Alternating gemcitabine and cisplatin with gemcitabine and radiation in stage IV squamous cell carcinoma of the head and neck.

BACKGROUND: In order to improve our cisplatin-5-fluorouracil (5-FU)-based alternating chemo-radiotherapy regimen, in 1996 we started an investigational program to explore a modified alternating regimen including gemcitabine given both with radiosensitizing and cytotoxic intent. MATERIALS AND METHODS: Based on our previous feasibility trial, we conducted a second study testing the feasibility and activity of the following schedule: gemcitabine 800 mg/m(2) on day 1 and cisplatin 20 mg/m(2) on days 2-5 (weeks 1, 4, 7 and 10) alternated with three courses of radiotherapy (RT) (weeks 2-3, 5-6 and 8-9) with conventional fractionation up to 60 Gy. Gemcitabine 300 mg/m(2) was also administered on the Monday of each week of RT. RESULTS: Forty-seven patients with stage IV (41 patients) unresectable squamous cell carcinoma of the head and neck (SCC-HN) or who had relapsed after surgery (6 patients) were enrolled. None had previously received chemotherapy or radiotherapy. Eight patients (18%) did not complete the treatment. Main grade 3-4 toxicities were as follows: neutropenia (44%); neutropenia with fever (12%); thrombocytopenia (37%); anemia (30% grade 3). One patient died in therapy due to sepsis. Most patients needed hospitalization and tube-feeding or parenteral nutrition. However, 44% of patients had a weight loss >10%. Thirty-four patients had a complete response (72%). Three partial responders were rendered disease-free by surgery (final complete response rate, 79%). At a median follow-up of 38 months actuarial 3-year overall survival, progression-free survival and loco-regional control are 43%, 39% and 64%, respectively. Data of locoregional control favorably compare with those from our database of patients treated with alternating cisplatin-fluorouracil and radiation within controlled clinical trials (64% versus 40%). CONCLUSIONS: The inclusion of gemcitabine into an alternating regimen seems to improve the results achievable with the original alternating program in stage IV patients. However, due to the high acute toxicity correlated, this intensive regimen should be managed by institutions well trained in multidisciplinary treatments.

Impact of the treating institution on the survival of patients with head and neck cancer treated with concomitant alternating chemotherapy and radiation.

The aim of this study was to investigate the possible impact of the treating institution on the survival of patients with advanced squamous cell carcinoma of the head and neck treated with radiotherapy alone or concomitant alternating chemotherapy and radiation. The National Institute for Cancer Research of Genoa (IST) was the coordinator of two multicentre randomised trials comparing an alternating chemotherapy and radiation approach to radiotherapy alone with standard fractionation (HN-8 trial: 157 patients) or accelerated fractionation (HN-9 trial: 136 patients) in patients with advanced squamous-cell carcinoma of the head and neck. A single database of the two studies was created and a univariate analysis was performed. The Cox regression model, adjusted for the effect of other prognostic factors, was used to test the impact of the treating institution on survival. Three-year overall survival was 46% for patients treated with chemotherapy and radiation at the coordinating centre and 27% for those treated with the same approach at the affiliated centres (P=0.0001). No difference was detected between patients treated with radiation alone at the coordinating centre or outside (23% versus 21%: P=0.52). The hazard ratio of death for patients treated at the affiliated centres with concomitant alternating chemotherapy and radiation was 2.15 (95% Confidence Interval (C.I.) 1.45-3.18), while it was 1.003 (95% C.I. 0.65-1.55) for those treated with radiation alone. In our experience, the treating institution had a significant impact only on the prognosis of patients treated with the multidisciplinary approach. This finding has implications, both in terms of clinical research and clinical practice.