Authors: Marie-France Demierre, MD, FRCPC, Vernon K. Sondak, MD

Abstract

Background: Chemoprevention refers to the use of agents to reverse, suppress, or prevent carcinogenic progression of cancer. The use of chemoprevention is an unexplored strategy in melanoma prevention.
Methods: A retrospective review of the literature was undertaken regarding the important elements in evaluating chemoprevention as a strategy in melanoma.
Results: Several considerations need to be addressed before a chemoprevention agent can be moved to a large randomized trial. Statins have both experimental and epidemiologic evidence to support their further development as candidate chemopreventive agents, but the evidence is insufficient to justify large-scale phase III studies. A strong scientific rationale, a systematic approach to chemoprevention agent development with rigorous chemoprevention designs, and careful selection of surrogate endpoint biomarkers are critical issues in developing a chemoprevention strategy.
Conclusions: Addressing these relevant considerations will allow for the development of chemoprevention in melanoma.

Introduction

Chemoprevention of melanoma has been suggested as an unexplored strategy in melanoma.[1] Chemoprevention refers to the use of agents to treat cancer by reversing, suppressing, or preventing its carcinogenic progression.[2] The prerequisites for this approach in melanoma have been reviewed,[1,3] and statins, the lipid-lowering drugs, have been suggested as promising chemoprevention agents.[4]

The completion of large clinical cancer chemoprevention trials has raised awareness of the importance and potential of this approach to cancer control.[5] However, to date, results have been mixed. In breast cancer, tamoxifen has been a successful chemoprevention agent, fulfilling the three levels of chemoprevention, although the risks of endometrial cancer have tempered the enthusiasm and opened the door for newer agents. In other settings, large randomized trials based on epidemiologic observations have yielded disappointing results in cervical cancer[6] and colorectal cancers,[7] as well as adverse results from beta carotene supplementation in smokers.[8] The considerations that have resulted from these negative trials are relevant to all cancer chemoprevention strategies.[9] Attention to these issues is needed before chemoprevention of melanoma can become a reality. In particular, a strong scientific rationale, a systematic approach to chemoprevention agent development[9] with rigorous chemoprevention designs,[10] and careful selection of surrogate endpoint biomarkers are critical.