Randomized phase II study of palifermin for reducing dysphagia in patients receiving concurrent chemoradiotherapy for locally advanced unresectable non-small cell lung cancer.
BACKGROUND
Dysphagia is a common, dose-limiting toxicity of combined chemoradiotherapy (CT/RT) in patients with locally advanced non-small cell lung cancer (NSCLC). This study assessed the efficacy and safety of palifermin in reducing dysphagia from CT/RT followed by consolidation chemotherapy (CT).


METHODS
This randomized, double-blind, phase II trial enrolled adults with unresectable stage III NSCLC. Subjects received weekly paclitaxel (50 mg/m2) and carboplatin (AUC 2.0) with concurrent daily radiation (RT) of 6000 to 6600 cGy, followed by consolidation CT. Palifermin (n = 49) or placebo (n = 46) was administered before starting concurrent CT/RT and once weekly for 6 weeks. The primary end points were the incidence of grade ≥ 2 dysphagia and safety.


RESULTS
The incidence of grade ≥ 2 and ≥ 3 dysphagia was numerically lower in palifermin subjects versus placebo subjects (61% versus 70%; p = 0.36; 22% versus 28%, p = 0.50, respectively). Mean duration of dysphagia (grade ≥ 2) was 25 days for palifermin subjects and 32 days for placebo subjects (p = 0.32). The incidence of adverse events was similar in the two treatment groups, and median overall survival and progression-free survival were not adversely affected by palifermin treatment (overall survival: 513 versus 319 days; progression-free survival: 262 versus 235 days for palifermin versus placebo arms, respectively). The palifermin arm received more doses of CT per study design and significantly more patients received RT doses ≥ 6000 cGy (84% versus 61%, p = 0.01).


CONCLUSIONS
The results of this exploratory trial suggest that additional larger studies may be warranted to further evaluate the effect of palifermin on dysphagia, exposure to CT/RT, and long-term survival.
Krankenhaus Martha-Maria Halle-Doelau, Klinik Innere Medizin II, Halle/Saale, Germany. Wolfgang.Schuette@Martha-Maria.de
Wolfgang
W
Schuette
Maciej J
MJ
Krzakowski
Bartomeu
B
Massuti
Gregory A
GA
Otterson
Richard
R
Lizambri
Helen
H
Wei
Dietmar P
DP
Berger
Yuhchyau
Y
Chen
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D003680:Deglutition Disorders / Q000188:drug therapy* / Q000209:etiology; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012720:Severity of Illness Index; D016896:Treatment Outcome
D051523:Fibroblast Growth Factor 7; D016190:Carboplatin; D017239:Paclitaxel