Palifermin in Prevention of Head and Neck Cancer Radiation-Induced Mucositis: Not Yet a Definitive Word on Safety and Efficacy Profile

TO THE EDITOR: We read with great interest the two reports on palifermin in the prevention of mucositis induced by postoperative or definitive chemoradiotherapy in patients with head and neck cancer. They address the unmet need of prevention of this debilitating adverse effect. However, in our opinion, there are some limitations of the studies that should be stressed. The authors correctly underlined that safety data regarding palifermin on patient outcome should be interpreted with caution, because the sample sizes were chosen only to address the primary end points. We would emphasize this lack of safety data by adding two more considerations. First, erythropoiesis stimulating agents were allowed to deal with severe anemia, although their role can be detrimental to outcome in patients with head and neck cancer. A possible imbalance in the use of erythropoiesis stimulating agents between the two arms could have had an impact on outcome. Second, half of the patients included in both trials had oropharyngeal tumors without stratifying for human papillomavirus positivity. This could have severely biased outcome analysis because of the favorable prognosis of human papillomavirus– positive patients. Interestingly, the benefit of palifermin in physician-assessed mucositis in both trials was not paralleled by a better patient-reported outcome (PRO), assessed through the mouth and throat soreness score. Generally, adverse events reported by physicians are less accurate than those reported by PRO instruments. Indeed, for mucositis, some clinicians have proposed replacing physician scales with patientassessed mucositis reporting. Although mouth and throat soreness scores have been shown to be comparable to clinician assessment of mucositis, the same PRO in a randomized trial with palifermin in hematopoietic stem-cell transplantation anticipated the onset, peak, and resolution of mucositis assessed by clinicians. These data would imply that for the present studies, the most sensitive instrument was not able to detect any difference. Thus, we fully share the same conclusions of the authors. The role of palifermin in mucositis prevention, along with its safety profile, must be further elucidated in future trials.