Cancer incidence in a trial of an antiapoptotic agent for Parkinson's disease

Mov Disord. 2010 Sep 15;25(12):1801-8. doi: 10.1002/mds.23006.

Abstract

We performed a placebo-controlled trial of CEP-1347, an inhibitor of neuronal apoptotic cell death, in patients with early Parkinson's disease (PD) to determine whether long-term therapy would slow disability progression. This also provided an opportunity to monitor cancer incidence in a large cohort of PD patients followed prospectively including periods before and after patients developed disability requiring dopaminergic therapy. This was a multicenter study of 806 patients with early PD, without disability requiring dopaminergic therapy, assigned randomly to placebo or one of three doses of CEP-1347. Patients were monitored for an average of 1.8 years (1,467 patient-years) with routine cancer screening evaluations and annual skin examinations by a dermatologist. There was no significant excess of cancers among patients taking CEP-1347 compared with placebo for any cancer type (all P > 0.1). Nonmelanoma skin cancers were the most common cancer type observed. The incidence of melanomas was 20.9 times that predicted in the general population. Most melanomas occurred in patients who had never taken dopaminergic therapy. We found no evidence that CEP-1347 affected cancer incidence within 2 years of follow-up. Melanoma occurrence in our PD patients was greater than predicted compared with the general population and was unrelated to dopaminergic therapy. Clinical surveillance of PD patients for melanoma may be warranted.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carbazoles / adverse effects*
  • Carbazoles / therapeutic use
  • Chi-Square Distribution
  • Comorbidity
  • Disease Progression
  • Double-Blind Method
  • Follow-Up Studies
  • Humans
  • Incidence
  • Longitudinal Studies
  • Middle Aged
  • Neoplasms / epidemiology*
  • Neoplasms / etiology*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / epidemiology*

Substances

  • Carbazoles
  • 3,9-bis((ethylthio)methyl)-K-252a