In what researchers from the University Hospital in Madrid, Spain, are calling a practice-changing study, sequential treatment with chemotherapy followed by chemoradiotherapy more than doubled time-to-treatment failure in patients with unresectable locally advanced head and neck cancer.
In what researchers from the University Hospital in Madrid, Spain, are calling a practice-changing study, sequential treatment with chemotherapy followed by chemoradiotherapy more than doubled time-to-treatment failure (TTF) in patients with unresectable locally advanced head and neck cancer. Ricardo Hitt, MD, PhD, led the phase III randomly controlled study.
From 2002-2007, Professor Hitt and associates assigned 439 patients with an ECOG performance status of 0-1 to receive standard radiochemotherapy with a cisplatin-based regimen alone (n = 128) or preceded by three cycles of induction chemotherapy with cisplatin and 5-fluorouracil (n = 156). Some patients in the sequential therapy arm also received docetaxel (n = 155). Patients were stratified according to location of the primary tumor; the majority (63%) had tumors of the oropharynx and oral cavity.
Researchers defined time-to-treatment failure as a “composite of time-to-disease progression, -to-surgery or other cancer-related treatments, -to-drop-out-due to an adverse event, and -to-death from any cause.” TTF in the sequential group was 12.5 months versus 5.0 months in the chemoradiotherapy cohort (P < .001; hazard ratio, 0.57; 95% confidence interval, 0.44-0.74), a statistically significant result. Locoregional control, a secondary endpoint of the study, was seen in 61.5% of patients who received induction chemotherapy followed by chemoradiotherapy and in 44.5% of patients who received chemoradiotherapy alone (P = .002). Researchers said that 438 patients were needed to produce a 15% difference in treatment failure, defined as death or disease progression or the need for surgery or other treatments.
More patients in the sequential therapy group experienced grade 3-4 adverse events than in the monotherapy arm (83% vs. 69%, respectively). The most common included febrile neutropenia, experienced by 10% of patients who received induction therapy prior to chemoradiotherapy compared with 1% in the chemoradiotherapy-alone arm; and stomatitis, which developed in 44% of patients on sequential therapy and 31% of those who did not receive induction chemotherapy (P = .002). “These study results illustrate that this complex disease deserves a rational and comprehensive management strategy to overcome its pathologic mechanism and the inherent possibility of failure and clinical control,” Professor Hitt said.
Fadlo Khuri, MD, professor and Roberto Goizueta Chair of Hematology and Medical Oncology at Emory University, Atlanta, Georgia, commented on the findings, saying, “These data may help define and clarify standard approaches to the treatment of patients with advanced unresectable disease.” The study is included in the Best of ASCO program.
ASCO Abstract #6009.