June 30, 2011 — Palifermin (Kepivance), which is currently approved for preventing mucositis associated with total-body irradiation and stem-cell transplantation in hematologic malignancies, also prevents oral mucositis in patients with head and neck cancer undergoing radiation and chemotherapy, according to 2 randomized trials published online June 13 in the Journal of Clinical Oncology.
Michael Henke, MD, who led both studies, told Medscape Medical News that "this shows for the first time that radiation-induced mucositis can be ameliorated — and this in a phase 2/3 design!" Dr. Henke is from the Department of Radiation Oncology at University Clinic in Freiburg, Germany. The multicenter studies included researchers from Austria, France, Germany, Hungary, Italy, Poland, Spain, the United Kingdom, and the United States.
The first study was a double-blind randomized placebo-controlled trial of 186 patients with stage II to IVB carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Treatment included radiation, 60 or 66 Gy, after complete or incomplete resection, delivered at 2 Gy per fraction and 5 fractions per week. Treatment also included cisplatin 100 mg/m2 on days 1 and 22 (and on day 43 with incomplete resection).
Patients were randomized to weekly palifermin 120 μg/kg or placebo from 3 days before and throughout radiochemotherapy. The primary end point was the incidence of severe oral mucositis (World Health Organization [WHO] grades 3 to 4).
Palifermin reduced oral mucositis incidence to 51% (41 of 92), compared with 67% (63 of 94) with placebo (P = .027), shortened median mucositis from 22.0 to 4.5 days, and prolonged time to severe mucositis development from 32 to 45 days. Mortality was similar in both groups.
The authors conclude that "palifermin reduced the occurrence of severe oral mucositis in patients with head and neck cancer undergoing postoperative radiochemotherapy. Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful."
The second study randomized patients scheduled for definitive chemoradiotherapy for locally advanced head and neck cancer to either palifermin (180 μg/kg, n = 94) or placebo (n = 94) before starting chemoradiotherapy, and then once weekly for 7 weeks. Patients received conventionally fractionated radiotherapy (2.0 Gy per day for 5 days per week, to 70 Gy) with cisplatin (100 mg/m2 on days 1, 22, and 43). The primary end point was the incidence of severe oral mucositis (WHO grade 3 to 4).
Palifermin cut the incidence of severe oral mucositis from 69% to 54% (P = .041), delayed median time to severe oral mucositis from 35 to 47 days, and shortened the median duration of severe oral mucositis from 26 to 5 days.
Adverse events, overall survival, and progression-free survival were similar in the 2 treatment groups.
The researchers conclude that "although palifermin reduced severe functional [oral mucositis], its role in the management of locally advanced [head and neck cancer] during chemoradiotherapy remains to be elucidated."
Dr. Henke said that although several of the end points were not statistically significant after multiplicity adjustment, he thinks that they would have been significant with larger sample sizes.
"Given the proof-of-principle that mucositis is reduced by [palifermin], I am quite positive that its clinical relevance will be proven after adjustment of drug scheduling/dosing," Dr. Henke said.
He added: "Any means to reduce mucositis will be helpful. It's really debilitating and makes our patients suffer. One way to go will be smaller phase 2 work on when and at what dose to administer the drug to patients receiving radiation for head and neck cancer." He also suggested that palifermin might have value in novel radiation techniques sparing normal tissue.
The studies were supported by Amgen. Dr. Henke reports being in employment or leadership positions at Amgen and owning Amgen stock.
J Clin Oncol. Published online June 13, 2011. Abstract, Abstract
Michael Henke, MD, who led both studies, told Medscape Medical News that "this shows for the first time that radiation-induced mucositis can be ameliorated — and this in a phase 2/3 design!" Dr. Henke is from the Department of Radiation Oncology at University Clinic in Freiburg, Germany. The multicenter studies included researchers from Austria, France, Germany, Hungary, Italy, Poland, Spain, the United Kingdom, and the United States.
The first study was a double-blind randomized placebo-controlled trial of 186 patients with stage II to IVB carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Treatment included radiation, 60 or 66 Gy, after complete or incomplete resection, delivered at 2 Gy per fraction and 5 fractions per week. Treatment also included cisplatin 100 mg/m2 on days 1 and 22 (and on day 43 with incomplete resection).
Patients were randomized to weekly palifermin 120 μg/kg or placebo from 3 days before and throughout radiochemotherapy. The primary end point was the incidence of severe oral mucositis (World Health Organization [WHO] grades 3 to 4).
Palifermin reduced oral mucositis incidence to 51% (41 of 92), compared with 67% (63 of 94) with placebo (P = .027), shortened median mucositis from 22.0 to 4.5 days, and prolonged time to severe mucositis development from 32 to 45 days. Mortality was similar in both groups.
The authors conclude that "palifermin reduced the occurrence of severe oral mucositis in patients with head and neck cancer undergoing postoperative radiochemotherapy. Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful."
The second study randomized patients scheduled for definitive chemoradiotherapy for locally advanced head and neck cancer to either palifermin (180 μg/kg, n = 94) or placebo (n = 94) before starting chemoradiotherapy, and then once weekly for 7 weeks. Patients received conventionally fractionated radiotherapy (2.0 Gy per day for 5 days per week, to 70 Gy) with cisplatin (100 mg/m2 on days 1, 22, and 43). The primary end point was the incidence of severe oral mucositis (WHO grade 3 to 4).
Palifermin cut the incidence of severe oral mucositis from 69% to 54% (P = .041), delayed median time to severe oral mucositis from 35 to 47 days, and shortened the median duration of severe oral mucositis from 26 to 5 days.
Adverse events, overall survival, and progression-free survival were similar in the 2 treatment groups.
The researchers conclude that "although palifermin reduced severe functional [oral mucositis], its role in the management of locally advanced [head and neck cancer] during chemoradiotherapy remains to be elucidated."
Dr. Henke said that although several of the end points were not statistically significant after multiplicity adjustment, he thinks that they would have been significant with larger sample sizes.
"Given the proof-of-principle that mucositis is reduced by [palifermin], I am quite positive that its clinical relevance will be proven after adjustment of drug scheduling/dosing," Dr. Henke said.
He added: "Any means to reduce mucositis will be helpful. It's really debilitating and makes our patients suffer. One way to go will be smaller phase 2 work on when and at what dose to administer the drug to patients receiving radiation for head and neck cancer." He also suggested that palifermin might have value in novel radiation techniques sparing normal tissue.
The studies were supported by Amgen. Dr. Henke reports being in employment or leadership positions at Amgen and owning Amgen stock.
J Clin Oncol. Published online June 13, 2011. Abstract, Abstract
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