Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma

Int J Radiat Oncol Biol Phys. 2015 Dec 1;93(5):976-85. doi: 10.1016/j.ijrobp.2015.08.033. Epub 2015 Aug 22.

Abstract

Purpose: To perform a prospective, multi-institutional, phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus-associated oropharyngeal squamous cell carcinoma.

Methods and materials: The major inclusion criteria were: (1) T0 to T3, N0 to N2c, M0; (2) human papillomavirus or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatinum (30 mg/m(2)). The primary study endpoint was pathologic complete response (pCR) rate based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless of radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and n=40, resulting in a type 1 error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Toxicity Terminology for Adverse Events, CTCAE), patient-reported symptoms (PRO-CTCAE), and modified barium swallow studies.

Results: The study population was 43 patients. The pCR rate was 86% (37 of 43). The incidence of CTCAE grade 3/4 toxicity and PRO-CTCAE severe/very severe symptoms was as follows: mucositis 34%/45%, general pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematologic toxicities were 11%. Thirty-nine percent of patients required a feeding tube for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in modified barium swallow studies before and after CRT.

Conclusions: The pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk oropharyngeal squamous cell carcinoma, with evidence of decreased toxicity compared with standard therapies. ClinicalTrials.gov ID: NCT01530997.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Biopsy
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Carcinoma, Squamous Cell / virology
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Cisplatin / administration & dosage
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Humans
  • Lymph Node Excision
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Oropharyngeal Neoplasms / chemistry
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / therapy*
  • Oropharyngeal Neoplasms / virology
  • Papillomaviridae
  • Papillomavirus Infections / complications*
  • Patient Compliance
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Radiotherapy, Intensity-Modulated / methods*
  • Smoking / epidemiology
  • Stomatitis / etiology
  • Stomatitis / pathology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • Cisplatin

Associated data

  • ClinicalTrials.gov/NCT01530997