Overcoming drug resistance in mantle cell lymphoma using a combination of dose-dense and intense therapy

Cancer Invest. 2010 Jul;28(6):654-60. doi: 10.3109/07357901003631015.

Abstract

We present a study of the prevalence of genetic polymorphisms and expression of genes encoding the drug-resistance proteins glutathione S-transferases (GSTs) in order to gain insights into the pattern of failure evident in mantle cell lymphoma. We note a high preponderance of genetic alterations conferring resistance to standard chemotherapy in this illness. Concurrent with this investigation, we present a series of patients who were provided dose-dense and intense chemotherapy to circumvent these drug-resistance mechanisms. High responses were noted, though durable remissions were few, indicating non-traditional chemotherapy options are important to investigate in this illness.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carmustine / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / genetics*
  • Etoposide / administration & dosage
  • Female
  • Gene Frequency
  • Glutathione S-Transferase pi / genetics
  • Glutathione Transferase / genetics*
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Humans
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / enzymology
  • Lymphoma, Mantle-Cell / genetics
  • Lymphoma, Mantle-Cell / mortality
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Peripheral Blood Stem Cell Transplantation
  • Polymorphism, Genetic*
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Phytogenic
  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Etoposide
  • Cyclophosphamide
  • Mitoxantrone
  • glutathione S-transferase T1
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Carmustine