NEW YORK (Reuters Health) - Palifermin (Kepivance) helps reduce the rate, severity, and duration of severe oral mucositis in head and neck cancer patients receiving chemoradiotherapy, two new studies show.
"Combined data from both studies consistently indicated that palifermin has activities against radiochemotherapy-induced mucositis," said Dr. Quynh-Thu Le, who led one of the studies, in email to Reuters Health. "However, the lack of improvement in some of the secondary end points suggests that the doses and schedules tested were inadequate to overcome the severe mucositis brought on by concurrent radiochemotherapy."
The recombinant keratinocyte growth factor palifermin is FDA-approved to treat severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support.
But Dr. Le said that unlike the mucositis related to chemotherapy for bone marrow transplant, mucositis from chemoradiotherapy is more severe and persistent and "may require more drug administered at a higher frequency."
Dr. Le, from Stanford University, California, and colleagues tested palifermin, 180 mcg/kg IV once weekly, in 188 patients with locally advanced head and neck cancer receiving definitive chemoradiotherapy.
The incidence of severe oral mucositis (grade 3 or 4) was significantly lower with palifermin versus placebo (54% versus 69%; p = 0.041). In addition, the median duration of severe oral mucositis was shorter in the palifermin group (5 versus 26 days), according to a report published online June 13 in the Journal of Clinical Oncology.
But mouth and throat soreness (MTS) scores averaged only slightly lower in the palifermin arm, and that group had only an insignificantly lower median opioid analgesic dose.
Rash, flushing, dysgeusia, nausea, and vomiting were more common with palifermin.
In a parallel study published along with Dr. Le's, Dr. Michael Henke from University Clinic Freiburg, Germany, and colleagues tested a lower weekly dose -- 120 mcg/kg -- in 186 patients undergoing postoperative radiochemotherapy for locally advanced head and neck cancer.
The research team had started off with a dose of 180 mcg/kg but reduced it after one of the first 10 patients developed respiratory insufficiency.
The incidence of severe oral mucositis was significantly lower with palifermin versus placebo (51% versus 67%; p = 0.027), and the median duration was significantly shorter (4.5 versus 22.0 days; p = 0.037). Also, the onset of severe oral mucositis was delayed with palifermin (median 45 versus 32 days; p = 0.022).
Dysphagia, diarrhea, asthenia, headache, abdominal pain, and back pain were more commonly reported with palifermin, whereas dehydration, leukopenia, insomnia, fatigue, and mucosal inflammation were more often reported by placebo patients.
Progression-free survival did not differ between palifermin and placebo groups in either study.
"It is quite difficult to conduct trials in chemoradiotherapy-related mucositis for head and neck cancer due to several factors, including the underlying symptoms (mainly pain) related to the cancer, the heterogeneity of the patient population, and the differences in the patients' pain threshold," Dr. Le said. "This is a reason for all the negative studies to date. However, it's an important clinical problem to tackle and one should not give up on it."
Amgen sponsored both studies. Four Amgen employees were authors in the Henke study and five were authors in the Le study. Three additional authors in the Le study received research funding from Amgen. Palifermin is now marketed by Biovitrum AB.
By Will Boggs, MD
Sources: https://bit.ly/lZWxJC, https://bit.ly/jQKGZh
J Clin Oncol 2011.
Last Updated: 2011-06-13 18:30:12 -0400 (Reuters Health)
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