Hyperfractionated radiotherapy: improvement of survival in locally advanced nasopharyngeal carcinoma.

OBJECTIVES: Standard treatment with concomitant chemotherapy (CT) and radiotherapy (RT) for nasopharyngeal cancer has shown rates of locoregional control of 80% and has improved the rate of 5-year survival to 67% to 84%. Hyperfractionated radiotherapy (HFRT) may increase locoregional control of tumors of the head and neck, but the addition of concomitant CT involves an unacceptable level of toxicity. Adding induction CT may control distant metastasis. Here we compare the results of our protocol with induction CT followed by HFRT alone with the results obtained with concomitant treatments. METHODS: Between October 1994 and May 2002, 46 patients with nasopharyngeal carcinoma were treated with HFRT. The patients with N+ or T4 lesions also received cisplatin-based induction CT (55%). RESULTS: The patients received a mean of 3 CT cycles (range, 2 to 5). At 5 years, the rate of progression-free survival was 66% (range, 51.3% to 82.1%), and the global survival rate was 75.7% (range, 61.9% to 89.5%). CONCLUSIONS: The use of HFRT in association with induction CT in patients with the greatest risk of metastasis may be as effective as concomitant CT-RT for treatment of nasopharyngeal cancer. Efforts should now concentrate on minimizing the acute and chronic toxicities.

Does induction chemotherapy still have a role in larynx preservation strategies? The experience of Institut Catala d'Oncologia in stage III larynx carcinoma.

BACKGROUND: Radiotherapy with concurrent cisplatin is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of induction chemotherapy in larynx-preservation therapies remains unknown. Hyperfractionation radiotherapy might improve disease-free survival. METHODS: From August 1993 to August 2004, 71 patients with T3N0-1 larynx tumors and eligible for total laryngectomy received induction chemotherapy with three cycles of cisplatin plus fluorouracil. Clinical tumor response was assessed by indirect laryngoscopy and computed tomography scan. Patients with complete response received hyperfractionation radiotherapy, whereas those without complete response were proposed for total laryngectomy. RESULTS: A total of 71 consecutive patients were included. Thirty-three patients achieved complete response to induction chemotherapy (46.5%), four of them presented a tumor relapse, and all underwent salvage surgery. Seventy-six percent of surviving patients preserved a functional larynx. Despite not achieving complete response, 15 patients refused total laryngectomy and received hyperfractionation radiotherapy. Seven patients presented a tumor relapse and salvage surgery was performed in three of them. Fifty percent of surviving patients preserved a functional larynx. Twenty-two patients without complete response underwent total laryngectomy; three of them presented a tumor relapse but none could be rescued. With a median follow up of 68 months, 5 five-year overall survival, 5-year disease-free survival, and 5-year larynx function preservation survival rates were 68% (confidence interval [CI], 57-80), 75% (CI, 64-87), and 42% (CI, 29-54), respectively. No differences in overall survival were observed between groups. Five-year disease-free survival of patients without complete response who received hyperfractionation radiotherapy was significantly lower than that of the other two groups (P < .02). Ten patients with larynx preservation and no tumor relapse had chronic toxicity that caused the loss of larynx function: seven patients required permanent tracheotomy, two died from pneumonia, and one patient died as a result of a laryngeal necrosis. CONCLUSIONS: Patients with complete response to induction chemotherapy in laryngeal carcinoma have a high probability of cure after hyperfractionation radiotherapy. However, hyperfractionation radiotherapy induces a high degree of toxicity that reduces the laryngeal function preservation rate and may jeopardize overall survival.

Twice-a-day radiotherapy for head and neck cancer: the Catalan Institute of Oncology experience.

PURPOSE: The purpose of this work is to evaluate the contribution of hyperfractionated radiotherapy (RT) in head and neck cancer by sub-localisation. PATIENTS AND METHODS: From 1992 to 1999, 318 patients with squamous head and neck tumours treated by hyperfraction RT were analysed according to their sub-localisation and stage. Fractions used were 1.2 Gy twice-a-day with a curative intent on all patients, to a total mean dose of 79.14 Gy. Treatment protocols by localisation were: larynx: 55 patients with T2N0 and T1-2N1 tumours treated with only RT and 27 patients with T3N0-1 in complete remission after three cycles of induction chemotherapy (ICT); hypopharynx: 29 patients with T2-4N0-2b resectable tumors in response to three cycles of ICT; oropharynx: 48 patients with T2-3N0-1 and T1N1 tumours treated with only RT; 34 patients with nasopharynx tumours treated with RT and three cycles of ICT if T4 or >N1; finally, 125 patients with non-surgical tumours of any localisation treated with four cycles of induction CT and RT. RESULTS: LARYNX: Actuarial local control (LC), disease-free survival (DFS) and overall survival (OS) at 5 years were 78, 73 and 48%, respectively, in T2 tumours and 75, 72 and 60% in stage III disease. HYPOPHARYNX: Actuarial LC, DFS and OS at 4 years were 44, 39 and 35%, respectively. OROPHARYNX: Actuarial LC, DFS and OS at 5 years were 52, 44 and 31%, respectively. NASOPHARYNX: Actuarial LC, DFS and OS at 5 years were 78, 72 and 78%, respectively. NON-SURGICAL TUMORS: Actuarial LC, DFS and OS at 5 years were 39, 33 and 19%, respectively. A total of 47 patients (14.8%) of the overall group had a second tumour, 72% of them tobacco-related. Only patients with nasopharynx tumours had a low incidence of second tumours. CONCLUSIONS: Twice-a-day external RT can be effectively managed in patients with head and neck cancer. Second neoplasm and intercurrent diseases become an important problem in low and medium stages whereas disease recurrences is the main problem in advanced stages. Results by localisation permit to obtain conclusions about their indications in each one.

Phase I/II docetaxel plus concurrent hyperfractionated radiotherapy in locally advanced unresectable head and neck cancer (TAX.ES1.102 study).

INTRODUCTION: Concurrent chemotherapy and radiotherapy is recommended for the treatment of locally advanced unresectable head and neck (H&N) cancer. OBJECTIVE: The primary purpose of the Phase I part of the study was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose (RD) of docetaxel with hyperfractionation radiotherapy. The primary objective of the Phase II part was to determine the response rate to the RD of treatment and, secondarily, to assess the toxicity of the schedule, time to progression, duration of response and overall survival (OS). MATERIALS AND METHODS: Patients (n=9 in Phase I; n=19 in Phase II) had unresectable H&N cancer. The starting docetaxel dose was 20 mg/m(2) plus hyperfractionated radiotherapy. Ramping of docetaxel was 5 mg/m(2) if MTD was not reached. RESULTS: MTD of docetaxel was 20 mg/m(2). Limiting toxicities were grade 4 pneumonia and grade 4 mucositis. The RD was 15 mg/m(2). Phase II initial response was 76% (CR=18%; PR=9%); updated response was 89% (CR=59%; PR=29%). The median progression-free survival was 7.8 months (95%CI: 0-22.3) and the median OS was 15.1 months (95%CI: 0-35.9). Grade 3-4 toxicities included mucositis (91%), pneumonia (27%) and fatigue (27%). There were 5 toxic deaths (2 from intestinal perforation, 3 from pneumonia). CONCLUSIONS: Weekly docetaxel+hyperfractionation radiotherapy is active but with high toxicity rates and, hence, this treatment regimen would be difficult to justify.