Abstract
BackgroundChemoradiotherapy (CRT) with high cumulative doses (CDs) of cisplatin has been considered the standard of care for non-metastatic nasopharyngeal carcinoma (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 non-metastatic 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 non-metastatic 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.
Highlights
Chemoradiotherapy (CRT) with high cumulative doses (CDs) of cisplatin has been considered the standard of care for non-metastatic nasopharyngeal carcinoma (NPC)
Patients who received low CD of cisplatin were significantly older at diagnosis (p < 0.001) and had poorer smoking status (p = 0.003), lower LN stage (p = 0.016), higher incidences of comorbidities, including cardiac disease (p = 0.009), diabetes mellitus (p = 0.014), and hypertension (p = 0.043), and higher baseline creatinine clearance (CCr) (p < 0.001) than other groups
Univariate, but not multivariate, analysis showed that CD of cisplatin was significantly associated with overall survival (OS)
Summary
Chemoradiotherapy (CRT) with high cumulative doses (CDs) of cisplatin has been considered the standard of care for non-metastatic nasopharyngeal carcinoma (NPC). Several phase III clinical studies utilized high-dose cisplatin, either 100 mg/m2 every 3 weeks for three cycles [cumulative dose (CD), 300 mg/m2] or 40 mg/m2 weekly for seven cycles (CD, 280 mg/m2), for using concurrently with radiotherapy (RT) [5,6,7,8]. A post-hoc analysis from a Chinese prospective phase III study of patients with non-metastatic NPC concurrently receiving weekly cisplatin and radiotherapy (RT) reported a median cisplatin CD of 240 mg/m2, despite protocols requiring a CD of 280 mg/m2 [9]. Several retrospective studies demonstrated real-world data that majority of patients received less than the standard recommendations for cisplatin CD (280–300 mg/m2) [8, 10,11,12]. The lowest efficacious cisplatin CD during CRT remains unidentified
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