Induction Chemotherapy May Boost Nasopharyngeal Cancer Survival

The addition of induction chemotherapy to a concurrent chemoradiotherapy regimen may improve locoregionally advanced nasopharyngeal failure-free survival

medwireNews: Phase III trial findings support the use of induction chemotherapy before concurrent chemoradiotherapy for patients with treatment-naive, locoregionally advanced nasopharyngeal carcinoma.

The open-label study of patients with non-keratinising stage III–IVB disease (excluding T3-4N0 tumours) was based on a regimen of three cycles of cisplatin (100 mg/m2 every 3 weeks) plus intensity modulated radiotherapy given in five daily fractions of 2.00–2.27 Gy per week for 6–7 weeks.

After a median of 45 months, the primary endpoint of 3-year failure-free survival was 80% for the 241 patients who were first given induction chemotherapy consisting of three cycles of docetaxel 60 mg/m2 and cisplatin 60 mg/m2, both given on day 1 of a 3-week cycle, plus continuous intravenous fluorouracil 600 mg/m2 per day on days 1 to 5.

This was significantly better than the 3-year failure-free survival rate of 72% achieved by the 239 patients who received only concurrent chemoradiotherapy, giving a hazard ratio (HR) of 0.68, report Jun Ma, from Sun Yat-sen University Cancer Center in Guangzhou, China, and co-workers.

Three-year distant failure-free survival was also significantly better with induction chemotherapy than with concurrent chemoradiotherapy alone, at 90% versus 83% and an HR of 0.59, although 3-year locoregional failure-free survival was comparable between the two groups at 92% versus 89%.

The rate of overall survival at 3 years was 92% with induction chemotherapy versus 86% with concurrent chemoradiotherapy alone, giving a significant HR of 0.59.

Induction chemotherapy was completed by 89% of patients, although 43% of patients experienced grade 3 or 4 adverse events, most commonly neutropenia (35%), leukopenia (27%), diarrhoea (8%) and stomatitis (6%).

Patients given induction therapy were less likely than those given only concurrent chemoradiotherapy to complete three cycles of cisplatin during chemoradiotherapy (30 vs 56%) and this resulted in a significantly lower mean relative dose intensity of concurrent cisplatin, at 71% versus 84%.

Overall, neutropenia was the most common grade 3 or 4 event reported over the total course of treatment, affecting 42% of patients given induction chemotherapy and 7% of those given only concurrent chemoradiotherapy. Leukopenia (41 vs 17%) and stomatitis (41 vs 35%) were also common.

“We recommend [docetaxel, cisplatin, fluorouracil] induction chemotherapy followed by concurrent chemoradiotherapy to patients with advanced nasopharyngeal carcinoma”, the authors write in The Lancet Oncology.

“[H]owever, long-term follow-up is required to assess the eventual efficacy and toxicity of this strategy”, they admit.

Michael Spiotto, from the University of Chicago Medical Center in Illinois, USA, commends the investigators for their study in an accompanying comment but agrees on the need for further evidence: “Because most metastases develop within 2 years of treatment, longer-term results are also needed to ensure that late toxicities, which might affect survival, do not temper the early benefits of controlling metastatic disease.”

In particular, he supports the design of a nasopharyngeal cancer trial comparing induction chemotherapy plus concurrent chemoradiotherapy against concurrent chemoradiotherapy with adjuvant chemotherapy.

“Such a trial would either validate induction chemotherapy or reaffirm the use of adjuvant chemotherapy, which has the potential for better compliance to concurrent chemoradiotherapy because delivery of concurrent chemoradiotherapy is not limited by toxicities from induction chemotherapy and for individualised treatment de-escalation with Epstein-Barr virus biomarkers, a focus of the ongoing NRG-HN001 trial”, the commentator observes.

References

Sun Y, Li W-F, Chen N-Y, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol; Advance online publication 26 September 2016. DOI: http://dx.doi.org/10.1016/S1470-2045(16)30410-7 

Spiotto MT. Return of induction chemotherapy in head and neck squamous cell cancers: is this time different? Lancet Oncol; Advance online publication 26 September 2016. DOI: http://dx.doi.org/10.1016/S1470-2045(16)30444-2

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016