A prospective, randomized trial comparing neoadjuvant chemotherapy with radiotherapy alone in patients with advanced nasopharyngeal carcinoma

Abstract

BACKGROUND A prospective, randomized study was performed to determine the efficacy of neoadjuvant chemotherapy over radiotherapy alone in patients with locally advanced nasopharyngeal carcinoma. METHODS From January 1991 to December 1998, 80 patients were enrolled in this study. Patients with locoregional carcinoma of the nasopharynx were randomized to receive two courses of chemotherapy, consisting of cisplatin and 5‐fluorouracil (CDDP‐5FU), that were administered before radiation therapy (CT arm) or radiotherapy alone. The patients who received neoadjuvant chemotherapy were treated with radiation therapy, which was scheduled to commence 2 weeks after the second course chemotherapy. RESULTS With a median follow‐up of 49 months, a trend toward improved overall survival or disease free survival favoring the CT arm was observed (5‐year overall survival rate, 60% vs. 48%; 5‐year disease free survival rate, 55% vs. 43%), although this difference was not significant. There were no differences in locoregional failure free survival between the two arms. However, metastasis free survival favored the CT arm, although this difference was not significant. The results also demonstrated that most patients in the CT arm who experienced recurrent disease developed locoregional recurrences before distant metastases, suggesting that improvements in locoregional control may lead to improved disease free survival. CONCLUSIONS The use of CDDP‐5FU chemotherapy prior to radiotherapy in patients with nasopharyngeal carcinoma did not result in a significant improvement in disease free survival or overall survival. However, there was a positive tendency in favor of the CT arm for distant metastasis free survival, although there was no improvement in the locoregional recurrence free survival rate. Cancer 2002;94:2217–23. © 2002 American Cancer Society. DOI 10.1002/cncr.10473

Induction Chemotherapy Followed by Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy with or without Adjuvant Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: Meta-analysis of 1,096 Patients from 11 Randomized Controlled Trials

“…Perhaps, this might be related with the fact that induction chemotherapy delayed the time of radiotherapy. In 2002, Hareyama et al (Hareyama et al, 2002) reported a randomized Phase III trial comparing neoadjuvant chemotherapy followed by radiotherapy with radiotherapy alone in patients with advanced NPC. With a median follow-up of 49 months, no significant differences were found in 5-year overall survival (60% versus 48%) and 5-year disease free survival (55% versus 43%).…”

Outpatient weekly neoadjuvant chemotherapy followed by radiotherapy for advanced nasopharyngeal carcinoma: high complete response and low toxicity rates

“…To the best of our knowledge, there have been nine phase III randomised trials to investigate the role of combined chemoradiotherapy in NPC so far (Rossi et al, 1988;Chan et al, 1995Chan et al, , 2002Cvitkovic and INCSG, 1996;Al-Sarraf et al, 1998;Chua et al, 1998;Ma et al, 2001;Chi et al, 2002;Hareyama et al, 2002). Table 5 summarises the results.…”

“…Although this is the only randomised trial of positive results in survival analysis, its wide application to non-American NPC patients should be considered with caution. First, about 30% patients of the Intergroup study have WHO type I histology (keratinising squamous cell carcinoma), but European (Cvitkovic et al, 1996), Japanese (Hareyama et al, 2002), or Chinese (Chan et al, 1995(Chan et al, , 2002Chua et al, 1998;Ma et al, 2001;Chi et al, 2002) series usually contain less than 5% WHO type I patients. Second, the survival data of radiotherapy alone are unexplainedly low -24% 3-year progression-free survival rate and 47% 3-year overall survival rate.…”

Induction chemotherapy in the treatment of nasopharyngeal carcinoma: Clinical outcomes and patterns of care

“…Patients were considered to have received induction chemotherapy if it was started ≥43 days before the start of RT. This time point was chosen as it would allow for administration of 2‐3 cycles of induction chemotherapy used in recent trials 7, 8, 10. Patients were considered to have received concurrent CRT if chemotherapy started within 21 days after the start of RT as this would allow for overlap of at least 2‐3 cycles of concurrent chemotherapy with RT.…”

“…Alternatively, induction chemotherapy is thought to be better tolerated and may result in early eradication of micrometastasis, leading to the hypothesis that it may result in improved survival. However, this has been controversial as several studies have found a survival benefit with this approach, while others have not 8, 9, 10. A meta‐analysis based on individual patient data has showed no benefit with induction chemotherapy 11.…”