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


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).


CONCLUSIONS
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.
Worden
Francis P
FP
Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan, Ann Arbor, MI, USA. fworden@umich.edu
Kumar
Bhavna
B
Lee
Julia S
JS
Wolf
Gregory T
GT
Cordell
Kitrina G
KG
Taylor
Jeremy M G
JM
Urba
Susan G
SG
Eisbruch
Avraham
A
Teknos
Theodoros N
TN
Chepeha
Douglas B
DB
Prince
Mark E
ME
Tsien
Christina I
CI
D'Silva
Nisha J
NJ
Yang
Kun
K
Kurnit
David M
DM
Mason
Heidi L
HL
Miller
Tamara H
TH
Wallace
Nancy E
NE
Bradford
Carol R
CR
Carey
Thomas E
TE
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery / Q000821:virology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery / Q000821:virology; D017239:Paclitaxel / Q000008:administration & dosage; D027383:Papillomaviridae / Q000302:isolation & purification; D018579:Patient Selection; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome
D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil