A RANDOMIZED PHASE-II STUDY COMPARING SEQUENTIAL VERSUS SIMULTANEOUS CHEMORADIOTHERAPY IN PATIENTS WITH UNRESECTABLE LOCALLY ADVANCED SQUAMOUS-CELL CANCER OF THE HEAD AND NECK

Background: Single-modality radiotherapy is still considered standard treatment for patients with locally advanced unresectable cancer of th e head and neck. As treatment outcome is poor, attempts to integrate c hemotherapy into the overall management of these patients are ongoing. Patients and methods: A randomized study was undertaken to compare a sequential with a simultaneous chemo-radiotherapy program. Between Feb ruary 1986 and February 1991, 93 eligible patients with locally advanc ed unresectable cancer of the head and neck were stratified by WHO PS, T and N class and primary site and then randomized to receive either three courses of neoadjuvant chemotherapy with cisplatin (100 Mg/M2 i. v . d 1) and 5-fluorouracil 1000 mg/m2/days 1-5 by continuous i.v. inf usion every 3 weeks prior to definitive conventional radiotherapy of 6 5-70 Gy (sequential treatment), or cisplatin 100 mg/m2 on days 1, 22, 43 given simultaneously for the duration of the same conventional radi otherapy (simultaneous treatment). Results: At the end of the entire t reatment 18 complete responses (47%) in the sequential-treatment arm a nd 18 (41%) in the simultaneous treatment arm were obtained. No statis tically significant differences in the 5-yr progression-free survival, in the median time to loco-regional and distant progression and in th e 5-yr overall survival were observed. Leukopenia was more frequent in the simultaneous than in the sequential arm (p = 0.03), whereas alope cia (p = 0.008) and phlebitis (p < 0.0001) were more frequent in the s equential-treatment arm. A better compliance was associated with the c oncomitant treatment, with 87% of the patients completing the entire r adiotherapy program versus 63% of those in the sequential arm (p = 0.0 1). Conclusions: In the present study, the two treatment arms showed s imilar activity (complete response, progression-free and overall survi val rates). Compliance to treatment was better in the concomitant arm. These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the he ad and neck. Phase III studies are needed in order to establish the su periority of this combination of cisplatin and radiotherapy versus rad iotherapy alone.