Palliative care: a supportive adjunct to pediatric phase I clinical trials for anticancer agents?

Abstract

Hampering enrollment of children to phase I oncology research would dramatically impair the ability of investigators to develop new treatments to improve medical care for the pediatric cancer population. The variability in pediatric tumor response indicates a need for the development of new anticancer agents that specifically target varying histologies of malignancies.1 Aleska and Koren argue that “clinical trials may be the only way to determine the appropriate types of treatments for pediatric cancer.”2 The primary scientific objectives of a phase I trial are to assess the safety and tolerability of tested agents, to identify the maximum-tolerated dose of the drug, and characterize the drug's pharmacokinetics.1,3–8 Secondarily, preliminary antitumor efficacy data are sought.1,3–8 However, enrolling children with cancer in phase I trials raises important ethical concerns. Although pediatric clinical investigators hope that participation in the phase I trials will help subjects, they are not meant to cure or even improve the condition of the child. Usually, however, they offer the only remaining treatment option for children with advanced cancer and thereby provide an important source of hope at a difficult time. Similar to adult phase I trials, pediatric phase I trials generally have a 5% to 8% response rate.1,3–8 Thus, it may be questionably unreasonable to offer enrollment in pediatric phase I trials because the likelihood of risk and discomfort are disproportionate to the marginal benefit. These trials may raise unrealistic hopes of a cure, burden already sick children with potentially invasive procedures, compound suffering through chemotherapeutic and other associated drug side effects, and limit the opportunity for palliation. On the other hand, families may perceive even a low likelihood of benefit favorably, and ethically we ought to respect the family's prima facie … Reprint requests to (C.M.U.) School of Nursing and Center for Bioethics, Room 357 NEB, 420 Guardian Dr, Philadelphia, PA 19104-6096. E-mail: culrich{at}nursing.upenn.edu