title: Pilot study of organ preservation multimodality therapy for locally advanced resectable oropharyngeal carcinoma.
abstract: The purpose of this study was to determine the early efficacy and toxicity of a new multimodality organ-preservation regimen for locally advanced, resectable oropharyngeal squamous cell carcinoma (SCC). Patients with T3-4N0-3M0 or T2N2-3M0 oropharyngeal SCC were eligible for this Phase II study. Patients needed the physiologic reserve for surgery and technically resectable tumors. Induction carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) x 2 cycles (q21 days) were given. Objective responders received definitive radiotherapy (XRT), 70 Gy/7 weeks with concurrent weekly paclitaxel. Initially, the dose of paclitaxel was 50 mg/m2/week; because of mucosal toxicity it was reduced to 30 mg/m2/week. Patients with N2-3 disease received post-XRT neck dissection and 2 more cycles of "adjuvant" chemotherapy. In the first 22 patients, the neutropenic fever rate was 27%. Although there has been no grade IV-V toxicity from induction therapy, grade II-III toxicity resulted in an unacceptable delay in starting XRT in 14% of patients. The response rate to induction chemotherapy was 91%. Grade III mucositis occurred in all patients during concurrent chemoradiotherapy. One patient died of pneumonia during concurrent chemoradiotherapy after receiving 26 Gy and 3 doses of paclitaxel 50 mg/m2. No dose-limiting toxicity occurred in 15 patients treated with concurrent paclitaxel 30 mg/m2/week. Actuarial overall survival at 18 months is 82%; local-regional control is 86%. To date, distant metastases have not developed in any patients. This regimen has intense but acceptable acute toxicity. The maximum tolerated dosage of weekly paclitaxel during standard continuous-course XRT is confirmed to be 30 mg/m2/week. The treatment efficacy of this regimen (response rate and short-term local-regional and distant control) is encouraging. Accrual continues to obtain long-term toxicity, efficacy, and quality-of-life data.
authors.affiliation: Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: M
authors.initials: M
authors.lastname: Machtay
authors.forename: D I
authors.initials: DI
authors.lastname: Rosenthal
authors.forename: K M
authors.initials: KM
authors.lastname: Algazy
authors.forename: V M
authors.initials: VM
authors.lastname: Aviles
authors.forename: A A
authors.initials: AA
authors.lastname: Chalian
authors.forename: D
authors.initials: D
authors.lastname: Hershock
authors.forename: R
authors.initials: R
authors.lastname: Neubauer
authors.forename: M J
authors.initials: MJ
authors.lastname: Greenberg
authors.forename: N
authors.initials: N
authors.lastname: Mirza
authors.forename: G S
authors.initials: GS
authors.lastname: Weinstein
authors.forename: R S
authors.initials: RS
authors.lastname: Weber
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D007825:Laryngectomy; D037981:Neck Dissection; D009959:Oropharyngeal Neoplasms / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D016019:Survival Analysis
chemical_list: D016190:Carboplatin; D017239:Paclitaxel