TREATMENT WITH CISPLATIN AND FLUOROURACIL ALTERNATING WITH RADIATION FAVORABLY AFFECTS PROGNOSIS OF INOPERABLE SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK - RESULTS OF A MULTIVARIATE-ANALYSIS ON 273 PATIENTS

Purpose: The goal of the present analyses is to assess the association between different therapeutic approaches and both the probability of achieving a complete response and the risk of death in patients with s tage III-IV, inoperable, squamous cell carcinoma of the head and neck (SCC-HN). Patients and methods. Between August 1983 and December 1990, 273 patients with stage III-IV, previously untreated, unresectable SC C of the oral cavity, pharynx and larynx. were included into two conse cutive randomized multi-institutional trials (HN-7 and HN-8 protocols) coordinated by the National Institute for Cancer Research (NICR) of G enoa. The HN-7 protocol compared neo-adjuvant chemotherapy (four cycle s of vinblastine, 6 mg/m(2) i.v. followed by bleomycin, 30 IU i.m. six hours later, day 1; methotrexate, 200 mg i.v, day 2; leucovorin, 45 m g orally, day 3) (VBM) followed by standard radiotherapy (70-75 Gy in 7-8 weeks) (55 patients) to alternating chemoradiotherapy based on fou r cycles of the same chemotherapy alternated with three splits of radi ation, 20 Gy each (61 patients). In the HN-8 protocol standard radioth erapy (77 patients) was compared to the same alternating program as th e one used in the previous protocol but employing cisplatin, 20 mg/m(2 )/day and fluorouracil, 200 mg/m(2)/day, bolus, both given for five co nsecutive days (CF) instead of VBM (80 patients). A single database wa s created with the patients oil the two protocols. Age at diagnosis, g ender, site of the primary tumor, size of the primary, nodal involveme nt, performance status and treatment approach were analyzed by the mul tiple logistic regression model and the Cox regression method. The ana lyses were repeated including the treating institutions as a covariate (coordinating center versus others). Results: The multiple logistic r egression analysis indicates that treatment (alternating more so than others, regardless of the chemotherapy regimen used) (P = 0.0001) is m ore likely to be associated with complete response. In addition, size of the primary tumor (P = 0.004), nodal involvement (P = 0.02) and per formance status (P = 0.009) are prognostic variables affecting the pro bability of achieving a complete response. The Cox regression analysis indicates that treatment, performance status, size of the primary tum or, nodal involvement and, marginally, site of the primary tumor, are independent prognostic variables affecting the risk of death. When the radiation-alone therapy is adopted as the reference treatment, the re lative risk of death is 0.58 (95% confidence interval (CI) 0.40-0.84) for alternating CF and radiation, 0.79 (95% CI 0.53-1.16) for alternat ing VBM and radiation and 1.30 (95% CI 0.89-1.92) for sequential VBM a nd radiation. When the treating institution is included in the model, a 34% increased risk of death (P = 0.004) is observed for patients tre ated outside the coordi nating center. Conclusion. In our series of pa tients with advanced, unresectable SCC-HN, treatment with cisplatin an d fluorouracil alternating with radiation was associated with a more f avourable prognosis. The role of the treating institution in the modul ation of the treatment outcomes was also relevant.