Worden Francis P, Kumar Bhavna, Lee Julia S, Wolf Gregory T, Cordell Kitrina G, Taylor Jeremy M G, Urba Susan G, Eisbruch Avraham, Teknos Theodoros N, Chepeha Douglas B, Prince Mark E, Tsien Christina I, D'Silva Nisha J, Yang Kun, Kurnit David M, Mason Heidi L, Miller Tamara H, Wallace Nancy E, Bradford Carol R, Carey Thomas E
Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan, Ann Arbor, MI, USA.
J Clin Oncol. 2008 Jul 1;26(19):3138-46. doi: 10.1200/JCO.2007.12.7597. Epub 2008 May 12.
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.
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.
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).
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.
测试诱导化疗（IC）后序贯同步放化疗（CRT）或手术/放疗（RT）用于治疗晚期口咽癌，并评估人乳头瘤病毒（HPV）对反应和结局的影响。
66例口咽鳞状细胞癌（SCCOP）Ⅲ至Ⅳ期患者（51例男性；15例女性）接受了一个周期的顺铂（100mg/m²）或卡铂（AUC 6）联合氟尿嘧啶（1000mg/m²/天，共5天）治疗，以筛选适合CRT的患者。那些原发肿瘤反应大于50%的患者接受CRT（70Gy；35次分割，同时每21天给予顺铂100mg/m²或卡铂（AUC 6），共三个周期）。对组织学完全缓解的患者给予辅助紫杉醇治疗。反应为50%或更低的患者接受根治性手术及术后放疗。对42例患者的治疗前活检标本进行了高危HPV检测。
66例患者中有54例（81%）在IC后反应大于50%。其中，53例（98%）接受了CRT，49例（92%）获得了组织学完全缓解，器官保留率为73.4%（64例中的47例）。4年总生存率（OS）为70.4%，疾病特异性生存率（DSS）为75.8%（中位随访时间，64.1个月）。42例活检标本中有27例（64.3%）检测到HPV16，其与较年轻的年龄（中位年龄，55岁对63岁；P = 0.016）、性别（30例男性中的22例[73.3%]和12例女性中的5例[41.7%]；P = 0.08）及不吸烟状态（P = 0.037）相关。HPV滴度与IC反应（P = 0.001）、CRT反应（P = 0.005）、OS（P = 0.007）和DSS（P = 0.008）显著相关。
尽管本研究中的病例数较少，但IC后序贯CRT是治疗SCCOP的一种有效方法，尤其是对于HPV阳性肿瘤患者；然而，对于治疗无反应的患者，必须开发替代治疗方法。
