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Induction Chemotherapy Boosts Nasopharyngeal Carcinoma Response

Use of induction chemotherapy significantly improves survival for patients undergoing chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma
03 Jun 2019
Anticancer Agents;  Head and Neck Cancers;  Radiation Oncology

Author:  By Lynda Williams, Senior medwireNews Reporter

medwireNews: Phase III trial findings indicate that giving gemcitabine and cisplatin chemotherapy before concurrent chemoradiotherapy significantly improves survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma (NPC). 

“This trial establishes [induction chemotherapy and chemoradiotherapy] as the standard of care in locally advanced NPC”, presenting investigator Juan Ma, from Sun Yat-sen University Cancer Center in Guangzhou, China, told delegates at the 2019 ASCO Annual Meeting in Chicago, Illinois, USA. 

“Induction [gemcitabine and cisplatin] can be an option for first-line treatment in this high-risk subgroup”, he said. 

The study, which was simultaneously reported in The New England Journal of Medicine, recruited patients with newly diagnosed stage III–IVB nonkeratinising NPC but excluded individuals with node-negative disease, who are at lower risk of metastasis.  

“The majority of patients had unfavorable prognostic features of N2 or N3 disease or bulky primary tumors (T3 or T4), all of which are surrogates for occult metastasis”, the authors note. 

All patients were scheduled to undergo three cycles of cisplatin 100 mg/m2 given every 3 weeks alongside 68–70 Gy of intensity-modulated radiation over 6.5 weeks. 

After a median of 42.7 months, 3-year recurrence-free survival (RFS) was achieved by 85.3% of the 242 patients who were randomly assigned to receive three cycles of gemcitabine 1 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1 every 3 weeks before beginning concurrent chemoradiotherapy. 

By comparison, the 3-year RFS rate was 76.5% for the 238 patients who were assigned to receive chemoradiotherapy alone, giving a significant hazard ratio (HR) for recurrence or death of 0.51 in favour of induction chemotherapy. 

This translated to a significant gain in overall survival at 3 years, with rates of 94.6% versus 90.3%, and a stratified HR for death of 0.43 that supported use of the induction chemotherapy. 

Distant RFS at 3 years was also significantly better with induction chemotherapy than without (91.1 vs 84.4%, HR=0.43), although the 3-year rate of locoregional RFS did not differ between the groups (91.8 vs 91.0%). 

“The efficacy of induction chemotherapy was due to the lower incidence of distant metastatic recurrences in the induction chemotherapy group than in the standard-therapy group, which probably explained the early overall survival advantage in the patients treated in the induction chemotherapy group”, Juan Ma et al believe. 

But the investigators note that the improved survival outcomes came “at the cost of a higher incidence of acute adverse events [AEs]” over the full treatment regimen, with safety analysis showing that 75.7% of 181 patients in the induction chemotherapy arm experienced grade 3–4 side effects compared with 55.7% of 132 controls. 

The most common grade 3–4 AE was mucositis in both the induction chemotherapy and standard treatment arms (28.9 and 32.1%, respectively), but receipt of induction chemotherapy was associated with higher rates of grade 3–4 neutropenia (28.0 vs 10.5%), nausea (23.0 vs 13.9%), vomiting (22.6 vs 13.9%), thrombocytopenia (11.3 vs 1.3%) and anaemia (9.6 vs 0.8%). 

Acute grade 1–2 nephrotoxicity was also more common in patients given induction chemotherapy (19.2 vs 11.4%), but acute ototoxicity was comparable between the groups. 

During induction chemotherapy, 38.9% of the 239 patients experienced acute grade 3–4 AEs, most commonly neutropenia (20.5%), leukopenia (10.9%) and vomiting (10.9%), although 96.7% of the group completed all three cycles.  

Late AEs were similar in the induction chemotherapy and chemoradiotherapy alone groups, except for an increased risk of grade 1–2 peripheral neuropathy (8.8 vs 1.7%). 

References 

Ma J, Zhang Y, Sun Y, et al. Gemcitabine and cisplatin (GP) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC): A phase 3, multicenter, randomized controlled trial. J Clin Oncol 37, 2019 (suppl; abstr 6003). 2019 ASCO Annual Meeting; Chicago, Illinois, USA: 31 May–4 June.

Zhang Y, Chen L, Hu G-Q, et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med; Advance online publication 31 May 2019. DOI: 10.1056/NEJMoa1905287

Last update: 03 Jun 2019

medwireNews (www.medwireNews.com  ) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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