Nasopharyngeal cancer is a particularly aggressive subset of head and neck cancers that frequently affects people of South East Asian origin and has a strong correlation with EBV infection. The current standard of care for locoregionally advanced nasopharyngeal carcinoma is definitive concurrent chemoradiotherapy with cisplatin. Recent evidence has demonstrated a benefit with platinum-based induction chemotherapy prior to chemoRT.

Despite this, patients have a high risk of disease relapse in both the locoregional and metastatic setting, even though a high proportion of patients achieve a complete clinical response after initial treatment.

All of this begs the question: what can we do to further reduce this risk of recurrence and death for patients with early NPC? An answer may lie in a 2021 study published in the Lancet in 2021 by Chen et al.

Between January 25, 2017 and October 25 2018, 406 patients were enrolled to randomly receive either metronomic capecitabine (650mg/m2 twice daily for up to a year) or observation following induction chemotherapy and combined chemoradiotherapy (CCRT). Patients were excluded if they had had previous chemotherapy, radiotherapy or surgery to the nasopharynx.

The primary endpoint was failure-free survival (FFS) at three years, defined as time from the date of randomisation to disease recurrence or death from any cause). Secondary endpoints included overall survival (OS), distant failure-free survival (DFFS), locoregional relapse-free survival (LRFS), safety and health-related quality of life (HRQOL).

Among patients who commenced metronomic capecitabine, the median duration of treatment was 12.1 months. The overall duration of follow-up was 38 months from the commencement of capecitabine. 14% of patients had disease recurrence in the capecitabine group, compared to 26% in the observation group.

FFS at 3 years in the capecitabine group was 85.3%, compared with 75.7% in the control group. Overall survival at 3 years was 93.3% in the capecitabine group, compared with 88.6% in the control group. Disease failure-free survival at 3 years was 89.4% in the capecitabine group, compared with 82.1% in the control group. Locoregional failure-free survival was 92.6% in the capecitabine group, compared with 87.8% in the control group.

Among patients who commenced metronomic capecitabine, dose interruptions due to adverse events were reported in 26% of patients, dose reductions were reported in 14%, and regimen discontinuation was reported in 5%.

Grade 1 or 2 adverse events were noted in 73% of patients in the capecitabine group, and 51% of patients in the control group. Grade 3 events occurred in 17% of patients in the capecitabine group, and in 6% of the control group. Only one Grade 4 event was noted in the capecitabine group (G4 neutropenia). There were no Grade 5 events.

The most common adverse event in the capecitabine group was hand-foot syndrome, reported in 58% of patients, 9% of whom had Grade 3 effects. The most common haematological toxicities included anaemia (35%) and leukopenia (27%). Other non-haematological adverse events included fatigue (27%) and nausea (22%).

The Bottom Line: patients with NPC have a higher-than-usual risk of disease recurrence. Incurable head and neck cancers frequently have not only terrible survival, but perhaps higher rates of morbidity and reduction of quality of life than any cancer type aside from high-grade glioblastomas. The use of metronomic capecitabine after definitive treatment for early NPC appears to reduce rates of recurrence and thus improve survival. However, this comes at a cost: there were significantly higher rates of toxicity in the capecitabine arm, compared to the observation arm. As a result, metronomic capecitabine is likely best suited for young, fit patients with high risk early NPC who are likely to tolerate the harder toxicity profile.

Source: Chen YP, Liu X, Zhou Q, Yang KY, Jin F et al. Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet. 2021 Jul 24;398(10297):303-313. doi: 10.1016/S0140-6736(21)01123-5. Epub 2021 Jun 7. PMID: 34111416. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01123-5/fulltext

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