1. Carlson, Robert H.

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SAN ANTONIO-Reduced-intensity chemoradiotherapy appears to be as effective-and less toxic-than the current standard for patients with favorable-risk HPV-associated oropharyngeal squamous cell carcinoma, according to a prospective Phase II study reported here at the American Society for Radiation Oncology Annual Meeting (Abstract 3).

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In the study of 43 patients presented by Bhishamjit Chera, MD, Associate Professor of Radiation Oncology at the University of North Carolina School of Medicine, the dose of radiotherapy was reduced by 16 percent and the amount of chemotherapy was reduced by 60 percent.


The complete pathological response rate at 21 months was 86 percent, and residual disease was limited to microscopic foci.


But importantly, Chera said, patients had fewer side effects than those typically seen in patients who receive the standard dose, including having no lasting difficulty in swallowing.


Emerging data over the past decade show a rapidly increasing incidence of oropharyngeal cancer, and the possible cause or associated causal factor is human papilloma virus (HPV) infection, he continued. 'Some have called it an epidemic."


Standard treatment for patients with HPV-related squamous cell carcinoma of the oropharynx is a seven-week course of 70 Gy radiation in conjunction with cisplatin at a dose of 100 mg/m2) for three cycles.


In the study regimen, radiation therapy was reduced by 16 percent to a six-week course of 60 Gy, and the chemotherapy dose was reduced by 60 percent overall to 30 mg/m2 of cisplatin delivered concurrently for six weeks.


After patients completed chemoradiotherapy, the tumor site was biopsied and any lymph node regions that were originally cancer-positive were removed in order to determine the treatment's efficacy. All patients were alive with no evidence of disease at a median follow-up of 20.7 months. Of the 43 patients, 37 (86%) had a pathological complete response with no residual invasive tumor and no residual lymph node metastasis. The six patients with a partial response had residual disease limited to microscopic foci-one in the primary site and five in the nodes.


No Permanent Feeding Tubes

Chera noted that the adverse effects often associated with a standard chemoradiation regimen include chronic and acute difficulties in talking or swallowing, dry mouth, mucositis, tooth decay, and osteonecrosis.


Symptoms and quality of life were evaluated using two patient-reported questionnaires. Patients reported moderate to severe dry mouth immediately post-treatment, but at one year the patients were reporting that their dry mouth was only moderate.


Chera said that surprisingly, swallowing was not a problem for the patients in the study. Penetration aspiration scale scores for modified barium swallow studies were the same for patients eating thin, pureed, or solid foods before and after treatment.


Studies of standard chemoradiotherapy regimens have reported feeding tube rates of up to 80 percent, with approximately 10 percent of tubes having to be permanent, he noted. In contrast, in this study only 39 percent of patients needed a feeding tube, and none of them had to be permanent


"Our early findings suggest that less aggressive chemoradiotherapy resulted in less acute toxicity and a decrease in side effects of mucositis, nausea, vomiting, swallowing difficulty, and dryness of the mouth," Chera said.


New Way of Thinking

Deintensified treatment is "a whole new way of thinking about cancer care," said Benjamin Movsas, MD, Chairman of Radiation Oncology at Henry Ford Hospital in Detroit, who was the co-moderator of the session where the study was presented.


Asked afterward for his opinion, he said: "In general, the standard approach to cancer therapy is 'the more the better-let's throw more at the patient until we can't, and then we stop.' That's obviously the design of many trials that are looking for the maximum tolerated dose, and sometimes that is the approach we need.


"But now that we understand more of the underlying cancer biology, we know there are patients for whom the opposite is true and that we can actually de-intensify their therapy because they have a better biology, a better prognosis-they can do extremely well with less therapy."


Patients with HPV-associated squamous cell carcinoma of the oropharynx fit into that group, he continued. "The novel approach here is to get excellent tumor control but start enhancing quality of life and survivorship issues. Quality of life is so imperative because, at the end of the day only our patients can tell us how these treatments affect their daily lives, so it's important that we are incorporating these outcomes into our studies."


For many cancers, current standards of treatment are doing well in terms of tumor control and survival, "but now we need to ask how can we do better in terms of quality of life."


Phase III Trial?

The moderator of a news conference at the meeting on "novel clinical paradigms," that featured the study, Catherine Park, MD, Professor and Chair of the Department of Radiation Oncology at the University of California, San Francisco, also gave her perspective: "As we understand the biology of more favorable disease-this is also true in breast and other cancers-there is a strong interest in avoiding unnecessary treatment."


Still, the impact of this one study may not be practice changing, she said, as that usually takes data generated from a Phase III randomized trial. However, Park added, it might be difficult to mount a Phase III trial because knowledgeable patients would more likely want the deintensified protocol.