乌鸦传媒

A dual strategy of deintensified treatment for human papillomavirus (HPV)-positive oropharyngeal cancer led to 2-year locoregional control and overall survival (OS) of 95%, results of a prospective study showed.

Progression-free survival (PFS) at 2 years was 86%, and 91% of the 114 patients remained free of distant metastases. No grade ≥3 late adverse events occurred, and global quality of life improved from pretreatment to 2 years.

Incorporating a lower dose of cisplatin and lower total radiation dose, the protocol achieved encouraging results without neoadjuvant chemotherapy or routine surgery, Bhishamjit S. Chera, MD, of the University of North Carolina (UNC) at Chapel Hill, and coauthors reported in the .

"The data reported herein support the approach of deintensified CRT (chemoradiotherapy) without the need of neoadjuvant chemotherapy," the authors stated. "Future studies of the neoadjuvant chemotherapy and transoral surgery approach should attempt more radical reduction in RT dose to further reduce toxicity and improve QoL (quality of life)."

The study added valuable information to ongoing discussion and clinical evaluation of strategies to use less aggressive treatment for HPV-positive oropharyngeal cancer, which has a more favorable prognosis, as compared with HPV-negative disease, commented Paul M. Harari, MD, of the University of Wisconsin in Madison. The "excellent clinical outcomes," including survival and quality of life, extended an ongoing clinical collaboration between UNC and the University of Florida, evaluating reduced-dose radiation therapy protocols.

"We are learning that radiation dose reduction appears to be a highly worthy strategy to pursue in favorable HPV-positive head and neck cancer patients," Harari told 乌鸦传媒 via email. "Ultimately, however, phase III randomized data will be critical to establish concrete recommendations for this high-cure-rate population of cancer patients."

More data on the topic will emerge from the phase II collaborative group clinical trial, evaluating reduced-dose intensity modulated-radiotherapy (IMRT) with or without chemotherapy, he added. Initial results will be reported next month at the American Society for Radiation Oncology (ASTRO) meeting.

Conventional CRT protocols for HPV-positive oropharyngeal have led to excellent cancer control and survival but at a price of substantial toxicity. Over the past decade, investigators in numerous studies have examined various approaches to reduce toxicity without sacrificing disease control. The authors cited three common approaches to deintensify treatment:

• Reduce the radiation dose and increase the chemotherapy dose (including the addition of neoadjuvant therapy)
• Decrease the radiation dose and add transoral surgery
• Substitute cetuximab (Erbitux) for cisplatin

Several strategies were on display last year at professional meetings. Two studies reported at ASTRO suggested that lowering the radiation dose improved quality of life and might also reduce the cost of care. Two other studies, one reported at ASTRO and one at the European Society for Medical Oncology, showed that substituting cetuximab for cisplatin led to worse outcomes, including survival.

In 2011, Chera and colleagues began evaluating strategies to reduce both the radiation and the chemotherapy for patients with HPV-positive oropharyngeal cancer. Standard protocols consisted of weekly cisplatin at a dose of 40 mg/m² administered concurrently with a radiotherapy total dose of 70 Gy. The deintensified regimen consisted of cisplatin 30 mg/m² for 6 weeks plus a radiotherapy dose of 60 Gy. The protocol was evaluated in a phase II trial that had a primary endpoint of pathologic complete response.

"In 2011 the concept of deintensification was so new that we designed our protocol with a pathologic endpoint so that we would know as quickly as possible if tumor control was being compromised," the authors said of the trial.

The study demonstrated a pCR rate of 86% and 3-year PFS and overall survival OS of 100%. A second phase II trial was planned to verify that a mandated biopsy and selective neck dissection could be omitted safely.

Eligible patients had untreated, pathologically confirmed HPV p16-positive squamous cell carcinoma of the oropharynx or from an unknown primary site in the head and neck. The patients had T0-3 N0-2 M0 disease, ≤10 pack-year smoking history or abstinence for at least 5 years, and good performance status.

All patients received IMRT to a total dose of 60 Gy in 30 fractions over 6 weeks. The mandated first choice chemotherapy was cisplatin 30 mg/m² once a week, but exceptions were allowed for alternative weekly regimens (cetuximab, carboplatin/paclitaxel, carboplatin alone).

The primary endpoint was 2-year PFS. As a frame of reference, of standard CRT regimens resulted in 3- and 5-year PFS of 74% and 78%, respectively.

After a median follow-up of 31.5 months, the efficacy outcomes compared favorably with those of the prior trials of standard therapy. Assessment of QoL by the European Organization for Research and Treatment of Cancer instrument showed improvement in the mean score from 74 at baseline to 84 at 2 years. Swallowing score was similar at both assessments. Dry mouth was the most common treatment related adverse effect and worsened over time from a mean score of 14 at baseline to 45 at 2 years.

Patient-reported outcomes were consistent with the objective assessments. A third of patients required a feeding tube for a median duration of 10.5 weeks.

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