Rapidly alternating chemotherapy and radiotherapy in advanced laryngeal cancers.

Abstract

e16032 Background: Rapidly alternating chemotherapy and radiotherapy (ACR) is a minor variation of concurrent chemoradiation (CCR). This scheduling and 5-fluorouracil (5-FU) pretreatment followed by cisplatin (FP) treatment have been tested in advanced laryngeal cancers. ACR allows the simultaneous administration of both treatment modalities without increasing toxicity, while pretreatment with 5-FU induces long arrest in S-phase, and enhances cisplatin cytotoxicity (Cancer Chemother Pharmacol, 2008). We conducted a phase II clinical trial to evaluate these hypotheses. Methods: Eligibility: histologically proven squamous cell carcinoma of larynx with stage III or IV, PS 0-1, age <= 75, adequate organ functions, and no prior chemotherapy. Chemotherapy consisted of administration of continuous infusion of 5-FU at 700 mg/m2/day on days 1-5, and 2-hour infusions of cisplatin at 80 mg/m2/day on day 6 (1st week). Once-daily radiotherapy of 36 Gy in 18 fractions was given starting on day 8 (2nd -5th week). Sequentially, FP treatment was repeated twice (6th week) for responders, and radiotherapy of 30 Gy in 15 fractions was given (7-9th week) in total 66 Gy. Results: From 4/2007 to 11/2010, 27 patients (pts) were enrolled. Patient characteristics were median age of 67 (49-74) years; gender, 26 male and 1 female; subsite, glottis 16 pts (59%) and supraglottis 11 (41%); stage, III 15 pts (56%), IV 12 (44%). 23 responders (85%) completed radiotherapy, and of them 20 pts (87%) received two courses of chemotherapy. 20 primary sites (74%) achieved CR by ACR. 4 non-responders (15%) underwent early salvage surgery. 7 pts had salvage surgery and neck dissection. Toxicity was assessed in all pts: 12 grade 3 events (44%; nausea 7, mucositis 4 (15%) and dermatitis 1). There have been no hematological grade 3 or 4 toxicities. The 3-year overall survival and laryngeal preservation rate were 88% and 65%, respectively. Conclusions: In this ACR trial, the rate of mucosal toxicity was equivalent to or less than those with radiotherapy alone, and the laryngeal preservation was equivalent to CCR in spite of 60% glottic carcinomas.