CONCOMITANT INFUSION CISPLATIN AND HYPERFRACTIONATED RADIOTHERAPY FORLOCALLY ADVANCED NASOPHARYNGEAL AND PARANASAL SINUS TUMORS

Purpose: This is a prospective study to improve the therapeutic ratio in the treatment of patients with locally advanced nasopharyngeal and paranasal sinus tumors by using split-course concomitant infusion cisp latin chemotherapy and hyperfractionated radiotherapy. Methods and Mat erials: From 1983 to 1993, 21 patients with locally advanced nasophary ngeal and paranasal sinus tumors (T3 and T4, or recurrent tumors invol ving the facial bones and/or the base of the skull) were treated with a regimen of split-course hyperfractioned radiotherapy (1.2 Gy/fractio n/bid) and concomitant infusion cisplatin (5-10 mg/m(2)/24 h), The the rapy was given in three separate 2-week sessions with 1 to 2 week brea ks between sessions, Seventeen of 21 patients were treated with curati ve intent with cumulative radiation doses ranging from 64.8 to 70.8 Gy , Four patients were treated with palliative intent to a total dose of less than 60 Gy or to a limited field due to previous irradiation. Re sults: Sixteen of 17 patients (94%) treated curatively achieved a comp lete response, Of the 16 patients who achieved complete response, 7 pa tients (50%) were alive at the time of analysis (36 to 126 months), On e patient was alive at 4 years with no evidence of disease, and died i n 10 years at the age of 80 of unknown cause, Two patients died of loc al recurrence at 21 and 45 months and one patient died of a cerebrovas cular accident at 12 months with disease status unknown, Five patients died of distant metastases. The one patient who had a partial respons e died in 25 months with local disease and metastases to the bone and lung, Four patients that were previously irradiated received a reduced total dose or treated to a limited irradiation field, All had near co mplete responses, but died within a year of treatment, with the except ion of one patient who died at 23 months, Acute reactions included int ense erythema of the mucosa in all patients, Five of 21 (23%) develope d punctate mucositis and 3 of 21 (14%) developed confluent mucositis, Hematologically, one patient developed neutropenia (1800 WBC/mm(3)) an d one developed thrombocytopenia (38,000/mm(3)), A rising creatinine w as observed in three patients (2.0, 1.7, 1.7) all of whom were treated with the higher 10 mg/m(2)/day dose of infusional cisplatin, In all t hree of these cases, the creatinine slowly returned to normal over a 6 -month period, Hormonal evaluations were performed in three patients a nd all were within normal ranges, There was no evidence of neck fibros is or trismus. One patient with gross recurrent disease of the orbit d eveloped blindness of the involved eye due to corneal opacification. T he orbital area had been reirradiated in this patient. Conclusions: Co ncomitant infusion cisplatinum with hyperfractionated radiation improv ed tumor control, but did not increase normal tissue injury, Acute rea ctions were minimized by splitting the treatment with a 1- to 2-week b reak after each 2 weeks of radiation treatment, Late complications wer e not increased by using a hyperfractionated radiation regimen, The lo cal failure rate was only 18% (3 of 17 patients), but the distant fail ure rate was 35% (6 patients), Further investigation is needed to prov e if adjuvant chemotherapy after concomitant chemoradiation improves s urvival by decreasing the distant failure in such advanced cases. (C) 1997 Elsevier Science Inc.