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Platinum-crosslinking polymeric nanoparticle for synergetic chemoradiotherapy of nasopharyngeal carcinoma.

ABSTRACT: Despite extensive use of radiotherapy in nasopharyngeal carcinoma (NPC) treatment because of its high radiosensitivity, there have been huge challenges in further improving therapeutic effect, meanwhile obviously reducing radiation damage. To this end, synergistic chemoradiotherapy has emerged as a potential strategy for highly effective NPC therapy. Here, we developed RGD-targeted platinum-based nanoparticles (RGD-PtNPs, denoted as RPNs) to achieve targeted chemoradiotherapy for NPC. Such nanoparticles consist of an RGD-conjugated shell and a cis-platinum (CDDP) crosslinking core. Taking advantage of RGD, the RPNs may effectively accumulate in tumor, penetrate into tumor tissues and be taken by cancer cells, giving rise to a high delivery efficiency of CDDP. When they are fully enriched in tumor sites, the CDDP loaded RPNs can act as radiotherapy sensitizer and chemotherapy agents. By means of X-ray-promoted tumor cell uptake of nanoparticle and CDDP-induced cell cycle arrest in radiation-sensitive G2/M phases, RPNs may offer remarkable therapeutic outcome in the synergistic chemoradiotherapy for NPC.

SUBMITTER: Ding Y

PROVIDER: S-EPMC8164009 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Platinum-crosslinking polymeric nanoparticle for synergetic chemoradiotherapy of nasopharyngeal carcinoma.

Ding Yuxun Y Xiao Xiaohui X Zeng Lingli L Shang Qiuping Q Jiang Wei W Xiong Sha S Duan Xiaohui X Shen Jun J Wang Ruibing R Guo Jinshan J Pan Yue Y

Bioactive materials 20210523 12

Despite extensive use of radiotherapy in nasopharyngeal carcinoma (NPC) treatment because of its high radiosensitivity, there have been huge challenges in further improving therapeutic effect, meanwhile obviously reducing radiation damage. To this end, synergistic chemoradiotherapy has emerged as a potential strategy for highly effective NPC therapy. Here, we developed RGD-targeted platinum-based nanoparticles (RGD-PtNPs, denoted as RPNs) to achieve targeted chemoradiotherapy for NPC. Such nanop ...[more]

PMID: 34095627

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Project description:PurposeInduction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma. However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced nasopharyngeal carcinoma.MethodsWe thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios and risk ratios using RevMan 5.1.ResultsSeven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that induction chemotherapy plus concurrent chemoradiotherapy improved overall survival (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001), progression-free survival (HR = 0.69, 95% CI: 0.60-0.80, P < 0.001), distant metastasis-free survival (HR = 0.65, 95% CI: 0.53-0.80, P < 0.001) and locoregional recurrence-free survival (HR = 0.68 95%, CI: 0.54-0.86, P = 0.001) versus concurrent chemoradiotherapy alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during concurrent chemoradiotherapy. However, the incidence of leukopenia and mucositis was similar in induction chemotherapy and induction chemotherapy plus concurrent chemoradiotherapy. Furthermore, the subgroup analysis showed better survival outcomes with induction chemotherapy plus concurrent chemoradiotherapy than with concurrent chemoradiotherapy alone in the triweekly cisplatin subgroup (all P < 0.01), whereas induction chemotherapy plus concurrent chemoradiotherapy could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR = 0.78, P = 0.02; and HR = 0.66, P = 0.03, respectively).ConclusionsInduction chemotherapy plus concurrent chemoradiotherapy improved survival outcomes in patients with locally advanced nasopharyngeal carcinoma versus concurrent chemoradiotherapy. For the weekly cisplatin regimen subgroup, it did not improve remote control or overall survival versus concurrent chemoradiotherapy alone, warranting further clarification.

Project description:Background: Patients with nasopharyngeal carcinoma (NPC) frequently developed the problem of malnutrition at the time of diagnosis. Chemoradiotherapy (CRT) can even worsen the situation. Therefore, nutritional intervention should be applied to prevent CRT-associated weight loss and interruption of CRT. However, it is still controversial if early nutritional intervention is beneficial to NPC patients with CRT. This study is to investigate the influence of early nutritional intervention on advanced NPC patients with CRT by evaluating the nutritional status and CRT treatment tolerance. Methods: A cohort of 78 stage III-IV nasopharyngeal carcinoma patients was divided into early (n=46) and late (n=32) nutrition intervention groups. The early group of patients received nutritional support at the beginning of CRT, whereas the late group received such a support until development of the side effects, like 50% required oral dietary intake or >10% weight loss. The data were collected and statistically analyzed. Results: There was no significant difference in baseline clinical characteristics between these two groups, suggesting that no selection bias occurred. Both groups of patients had weight loss at the end of CRT and 3 months thereafter. However, at the later time point, the early group started to regain their weight, while the late group continued to lose weight. At both time points, the early group had a lower percentage of weight loss than the late group. Similar results were also obtained for BMI, albumin, and pre-albumin levels (All p<0.05). Besides, the early group showed a lower rate of advanced mucositis, a lower percentage of patients with more than 3 days RT breaks, fewer days of RT delayed for toxicity, and a lower percentage of patients with unplanned hospitalizations (All p<0.05). A linear correlation was also found between the percentage of weight loss and the number of days of RT delayed. Conclusion: Early nutritional intervention provides beneficial outcomes to NPC patients by maintaining their nutritional status and enhancing CRT treatment tolerance. Our results also indicated early nutrition intervention may reduce the hospital cost and improve patients' life quality.

Project description:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p = 0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Project description:BackgroundN-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT).Patients and methodsBetween April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy.ResultsWith a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3-4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups.ConclusionIMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute toxicity rate.

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Platinum-crosslinking polymeric nanoparticle for synergetic chemoradiotherapy of nasopharyngeal carcinoma.

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Platinum-crosslinking polymeric nanoparticle for synergetic chemoradiotherapy of nasopharyngeal carcinoma.

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