A Systematic Review of the Adverse Events of Imatinib Mesylate in the Treatment of Chronic Myeloid Leukemia.

Abstract

Imatinib mesylate was the first of a generation of tyrosine kinase inhibitors developed for the
treatment of cancer. The drug was designed to target the specific molecular abnormality found in
the overwhelming majority of patients with chronic myeloid leukaemia. Imatinib was licensed
on preliminary clinical data, which showed that it was effective in the treatment of chronic myeloid leukaemia and gastrointestinal stromal tumours, based on surrogate outcome measures.

This study aimed to systematically review the published literature of toxicities related to imatinib
mesylate in the treatment of chronic myeloid leukaemia. All literature describing adverse events were sought and assessed on their quality in relation to the question of interest. Two systematic reviews, one randomised controlled trial, 26 uncontrolled clinical trials and 56 case reports/series were included in the study. In addition to the profile of adverse events being presented, the study investigated factors that had the potential to influence the frequency of adverse events, such as
the dose of imatinib, the disease stage of the subjects under investigation, the previous treatment history of the patients and the duration of imatinib treatment.

The study found that the most common toxicities observed in clinical trials (controlled and
uncontrolled) were gastrointestinal toxicities (nausea, vomiting, diarrhoea), haematologic
problems (various cytopenias), musculoskeletal problems such as muscle cramps or musculoskeletal pain, and fluid retention. Case-reports reported dermatological events such as pigment changes and various rashes as the most common toxicities.

The study found that there was no significant influencing factor on the frequency of specific adverse events. A key observation of the thesis was the difficulty in making conclusive findings due to the quality of toxicity reporting by the study authors.

Date of Award	Feb 2006
Original language	English
Awarding Institution	Aston University