SAN ANTONIO – Patients who have low-risk, human papillomavirus (HPV)–associated oropharyngeal cancers may be effectively and safely treated with a reduced intensity chemoradiotherapy regimen, according to research presented at the annual meeting of the American Society for Radiation Oncology.
In the prospective, multi-institutional, phase II trial, complete pathologic responses (pCR) were seen in 86% of the 43 patients treated. The six cases that did not show a pCR were limited to microscopic areas of residual cancer.
ASTRO/Adam Donohue
Dr. Bhishamjit Chera
The study provides strong preliminary evidence that reduced intensity chemoradiotherapy may be as effective as standard-dose chemoradiotherapy, Dr. Bhishamjit Chera of the University of North Carolina at Chapel Hill said at a press briefing. While it is too early to use outside of a clinical trial at present, he said, there is the potential for less intensive treatment to be given, and it could be the standard practice in years to come.
“At most institutions, the standard treatment for oropharynx cancer is definite chemoradiation,” Dr. Chera explained. This typically involves delivery of 70 Gy of radiation, given in 2-Gy fractions over 7 weeks for a total 35 days of treatment, and administration of three doses of cisplatin 100 mg/m2 concurrently.
“This treatment provides the best chances of sparing the tonsil, the throat, and the tongue, basically preserving organ function,” he added. Surgery is not usually performed unless there are signs on imaging that the cancer has not completely resolved 12 weeks after treatment.
“We know that many patients are cured with oropharyngeal carcinoma, but many patients live with significant long-term side effects such as dry mouth and difficulty swallowing,” Dr. Chera observed. Thus the aim of the present trial was to see if reducing the intensity of the chemoradiotherapy might avoid some of the side effects seen.
The deintensified regimen used in the study consisted of a 10-Gy reduction in the total dose of radiation delivered to 60 Gy, which was given in 2-Gy fractions once daily over a period of 6 weeks. The dose of cisplatin also was reduced by approximately 40% to 30 mg/m2 given in 6 weekly doses
Patients were eligible for inclusion if they had stage 0-3 squamous cell carcinoma of the oropharynx, with limited nodal (N0-N2c) and no metastatic involvement. Patients had to have a minimal smoking history and be HPV or p16 positive.
After the chemoradiation, all patients underwent a planned biopsy and limited neck dissection to remove any lymph nodes that had cancer in them prior to treatment. Thus the primary endpoint was the pCR rather a radiographically measured tumor response rate, Dr. Chera observed.
Considering just the primary site of the cancer (the base of tongue and tonsil), there were 41 patients who could be evaluated and all but one of these (98%) achieved a pCR. Looking at patients with neck involvement at baseline (n = 39), 84% achieved a pCR.
“All of these 43 patients are alive with no evidence of cancer recurrence with a follow-up of 21 months,” Dr. Chera reported.
Throughout the study, patient-reported outcomes were captured using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the European Organization for Cancer Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ).
While patients did report an increase in adverse effects 6-8 weeks after the chemoradiation, the intensity of these side effects decreased to baseline levels over time. Not surprisingly, the two most common symptoms were dry mouth and problems with swallowing, with 75% and 55% of patients, respectively, experiencing severe or very severe xerostomia and dysphagia. Other grade 3-4 adverse events included mucositis in 45%, pain in 48%, nausea in 52%, and vomiting in 34%.
Results of the quality of life analyses show that patients’ quality of life is returning to baseline levels after 1 year.
“There is a lot of interest in reducing the intensity of treatment in these patients,” Dr. Chera said, adding that patients are likely being overtreated at present. In the current clinical environment, patients are very savvy, he said, so performing a large randomized phase III trial may not be possible if patients learn that deintensified therapy may be an option. So the results of larger and longer phase II trials may be the best evidence that will be obtained.
The NRG Oncology group is going to evaluate the same deintensified chemotherapy regimen in another, larger phase II trial, the NRG-HN002 trial, Dr. Chera said. This trial aims to accrue almost 300 patients and will compare the University of North Carolina regimen versus radiation alone, which will be given at a total dose of 50 Gy 5 days a week for 5 weeks.