Chemotherapy Plus Radiotherapy Superior to Radiotherapy Alone for Some Inoperable Head and Neck Cancers

June 1, 1996

Further follow-up of a randomized trial comparing combined chemotherapy and radiotherapy with radiotherapy alone for inoperable squamous cell cancers of the head and neck confirms the trial's initial finding of greater efficacy for the combined

Further follow-up of a randomized trial comparing combined chemotherapyand radiotherapy with radiotherapy alone for inoperable squamouscell cancers of the head and neck confirms the trial's initialfinding of greater efficacy for the combined treatment. The newanalysis, performed after 5 years of follow-up, is reported inthe Journal of the National Cancer Institute.

Marco Merlano, MD, and colleagues at the National Institute forCancer Research, Genoa, Italy, followed 157 patients with untreatedunresectable squamous cell head and neck cancers who were randomlyassigned to receive either chemotherapy (four courses of cisplatin[Platinol] and fluorouracil given daily for 5 consecutive daysduring weeks 1, 4, 7, and 10) alternating with radiotherapy (threecourses of 20 Gy each, given in fractions of 2 Gy/d during weeks2-3, 5-6, and 8-9) or radiotherapy alone (70 Gy total, given infractions of 2 Gy/d 5 days per week) At total of 80 patients receivedthe combined therapy, and 77 received radiotherapy alone.

After 5 years, although the frequency of overall response to treatmentwas similar between the treatment groups, the group receivingcombined therapy showed a statistically significant increase inthe number of complete responses (ie, disappearance of clinicallydetectable disease for at least 4 weeks). Including patients inboth groups who were able to undergo surgery and become diseasefree following treatment, the complete response rate in the combined-therapygroup reached 53%, as compared with 26% for the radiotherapy-onlygroup.

The combined-therapy group also showed statistically significantincreases, compared with the radiotherapy-only group, in locoregionaldisease control (64% vs 32% after 5 years), progression-free survival(21% vs 9% after 5 years), and overall survival (24% vs 10% at5 years). Patients in the combined-treatment group, however, experienceda greater number of second primary tumors--a finding that theauthors believe is explained by their longer survival. Importantly,the incidence and severity of treatment-related toxic effects,particularly mouth ulcers (mucositis), were similar in the twotreatment groups; the authors conclude that the alternating, ratherthan simultaneous, chemotherapy and radiotherapy helped avoidthe expected additive toxicity in the combined-therapy group.

Study Limitations

The authors note that the findings must be considered with caution,since early termination of patient accrual to the study limitedits statistical power. A total of 180 patient entries to the studyhad been planned originally, but enrollment was stopped after157 patients because of the substantially higher complete responserate in the combined-therapy group.

Nonetheless, say Merlano and coworkers, the results confirm thesuperiority of an alternating regimen of chemotherapy and radiotherapyover radiotherapy alone in this series of patients. They concludethat improved local control of disease may underlie the observedimprovements in progression-free and overall survival. But, theysay, additional confirmatory trials must be conducted before thecombined approach can be considered standard therapy for advanced,unresectable squamous cell carcinoma of the head and neck. Theyalso believe that combined therapy may have implications for themanagement of earlier-stage disease, where it may prove to bea beneficial postoperative therapy or may enable organ preservation.

In an editorial accompanying the report, Bonnie S. Glisson, MD,and Waun Ki Hong, MD, of The University of Texas M.D. AndersonCancer Center, Houston, underscore the possible study limitationsoutlined by Merlano and coworkers and concur that the combined-therapyapproach cannot yet be recommended as standard therapy. Still,say Glisson and Hong, chemotherapy in conjunction with radiotherapydoes appear to improve local control, the lack of which is themajor cause of death among patients with unresectable cancer;combined therapy also appears to extend survival in these patients.They believe that the next steps are to further refine concomitantapproaches with novel regimens and schedules that enhance tumorsensitivity while minimizing toxicity; explore additional chemotherapyapproaches to eliminate micrometastases once lasting local controlhas been achieved; and involve long-term survivors in chemopreventiontrials to address the problem of second primary cancers in theseindividuals.