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Importance: The treatment of metastatic nasopharyngeal carcinoma (mNPC) is a major challenge because of drug resistance and the toxic effects of chemotherapy., Objective: To evaluate the survival and toxicity outcomes and safety associated with the use of a modified low-dose fluorouracil protocol compared with standard regimens recommended in current guidelines for treatment of mNPC., Design, Setting, and Participants: This retrospective cohort study was based on data retrieved from electronic medical records from Sun Yat-sen University Cancer Center in China for 1397 patients with mNPC diagnosed from January 1, 2006, to December 31, 2017. Data analyses were conducted from October 1, 2020, to May 1, 2021., Exposures: Patients received chemotherapy, including platinum plus low-dose, long-term fluorouracil (PFLL); cisplatin plus standard dose, short-term fluorouracil (PFSS); cisplatin plus gemcitabine (GP); cisplatin plus taxane (TP); and cisplatin plus taxane plus fluorouracil (TPF)., Main Outcomes and Measures: The main outcomes included overall survival (OS); subsequent-line, treatment-free survival (sTFS), defined as the period from metastasis to the date requiring subsequent-line treatment or death; and the survival to toxicity ratio (STR), defined as person-year rate of OS divided by person-year rate of severe hematologic toxic effects. Cox regression models were used to compare the outcomes of patients receiving PFLL vs other regimens, adjusting for baseline characteristics., Results: Of 1397 patients with mNPC included in this study (1152 men; median age, 46 years [range, 18-70 years]) 134 received PFLL, 203 received GP, 330 received PFSS, 366 received TP, and 364 received TPF. A total of 764 patients died (75 in treatment group PFLL; 107 in group GP; 204 in group PFSS; 207 in group TP; and 171 in group TPF), and 979 patients had subsequent-line treatment or died, whichever occurred first (PFLL, 77; GP, 144; PFSS, 262; TP, 269; and TPF, 227). The median follow-up was 46.9 months (IQR, 25.4-82.4 months), and the 5-year OS rate among patients who received PFLL was 25.4% (95% CI, 16.7%-38.8%), which was not significantly different from that among patients who did not receive PFLL (30.2%; 95% CI, 27.1%-33.5%; P = .13) or who received GP (25.1%; 95% CI, 18.1%-35.0%; P = .81), PFSS (23.6%; 95% CI, 18.5%-30.0%; P = .80), or TP (28.1%; 95% CI, 22.8%-34.7%; P = .99) but was lower than that for patients who received TPF (40.4%; 95% CI, 34.7%-47.1%; P = .001). The 5-year sTFS among patients who received PFLL (24.1%; 95% CI, 15.4%-37.6%) was significantly higher than that among patients who did not receive PFLL (18.5%; 95% CI, 16.1%-21.3%; P = .005) or who received GP (14.3%; 95% CI, 9.1%-22.5%; P = .001) but similar to that for patients who received TPF (28.0%; 95% CI, 23.0%-34.0%; P = .74). The STR of PFLL was 0.81, substantially better than that of GP (0.41) and TPF (0.65)., Conclusions and Relevance: The results of this cohort study suggest that, compared with the use of standard treatment regimens, administration of PFLL was associated with similar OS but prolonged sTFS. PFLL also had better STR than other regimens, which could indicate less severe toxic effects. Thus, PFLL may be an option for first-line treatment of mNPC.

Background: Addition of oxaliplatin to capecitabine remains controversial for locally advanced rectal cancer (LARC). And cumulative oxaliplatin dose (COD) varied among clinical trials showing different therapeutic effects of this regimen. The objective of this study was to explore how COD affected tumor metastasis and patient survival., Methods: Totally 388 patients diagnosed with stage cII-III rectal cancer and treated with neoadjuvant chemoradiotherapy followed by radical surgery plus adjuvant chemotherapy were consecutively enrolled into this study and retrospectively reviewed. After grouping by total chemotherapy cycle (TCC), influences of COD on adverse effects and patients' survivals were analyzed in each group. Univariate and multivariate survival analyses were performed through Kaplan-Meier approach and COX proportional hazards model, respectively. Age, gender, anemia, differentiation, carcinoembryonic antigen, carbohydrate antigen 19-9, pretreatment clinical stage and postsurgical pathologic stage were used as covariates., Results: COD < 460 mg/m 2 emerged as an independent predictor of poorer overall, metastasis-free and disease-free survivals, in patients treated with TCC ≤ 7. The hazard ratios were 1.972, 1.763 and 1.637 (P values were 0.021, 0.028 and 0.041), respectively. But it was note-worthy that COD ≥460 mg/m 2 increased incidence of acute toxicities from 38.4 to 70.8% (P < 0.001). And in patients treated with TCC ≥ 8, COD failed to be a prognosticator., Conclusions: For LARC patients treated with insufficient TCC (≤ 7), oxaliplatin of ≥460 mg/m 2 might be needed to improve survival, though it might resulted in more acute toxicities.

Concurrent chemotherapy (CCT) is used in locally advanced nasopharyngeal carcinoma (NPC) for improved local control, which could also be achieved by intensity-modulated radiotherapy (IMRT). And for N2-3 NPC, distant metastasis is the more important cause of death. This study aims to evaluate the value of CCT in N2-3 NPC when neoadjuvant chemotherapy (NACT) of sufficient cycles is performed to eradicate distant metastasis. It enrolled 959 patients diagnosed with TxN2-3M0 NPC from July 2011 to December 2015 and treated with NACT of 3-4 cycles and IMRT. A propensity score matching (PSM) was made between patients treated with and without CCT (called the CCT and non-CCT groups, respectively), using a series of clinical characteristics (age, gender, T stage, N stage, NACT regimen, and EBV DNA) as covariates. After PSM, the two groups of patients were compared on survivals and acute toxicities. The results indicated that no difference was seen in the overall, disease-free, recurrence-free or metastasis-free survivals between the two groups. But compared with the CCT group, the non-CCT group had a lower patient proportion of myelosuppression, nausea/vomiting, oral mucositis, cervical dermatitis, xerostomia, and grade 3/4 myelosuppression and oral mucositis (all P values were <0.001). Hence, CCT appeared to bring more acute toxicities, instead of survival benefit, to N2-3 NPC patients treated with NACT of ≥3 cycles and IMRT. It should be used with cautions in these patients., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)