Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number

J Clin Oncol. 2008 Jul 1;26(19):3138-46. doi: 10.1200/JCO.2007.12.7597. Epub 2008 May 12.

Abstract

Purpose: To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome.

Patients and methods: Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m(2)) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m(2)/d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m(2) or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV.

Results: Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008).

Conclusion: Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Area Under Curve
  • Carboplatin / administration & dosage
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / surgery
  • Carcinoma, Squamous Cell / virology
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Oropharyngeal Neoplasms / drug therapy*
  • Oropharyngeal Neoplasms / radiotherapy
  • Oropharyngeal Neoplasms / surgery
  • Oropharyngeal Neoplasms / virology
  • Paclitaxel / administration & dosage
  • Papillomaviridae / isolation & purification
  • Patient Selection*
  • Proportional Hazards Models
  • Statistics, Nonparametric
  • Survival Rate
  • Treatment Outcome

Substances

  • Carboplatin
  • Paclitaxel
  • Cisplatin
  • Fluorouracil