Optimal cumulative dose of cisplatin for concurrent chemoradiotherapy among patients with locally advanced nasopharyngeal carcinoma: a multicenter analysis in Thailand

Abstract IntroductionChemoradiotherapy (CRT) with high cumulative doses (CDs) of cisplatin has been considered the standard of care for locally advanced nasopharyngeal carcinoma (LA-NPC). However, given most patients’ inability to tolerate high CDs due to cisplatin-related toxicities, the optimal CD of cisplatin during CRT remains undetermined.MethodsPatients with LA-NPC who received CRT with cisplatin between 2007 and 2017 were identified through the Thai head and neck cancer multicenter database and then categorized according to cisplatin CD (mg/m2) received. All complications and cisplatin-related toxicities during CRT were recorded.ResultsWe identified 779 LA-NPC patients receiving low (£150; n=97), intermediate (151–250; n=411), and high (>250; n=271) CDs of cisplatin. Low CD patients had significantly lower mean actual radiation dose (p<0.001) and more radiotherapy delay (p=0.010), while intermediate CD patients had the least hospitalization (p<0.001). Overall, 39.3% of the patients experienced cisplatin-related toxicity, which was associated with poor overall survival (OS) (p=0.001). Acute kidney injury was observed in 7% in all patients, which was highest among low CD patients (15.5%; p=0.002). Intermediate CD patients had significantly longer median OS than the low and high groups (64 vs. 49.8 vs. 53.2, respectively; p=0.015). Univariate, but not multivariate, analysis showed that CD of cisplatin was significantly associated with OS.ConclusionCD of cisplatin during CRT was not an independent prognostic factor for OS. An intermediate CD induced minimal toxicity without compromising survival and should be considered the optimal CD. Nonetheless, a randomized phase 3 study evaluating the optimal CD of cisplatin is warranted.