Study: Chemo+radiation therapy reduces cancer-specific deaths

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Adding concurrent-adjuvant chemotherapy to radiation therapy can reduce cancer-specific deaths, but increases acute toxicity for nasopharyngeal carcinoma patients, according to a study published online July 15 in the Journal of the National Cancer Institute.

“Radiotherapy (RT) is the primary treatment modality for nasopharyn­geal carcinoma, but the results for patients with advanced locoregional disease are unsatisfactory,” said Anne W.M. Lee of the department of clinical oncology at Pamela Youde Nethersole Eastern Hospital in Hong Kong and colleagues. The study was conducted in order to evaluate the long-term efficacy and safety of concurrent-adjuvant chemotherapy to radiotherapy (CRT) and to identify the most cost-effective treat­ment strategy for different risk groups.

The study included patients with nonkeratinizing naso­pharyngeal carcinoma presenting to the Pamela Youde Nethersole Eastern Hospital, Tuen Mun Hospital, Queen Mary Hospital and Queen Elizabeth Hospital, all of Hong Kong and Toronto-based Princess Margaret Hospital between March 16, 1999 and Jan. 30, 2004.

Patients were stratified according to participating center and NPC tumor (T1-2 vs T3-4) and nodal (N2 vs N3) staging cate­gories. Researchers randomly assigned 176 patients to RT only and 172 to CRT, using cisplatin every three weeks for three cycles in concurrence with radiotherapy, followed by cisplatin plus fluorouracil every four weeks for three cycles.

Overall failure-free rate and progression-free survival were considered primary endpoints of the study, with secondary endpoints including overall survival, locoregional failure-free rate, distant failure-free rate and acute and late toxicity rates, explained the authors.
Lee and colleagues determined that by adding chemotherapy, statistically significant improvement could be observed, with the five-year failure-free rate of CRT at 67 percent compared to radiotherapy at 55 percent and five-year progression-free survival for CRT at 62 percent versus RT 53 percent.

Despite these results, however, the cumulative incidence of acute toxicity increased by 30 percent with chemotherapy (CRT at 83 percent versus RT at 53 percent), and 12 percent of CRT patients presented with grade 4 severity of acute toxicity. However, the five-year late toxicity rate was not found to increase significantly (CRT, 30 percent compared to RT, 24 percent).

Mortality resulting from disease progres­sion was reduced by 14 percent with CRT, and five-year overall survival was considered similar (CRT at 68 percent compared to RT at 64 percent).

“[The] addition of chemotherapy to radiotherapy is an important strategy for improving tumor control of advanced nasopharyn­geal carcinoma because this treat­ment has potential for both enhancing the local effect of radio­therapy and eradicating micrometastases,” said the authors.

Lee and colleagues warned that while CRT significantly reduced failure and cancer-specific deaths compared with the results of the radiotherapy alone group, and while no statistically significant increase was noted in major late toxicity, an increase in noncancer deaths narrowed the overall CRT survival gain.

“Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radio­therapy for treating patients with advanced nasopharyn­geal carcinoma because the high­est priority is reduction of tumor relapse and cancer-specific deaths. However, patients should be duly informed that combined treatment induced statistically significantly more acute toxicities,” the study concluded.