Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia

Lancet. 2000 Jul 22;356(9226):285-90. doi: 10.1016/S0140-6736(00)02503-4.


Background: Many antileukaemic agents or their metabolites are inactivated by liver enzymes. Most anticonvulsant drugs induce drug-metabolising enzymes and thereby increase the clearance of anticancer agents. We investigated whether anticonvulsants compromise the efficacy of cancer chemotherapy.

Methods: We identified whom of 716 children treated consecutively for acute lymphoblastic leukaemia at a single academic hospital in the USA between 1984 and 1994 received treatment for 30 days or longer with anticonvulsants (phenytoin, phenobarbital, carbamazepine, or a combination) at the same time as antileukaemic therapy. Cox's proportional-hazards models were used to assess the prognostic significance of anticonvulsants on event-free survival and risk of haematological and central-nervous-system (CNS) relapse, with stratification for treatment protocol.

Findings: 40 (5.6%) of 716 patients received anticonvulsants. Use of these drugs was associated with age over 10 years (p=0.003), non-hyperdiploid leukaemia (p=0.031), and T-cell immunophenotype (p=0.022). After adjustment for age and ploidy, anticonvulsant therapy was significantly related to worse event-free survival (hazard ratio 2.67 [95% CI 1.50-4.76]; p=0.0009), haematological relapse (3.40 [1.69-6.88]; p=0.0006), and CNS relapse (2.90 [1.01-8.28]; p=0.047) among the 566 patients with B-lineage leukaemia. No such associations were seen among the 114 patients with T-cell leukaemia (p=0.61, 0.35, and 0.53, respectively). Faster clearance of teniposide (p=0.0001) and methotrexate (p=0.051), but not cytarabine (p=0.26) was found among patients receiving anticonvulsants.

Interpretation: Long-term anticonvulsant therapy increases the systemic clearance of several antileukaemic agents and is associated with lower efficacy of chemotherapy. Alternatives to enzyme-inducing anticonvulsants should be prescribed for patients receiving chemotherapy for acute lymphoblastic leukaemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Proportional Hazards Models
  • Time Factors
  • Treatment Outcome


  • Anticonvulsants