Role of induction chemotherapy in the treatment of nasopharyngeal carcinoma

Abstract

An overview of the therapeutic benefit of induction chemotherapy for nasopharyngeal carcinoma will be presented. Nasopharyngeal cancer is a chemo-sensitive cancer; the effectiveness of induction chemotherapy followed by radiotherapy was first reported in the 1980s. The initial results showed conflicting conclusions. Despite the common experience of good initial response, only one of five randomized trials achieved significant improvement in event-free survival and none showed benefit in overall survival. Interests in induction chemotherapy waned in the late 1990s when the Intergroup-0099 Study made the first breakthrough by using concurrent-adjuvant chemoradiotherapy (CRT). A meta-analysis in 2006 confirmed that concurrent chemotherapy is the most potent sequence for combining with radiotherapy (RT) and the only sequence that showed significant survival benefit; induction chemotherapy per se could significantly reduce the risk of both locoregional failures and distant failures, but the impact did not translate into significant benefit in overall survival. Although subsequent trials did confirm the efficacy of regimens using cisplatin in concurrence with radiotherapy followed by combination of cisplatin and fluorouracil, controversy remains about the contribution of the adjuvant phase which is often poorly tolerated. Furthermore, there are concerns that improvement in distant failure remains unsatisfactory.

Hence, there are interesting interest to explore the benefit of induction-concurrent sequence, The induction phase is generally well-tolerated, full dose of potent chemotherapy combination could theoretically be more effective in eradicating micro-metastases. Furthermore, shrinkage of advanced locoregional disease, particularly those abutting neurological tissues, could enable wider margin for subsequent RT. Single-arm Phase II studies all reported encouraging early results, but two randomized Phase II trials showed conflicting results as to whether induction-concurrent CRT is superior to concurrent CRT. Five randomized Phase III trials are now on-going to confirm the therapeutic benefit, while four trials used concurrent CRT as the standard arm, the NPC-0501 Trial used the Intergroup concurrent-adjuvant CRT as the standard arm, 803 patients have been accrued and the preliminary results are being analyzed.

In conclusion, induction chemotherapy per se using cisplatin-based regimen with adequate dosage can achieve modest but significant improvement in tumor control. Adding induction chemotherapy to concurrent CRT is a promising strategy, confirmation by randomized trials is awaited.