1. Goodwin, Peter

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CHICAGO-Patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinomas may be treated safely with doses of radiotherapy than are lower than the current standard of 70 Gy. That is the conclusion of the Phase II ECOG 1308 study reported here at the American Society of Clinical Oncology Annual Meeting (Abstract LBA6006).

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The rates of freedom from disease progression and overall survival were equivalent to those with standard therapy in patients treated with only 54 Gy in total.


Lead study author Anthony J. Cmelak, MD, Professor of Radiation Oncology at Vanderbilt-Ingram Cancer Center, said that although lowering the radiation dose did not compromise outcome in this study, longer follow-up is still needed, as well as confirmatory Phase III data, before reducing radiation doses in daily practice can be recommended.


"This potentially allows a significant-23 percent-reduction in overall radiation dose and a corresponding decrease in long-term toxicities associated with that," he said in an interview, describing the approach as a potential "new paradigm" in this select group of patients.


He and his co-researchers chose patients with good functional status who had resectable HPV-related cancers; patients were generally younger, and there were about 50 percent who were smokers and 50 percent who were non-smokers. Patients who achieved complete remissions after three cycles of cisplatin, paclitaxel, and cetuximab went on to receive reduced-dose radiation using intensity-modulated radiation therapy (IMRT) together with weekly cetuximab.


Among the 62 patients who did so, the progression-free survival rate at two years was 80 percent, and overall survival was 95 percent.


Toxicity was very mild, he noted: "There were very few grade 4 toxicities, and only one patient had one grade 3 toxicity in the long term-low magnesium at 30 months."


Up until now, he noted, oncologists have been satisfied to have achieved cures for head and neck cancers by "pushing chemotherapy and radiation, "but this has been at the expense of life-long toxicities such as stroke, swallowing dysfunction, loss of taste, dry mouth, dental problems, chronic fatigue, and hypothyroidism.


A previous study-ECOG 2399- had already found that patients with HPV-related oropharyngeal cancers had better progression-free survival times when treated with standard induction chemotherapy and radiation. So the ECOG 1308 study went on to test the hypothesis that cure rates could be maintained in these younger, healthier, non- or light-smoking patients to avoid a future burden of toxicity that they could have to endure perhaps for 30 or 40 years.


Non-smokers had the best outcomes, and in those who had non-bulky tumors-less than T4 and no contralateral lymph node involvement-both two-year progression-free and overall survival rates were 96 percent.


Still, since historically these patients have had recurrences at three, four, or five years out, he said, "we need longer-term follow-up and we also need to determine whether this is safe for all patients. We need to test what the best combination is so we don't jeopardize their chance for cure as well."


Speaking at an ASCO news conference highlighting studies showing improved patient care and quality of life, he said did not recommend using lower doses of radiation outside of clinical trials, and neither did the designated ASCO expert, Gregory A. Masters, MD, Director of the Medical Oncology Fellowship Program at Christiana Care Health System's Helen F Graham Cancer Center in Delaware.


In an interview, Masters said he welcomed the fact that tumor biology is now guiding precise therapies for individual patients. But he warned that this is still in the research phase and that the ECOG 1308 trial studied a particular group of patients only: those with oropharyngeal cancers selected for HPV positivity-not all head and neck cancers in general: "This was a Phase II trial, so I'm not ready to say that this is a standard of care for any patient: but it certainly is ready to be studied in a randomized trial in this group of patients," he said.

ANTHONY J. CMELAK, M... - Click to enlarge in new windowANTHONY J. CMELAK, MD. ANTHONY J. CMELAK, MD: "This was a Phase II trial, so I'm not ready to say that this is a standard of care for any patient, but it certainly is ready to be studied in a randomized trial in this group of patients."