Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients.

OBJECTIVES: To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log-rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. RESULTS: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71-0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67-0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. CONCLUSION: Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT.

Estimating the impact of new clinical trial proven cancer therapy and cancer chemoprevention on population mortality: the Karnofsky Memorial lecture.

PURPOSE: The 31-year "war on cancer" has focused largely on therapeutic (as opposed to preventative) cancer research, which, in both the public and private sector, has received the majority of funding. Meanwhile the prevention of cancer has received less attention. PATIENTS AND METHODS: We analyzed eight positive phase III therapeutic trials of the Southwest Oncology Group, and estimated how the observed improvements in survival from the new therapies would impact mortality at the population level (utilizing Surveillance, Epidemiology, and End Results-data). We compared these results with the impact of the Prostate Cancer Prevention Trial. The measure of impact was person-years saved in the first 5 years. RESULTS: Estimates of person-years saved in the first 5 years included 28,534 from improved treatment of localized bladder cancer and 26,241 from improved treatment of advanced lung cancer, representing, respectively, 31.4% and 2.8% of the person-years which could have been saved for these diseases (the "relative impact of new treatment on survival"). The new therapies from all eight positive phase III trials would have saved 114,641 person-years over the first 5 years. The estimate from the Prostate Cancer Prevention Trial was 99,441 person-years over the first 5 years. CONCLUSION: New cancer therapies have a proven and quantifiable impact on population mortality. Successful cancer prevention has a similarly large impact. However, federal funding for cancer prevention is less than half that of cancer treatment. As a result of its enormous potential for extending life, cancer prevention warrants increased funding and support from federal funding agencies.

Treatment of locally advanced head and neck cancer: historical and critical review.

BACKGROUND: Advanced squamous cell cancers of the head and neck have traditionally been associated with high rates of morbidity and mortality. Advances in management have improved outcomes for most of these patients. METHODS: The author reviews the historical progress in management of these difficult tumors and adds his own wide experience to describe and evaluate newer approaches to management. RESULTS: Over the last 10 years, overall survival rates for patients with head and neck cancers have improved as has quality of life. New standards of care have been defined for patients with nasopharyngeal cancer and for those with advanced unresectable disease. Organ preservation is more commonly achieved. CONCLUSIONS: Newer targeted therapies are likely to add to the progress that has already been achieved in the multimodality management of patients with head and neck cancers.

Nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is usually present as locally advanced (stage III or IV) disease. Before 1980, the primary treatment was radiotherapy. The 5-year survival rate of patients with stage IVM0 across the world was less than 30%. Local, regional, and systemic recurrences are high in these patients and contributed to the poor survival. Sequential chemotherapy followed by radiotherapy (especially with the combination of cisplatin and 5-fluorouracil infusion for three courses) resulted in a 5-year survival rate of up to 55% in patients with stage IV disease. Concurrent single-agent cisplatin and radiotherapy improved 5-year survival rate to up to 55% in these patients. Total treatment with concurrent chemoradiotherapy followed by adjuvant cisplatin and 5-fluorouracil infusion resulted in 5-year survival rate of approximately 75%. Reversing the sequence of treatment by giving chemotherapy followed by concurrent chemoradiotherapy may improve the 5-year survival to up to 90%. In patients with recurrent disease or systemic metastases, the chances of salvage and long remission (many years) is approximately 15% to 20% with the use of adequate and effective chemotherapy. Newer agents, alone or concomitant with radiotherapy, are being evaluated in these patients.