence of relevant adverse events was 23.5%, which was managed with ETO dose reduction. In vitro experiments showed that both metronomic VNR and ETO caused a significant inhibitory activity on HH cells and a strong synergism when administered concomitantly.

Conclusion: All-oral DEVEC showed an encouraging activity and acceptable toxicity. This schedule deserves further studies in elderly PTCL also for assessing combinations with targeted drugs.

Keywords: Cyclophosphamide; Etoposide; Low dose; Metronomic chemotherapy; Peripheral T cell lymphoma; Prednisolone; Prognosis; Vinorelbine.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Metronomic*
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cell Line, Tumor
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Drug Resistance, Neoplasm
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Humans
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Lymphoma, T-Cell, Peripheral / mortality
  • Lymphoma, T-Cell, Peripheral / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Organic Chemicals / administration & dosage
  • Organic Chemicals / adverse effects
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Progression-Free Survival
  • Prospective Studies
  • Vinorelbine / administration & dosage
  • Vinorelbine / adverse effects

Substances

  • Organic Chemicals
  • deltacortene
  • Etoposide
  • Cyclophosphamide
  • Vinorelbine
  • Prednisone