Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials.

PURPOSE: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. METHODS AND MATERIALS: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. RESULTS: No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053). CONCLUSIONS: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.

Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: a pooled data analysis of two phase III trials.

PURPOSE: To evaluate the long-term outcome in patients with nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and radiotherapy (CRT) versus radiotherapy alone (RT). PATIENTS AND METHODS: The data from two phase III studies comparing CRT with RT in NPC were updated and pooled together for analysis. A total of 784 patients were included for analysis, with an equal number of patients in both arms. Induction chemotherapy consisted of two to three cycles of cisplatin, bleomycin, and fluorouracil, or cisplatin and epirubicin. RT was given to the nasopharynx and neck using megavoltage radiation (median dose, 70 Gy). The median follow-up time for surviving patients was 67 months. Analysis was based on intention to treat. RESULTS: The addition of induction chemotherapy to RT was associated with a decrease in relapse by 14.3% and cancer-related deaths by 12.9% at 5 years. The 5-year relapse-free survival rate was 50.9% and 42.7% in the CRT and RT arm, respectively (P = .014), and the 5-year disease-specific survival rate was 63.5% and 58.1% in the CRT and RT arm, respectively (P = .029). The 5-year overall survival rate was 61.9% and 58.1% in CRT and RT arm, respectively (P = .092). The incidence of locoregional failure and distant metastases was reduced by 18.3% and 13.3% at 5 years, respectively, with induction chemotherapy. There was no significant difference in the treatment failure patterns between the two arms. CONCLUSION: The addition of cisplatin-based induction chemotherapy to RT was associated with a modest but significant decrease in relapse and improvement in disease-specific survival in advanced-stage NPC. However, there was no improvement in overall survival.

Prognostic impact of hemoglobin levels on treatment outcome in patients with nasopharyngeal carcinoma treated with sequential chemoradiotherapy or radiotherapy alone.

BACKGROUND: The goal of the current study was to investigate the impact of hemoglobin (Hb) levels on treatment outcome in a randomized Phase III trial of patients with nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by radiotherapy or with radiotherapy alone. METHODS: Between September 1989 and August 1993, 334 patients with advanced NPC were entered into a randomized trial comparing 3 cycles of induction chemotherapy (cisplatin and epirubicin) followed by radiotherapy with radiotherapy alone. Only evaluable patients who completed radiation were included in the analysis (n = 286). Patients were stratified into normal and low Hb groups according to baseline, preradiation, and midradiation Hb levels. Local recurrence-free, distant metastasis-free, and disease-specific survival rates were estimated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox model. RESULTS: In the chemotherapy arm, the mean baseline, preradiation, and midradiation Hb levels were 13.6, 11.0, and 11.8 g/dL, respectively. In the radiotherapy arm, the mean baseline/preradiation and midradiation Hb levels were 13.7 and 12.9 g/dL, respectively. A midradiation Hb level < or = 11 g/dL was associated with significantly poorer 5-year local recurrence-free (60% vs. 80%; P = 0.0059) and disease-specific survival rates (51% vs. 68%; P = 0.001), with no difference in distant metastasis-free rates (69% vs. 67%; P = 0.83). No significant difference in treatment outcome according to baseline or preradiation Hb levels was noted. Multivariate analysis showed that a low midradiation Hb level, but not a low baseline or preradiation Hb level, was an independent predictor of local disease recurrence and malignancy-related death. CONCLUSIONS: The current study showed that midradiation Hb level was an important prognostic factor with respect to local control and survival in patients with NPC. The high incidence of anemia after chemotherapy has a negative impact on treatment outcome, and this condition may reduce the benefit of induction chemotherapy. Attempts to correct anemia during radiation and the impact of anemia on treatment outcome requires further study.

Randomized evaluation of the audiologic outcome of ventilation tube insertion for middle ear effusion in patients with nasopharyngeal carcinoma.

OBJECTIVE: Complications after ventilation tube insertion for middle ear effusion in patients with nasopharyngeal carcinoma are frequent. This may compromise the overall benefit obtained from the procedure. This study evaluates the hearing improvement after tube insertion compared with observation alone to see if the benefits of the procedure outweigh its potential complications. DESIGN: Prospective randomized controlled trial. SETTING: Full clinical and emergency otolaryngologic services hospital in an academic institution. METHODS: Patients with nasopharyngeal carcinoma and middle ear effusion were randomized for preradiotherapy ventilation tube insertion or observation. Audiologic assessment with a pure-tone audiogram was performed before the procedure, after ventilation tube insertion, and at fixed intervals after irradiation. Audiologic outcome was compared between the two groups. MAIN OUTCOME MEASURE: Air-conduction threshold and air-bone gap on a pure-tone audiogram at different intervals after radiotherapy. RESULTS: There was no significant difference in hearing threshold changes between the two groups for up to 4 years. Both groups had air-bone gap improvement following radiotherapy and the improvement was not significantly different between the two groups. The proportion of patients with closure of the air-bone gap on follow-up was not different between the two groups. CONCLUSIONS: Ventilation tube insertion before radiotherapy did not offer additional hearing benefit when compared with observation alone. The procedure had no deleterious effect on hearing for up to 4 years.