(CHICAGO, IL)—Although a significant decrease in rates of lower distant failure and high survival rates were observed with induction chemotherapy (IC) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN), these gains did not translate into improved overall survival (OS), according to a study presented at the 2012 American Society of Clinical Oncology Annual Meeting.
The goal of the open-label phase 3 DeCIDE trial was to determine whether induction chemotherapy prior to chemoradiotherapy (CRT) improves survival compared to CRT alone, according to lead author Ezra E. W. Cohen, MD, associate professor of medicine, the University of Chicago, Chicago, IL, and colleagues.
From 2004 to 2009, 280 patients with pathologically confirmed SCCHN, N2/N3 disease without metastases, no prior therapy, KPS 70%, and intact organ function were randomized to CRT alone (CRT arm), five days of docetaxel 25mg/m2, 5-FU 600mg/m2, hydroxyurea 500mg twice daily, and RT 150cGy twice daily followed by a nine-day break or to two cycles of induction chemotherapy, docetaxel 75mg/m2, cisplatin 75mg/m2, and 5-FU 750mg/m2 Days 1-5 followed by the same CRT (IC arm). Primary end point was overall survival (OS).
Minimum follow-up was 24 months. Of 142 patients randomized to IC, 91% received two cycles and 87% continued to CRT. “Treatment adherence during CRT was high for docetaxel and hydroxyurea, but fewer than 75% of the patients received target dose of 5-FU in both arms,” Dr. Cohen noted. RT was delivered without major deviations in 94% of patients on IC and 95% on CRT.
At 3 years, OS was 75% in the IC arm and 73% in the CRT arm (HR 0.91; P=0.68). Distant-failure free survival was 69% and 64% (HR 0.84; P=0.37); cumulative incidence of distant failure was 10% and 19% (HR 0.46; P=0.025), and cumulative incidence of locoregional failure was 9% and 12% (HR 0.79; P=0.55), respectively.
The most common grade 3 or 4 toxicities during IC were febrile neutropenia (9.6%) and clinical mucositis (12%); during CRT (both arms combined), functional mucositis (45%), dermatitis (20%), and leukopenia (18.2%) were observed. Only grade 3 or 4 leukopenia and neutropenia rates were significantly higher in IC (P=0.004 and P=0.02, respectively).
“In this study, induction chemotherapy did not improve survival, but improved cumulative incidence of distant failure,” Dr. Cohen concluded.