Κυριακή, 28 Φεβρουαρίου 2016

NO CLEAR BENEFIT OF INDUCTION CHEMOTHERAPY IN HEAD-NECK CANCER

Head and neck cancer patients who receive induction chemotherapy rather than the standard treatment of concurrent chemoradiation do not benefit from increased survival rates and are less likely to receive a full course of radiation, according to research presented by Stokes et al at the 2016 Multidisciplinary Head and Neck Cancer Symposium (Abstract 109). The study, which examined more than 8,000 patient records in the National Cancer Data Base, represents the largest comparative analysis of induction chemotherapy and concurrent chemoradiation in head and neck cancer to date.
The role of induction chemotherapy remains controversial in locally advanced head and neck squamous cell carcinoma. “Most randomized trials designed to address whether induction chemotherapy improves outcomes by enhancing local control and minimizing distant metastases have failed to demonstrate an increased overall survival benefit,” explained study co-author Daniel W. Bowles, MD, Assistant Professor in the Department of Medical Oncology at the University of Colorado School of Medicine and Director of Cancer Research and Staff Physician at the Denver VA Medical Center. “Those findings, however, typically were based on study designs that enrolled too few patients or too few patients with advanced cancers, thereby diluting the possible benefit of induction chemotherapy.”
Study Background
Dr. Bowles and colleagues extended the question of whether induction chemotherapy improves survival in head and neck squamous cell carcinoma to the 8,003 records in the National Cancer Data Base of patients diagnosed with T(any) N2b-3 M0 oropharyngeal, laryngeal, and hypopharyngeal cancers between 2003 and 2011.
Cases were classified into two cohorts based on the type of treatment delivered. Patients in the induction chemotherapy group (n = 1,917) began chemotherapy 43 to 98 days before starting radiation therapy; this time frame allowed for two to three cycles of induction chemotherapy, which is the common protocol in recent clinical trials. Patients in the concurrent chemoradiation group (n = 6,086) began chemotherapy within 7 days of radiation therapy start and did not receive induction chemotherapy. Of the two groups, the induction chemotherapy cohort tended to be younger and presented with more advanced disease, as well as more hypopharyngeal cancer.
Study Findings
Patients in the induction chemotherapy group were less likely to receive a full course of radiation therapy following administration of induction therapy. Twenty-one percent of the induction chemotherapy patients received less-than-definitive doses of radiation therapy (ie, < 66 Gy), compared to 15% of the concurrent chemoradiation patients (P < .01). Multivariate analyses adjusting for age, sex, race, income, location, year, comorbidities, primary disease site, T status, and N status confirmed the increased odds among the induction cohort of receiving non-guideline­–concordant radiation therapy doses (odds ratio [OR] = 1.42; P < .01).
Comparative analysis using Cox regression also indicated shorter median survival following induction chemotherapy compared to concurrent chemoradiation, with a median overall survival of 52 months for induction chemotherapy patients compared to 65 months for concurrent chemoradiation patients (P < .01), though this difference did not persist on multivariate (hazard ratio [HR] for mortality = 1.04; P = .28) or propensity score matched analysis (= .18).
Subgroup analyses further divided the treatment cohorts by disease stage to assess possible benefits of induction chemotherapy for advanced cases of head and neck squamous cell carcinoma. Induction chemotherapy did not improve overall survival even for patients with the most advanced disease, including T4 or N3 status (HR = 0.99; = .81), N3 status (HR = 0.98; P = .84), and T4N3 status (HR = 0.91; P = .53).


“While we suspected that induction chemotherapy would not have an impact on our entire study population, we thought it might prolong survival for the most advanced cancers,” said Dr. Bowles. “Our finding from this large database that induction chemotherapy is not associated with improved overall survival over concurrent chemoradiation, even for these patients, will continue to dampen enthusiasm for routine use of induction therapy. In cancer care, sometimes more is less. If adding induction chemotherapy fails to improve survival over the current standard of care, then we should reconsider its use.”

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