Paclitaxel liposome, cisplatin and 5-fluorouracil-based induction chemotherapy followed by de-escalated intensity-modulated radiotherapy with concurrent cisplatin in stage IVA–IVB childhood nasopharyngeal carcinoma in endemic area: a phase II, single-arm trial
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SUBMITTER: Luo D
PROVIDER: S-EPMC10491633 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:ImportanceInduction chemotherapy added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear.ObjectiveTo determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma.Design, setting, and participantsThis randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019. Patients were 18 to 65 years of age with treatment-naive, nonkeratinizing stage IVA to IVB nasopharyngeal carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1.InterventionsPatients were randomly assigned (1:1) to receive induction chemotherapy with two 21-day cycles of TPC (intravenous paclitaxel [150 mg/m2, day 1], intravenous cisplatin [60 mg/m2, day 1], and oral capecitabine [1000 mg/m2 orally twice daily, days 1-14]) or PF (intravenous cisplatin [100 mg/m2, day 1] and fluorouracil [800 mg/m2 daily, days 1-5]), followed by chemoradiotherapy.Main outcomes and measuresThe primary end point was failure-free survival in the intention-to-treat population. Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, tumor response, and safety.ResultsOverall, 238 eligible patients (187 men [78.6%]; median age, 45 years [range, 18-65 years]) were randomly assigned to receive TPC (n = 118) or PF (n = 120). The median follow-up duration was 48.4 months (IQR, 39.6-53.3 months). Failure-free survival at 3 years was 83.5% (95% CI, 77.0%-90.6%) in the TPC group and 68.9% (95% CI, 61.1%-77.8%) in the PF group (stratified hazard ratio [HR] for recurrence or death, 0.47; 95% CI, 0.28-0.79; P = .004). Induction with the TPC regimen resulted in a significant reduction in the risk of distant metastases (stratified HR, 0.49 [95% CI, 0.24-0.98]; P = .04) and locoregional recurrence (stratified HR, 0.40 [95% CI, 0.18-0.93]; P = .03) compared with the PF regimen. However, there was no effect on early overall survival (stratified HR, 0.45 [95% CI, 0.17-1.18]; P = .10). The incidences of grade 3 to 4 acute adverse events and late-onset toxicities were 57.6% (n = 68) and 13.6% (16 of 118), respectively, in the TPC group and 65.8% (n = 79) and 17.9% (21 of 117), respectively, in the PF group. One treatment-related death occurred in the PF group.Conclusions and relevanceThis randomized clinical trial found that induction chemotherapy with 2 cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with 2 cycles of PF, with no increase in the toxicity profile.Trial registrationClinicalTrials.gov Identifier: NCT02940925.
| S-EPMC8949760 | biostudies-literature
Project description:ObjectivesWe previously reported the efficacy of nab-paclitaxel added to cisplatin, 5-FU, and cetuximab (APF-C) followed by concurrent high dose bolus cisplatin and radiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). In this phase II trial, we determined the efficacy of APF (without cetuximab) followed by CRT in similar patients.Materials and methodsEligible patients had stage III-IV oropharynx (OP), larynx, or hypopharynx SCC and adequate organ function and performance status. T1 tumors were excluded. Patients were treated with three cycles of APF followed by CRT. Efficacy endpoints included two-year disease-specific survival (DSS), progression-free survival (PFS), overall survival (OS), and relapse rate.ResultsThirty patients were enrolled. Most patients were smokers (77%) with bulky T3/4 (73%) and N2/3 (83%) tumors. Analyses were stratified for human papilloma virus (HPV) status: HPV-related OPSCC (n=17; 57%) and HPV-unrelated HNSCC (n=13; 43%). With a minimum follow-up of 21months, relapse occurred in 1 (3%) patient. Two-year DSS was 94% in HPV-related OPSCC and 100% in HPV-unrelated HNSCC. Two-year PFS was 94% in HPV-related OPSCC and 100% in HPV-unrelated HNSCC. Two-year OS was 94% in HPV-related OPSCC and 92% in HPV-unrelated HNSCC. Causes of death were relapse (1), treatment-related mortality (1), and co-morbidity (1). Two patients with HPV-unrelated HNSCC treated with APF declined CRT and remained free of relapse at 36 and 28months of follow-up.ConclusionThis phase II trial demonstrated favorable two-year DSS, PFS, and OS and a low relapse rate in HPV-unrelated HNSCC and HPV-related OPSCC treated with APF followed by CRT.
| S-EPMC5105832 | biostudies-literature
Project description:IntroductionThis study aims to evaluate the efficacy of combining induction chemotherapy with concurrent chemoradiotherapy for patients with stage III-IVA nasopharyngeal carcinoma (NPC), particularly focusing on cases associated with Epstein-Barr virus infection. The primary focus is on treatment response and disease control.MethodsThis retrospective cohort study analyzed data from 81 patients with stage III-IVA NPC (excluding T3N0M0) treated with gemcitabine and cisplatin as induction chemotherapy, followed by concurrent chemoradiotherapy at the Vietnam National Cancer Hospital. Patient data and follow-up information were collected between June 2021 and June 2024, focusing on disease-free survival (DFS) as the primary outcome and secondary outcomes including factors affecting DFS and treatment-related toxicity.ResultsIn the initial 3-month period, 76 out of 81 patients achieved a complete response, and five patients achieved a partial response. The follow-up period averaged 18.7 ± 5.3 months, with a 2-year DFS rate of 77.6%. Key factors influencing DFS included patient age, N stage, disease stage, and treatment interruptions. Grade 3 toxicities observed included neutropenia (17.3%) and mucositis (32.1%), while grade 4 toxicity was limited to nausea (2.4%). Additionally, 2.6% of patients experienced delayed grade I-II toxicities, with some presenting grade III anorexia.ConclusionOur findings suggest that gemcitabine and cisplatin induction chemotherapy, followed by chemoradiotherapy, may result in a high response rate and effective disease control with manageable toxicity. However, further research is needed to evaluate long-term outcomes and potential delayed adverse effects to confirm these initial observations.
| S-EPMC11783467 | biostudies-literature
Project description:RationaleLimited patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) have achieved complete response (CR) from induction chemotherapy (IC). Neoadjuvant immunotherapy combined with chemotherapy has marked therapeutic effects in some locoregionally advanced solid tumors. However, its efficacy and safety of NPC have not been reported so far. The rapid response of neoadjuvant tislelizumab combined with chemotherapy on LA-NPC may be associated with long-term survival benefit.Patient concernsA 57-year-old male patient presented with a 2-month history of bloody nasal discharge and right neck mass for 2 weeks.DiagnosisThe patient was eventually diagnosed with nasopharyngeal nonkeratinizing undifferentiated cell carcinoma (stage IVA).InterventionsThe patient received tislelizumab combined with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) nab-paclitaxel plus cisplatin for 4 cycles, followed by cisplatin-based concurrent chemoradiotherapy (CCRT).OutcomesA partial response (PR) was achieved after 2 cycles of tislelizumab and nab-paclitaxel plus cisplatin, and CR was achieved after 4 cycles of neoadjuvant treatment. The duration of response lasted 24 months, and the patient was still in CR as of November 2022. The patient had no serious adverse event (AEs) during the treatment.LessonsThis case report showed that tislelizumab combined with cisplatin plus nab-paclitaxel followed CCRT for treatment of patients with LA-NPC may receive a fast and durable response with a manageable safety profile and long-term survival.
| S-EPMC9936014 | biostudies-literature
Project description:Induction chemotherapy treatment for nasopharyngeal carcinoma (NPC) is controversial. The aim of this study was to evaluate the treatment outcomes and toxicities between two induction chemotherapy regimens, with both followed by concurrent chemoradiotherapy. The first strategy used docetaxel, cisplatin and fluorouracil for induction chemotherapy (TPF), and the second utilised gemcitabine and cisplatin (GP). A retrospective analysis was performed on eligible NPC patients attending our hospital between May 2009 and Dec 2014. A total of 113 patients were enrolled with 58 patients receiving TPF and 55 receiving GP induction chemotherapy. Ninety-four patients (83.2%) were alive after 36-months follow-up. The median overall survival (OS) and progression-free survival (PFS) time were 48.3 and 39.7 months, respectively. The 3-year OS for the TPF regimen was 87.9% and 87.4% with GP chemotherapy (P = 0.928). The 3-year PFS of the TPF treatment was 84.5%, while it was 83.5% for the GP group (P = 0.551). Univariate analysis showed that lymph node metastasis was a significant PFS prognostic factor, while N3 stage was an independent predictor of PFS and distant failure-free survival (DMFS) in multivariate analysis. There were no significant differences in adverse toxicities or treatment efficacy between the chemotherapy regimens in the treatment of locoregionally advanced NPC.
| S-EPMC6197284 | biostudies-literature
Project description:BACKGROUND:Complete response (CR) at the primary tumor site as assessed by clinical examination following induction chemotherapy with PF (cisplatin and 5-fluorouracil [5-FU]) is a favorable predictive factor for overall survival and disease control in patients with locally advanced squamous cell carcinoma of the head and neck. In most series, the rate of CR at the primary site after induction PF was 20% to 30%. This study evaluated the efficacy and feasibility of induction nab-paclitaxel and cetuximab given with PF (ACPF) followed by definitive chemoradiation (CRT) in a phase 2 trial. METHODS:Patients with squamous cell carcinoma of the head and neck were treated with ACPF (nab-paclitaxel 100 mg/m(2) /week; cetuximab 250 mg/m(2) /week; cisplatin 75 mg/m(2) on day 1; 5-FU 750 mg/m(2) /day on days 1 through 3) every 21 days for 3 cycles followed by CRT (cisplatin 100 mg/m(2) on days 1, 22, and 43 of radiation therapy [RT]). CR at the primary tumor site after 2 cycles of ACPF was the primary endpoint. RESULTS:Thirty patients were enrolled, of which 22 (73%) had large (T3/T4) primary tumors. The CR rate at the primary tumor site after 2 cycles of ACPF was 53% and the overall response rate was 100%. Twenty-nine (96%) patients completed 3 cycles of ACPF, 26 (90%) completed definitive RT per protocol, and 22 of the 27 evaluable patients (81%) received > 2 of the 3 planned doses of cisplatin with RT. The estimated 2-year overall and progression-free survival rates were 84% and 65%, respectively. CONCLUSIONS:Induction ACPF resulted in a high CR rate (53%) at the primary tumor site even in large tumors and did not adversely affect delivery of definitive CRT. Further investigation of ACPF is warranted.
| S-EPMC3832987 | biostudies-literature
Project description:BackgroundInduction chemotherapy regimens of docetaxel and cisplatin plus fluorouracil (TPF) are currently clinically used for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but have well-known side effects, such as myelosuppression and diarrhea. A docetaxel plus cisplatin (TP) regimen was developed to decrease the toxic effects induced by fluorouracil. In this trial, we assessed whether the TP induction chemotherapy regimen was noninferior to the TPF regimen.MethodsWe performed an open-label, noninferiority, phase 3, multicentre, randomised, controlled trial at six centres in China. Eligible patients with NPC (stage III-IVA (excluding T3-4N0), Karnofsky's Performance Scoring ≥70) were randomly assigned (1:1) to receive either TP (docetaxel (75 mg per square meter, d1, intravenous infusion) and cisplatin (75 mg per square meter of body-surface area, d1, intravenous infusion)) or TPF (docetaxel (60 mg per square meter, d1, intravenous infusion) plus cisplatin (60 mg per square meter, d1, intravenous infusion) and 5-fluorouracil (600 mg per square meter, d1-d5, intravenous 120-hour infusion)) administered every 3 weeks for 3 cycles followed by concurrent chemoradiotherapy. The primary endpoint was failure-free survival at 2 years. Secondary endpoints included overall survival, safety, and treatment compliance. The trial was stopped early because of strong evidence for noninferiority (margin was -10%) of TP in failure-free survival. Efficacy analyses were performed in both the intention-to-treat and per-protocol trial populations and we included the patients who started treatment in each group for the safety analysis. The study was registered with chictr.org.cn, ChiCTR1800016337.FindingsBetween June 1, 2018 and October 31, 2021, we randomly assigned 361 patients to the TP (n = 181) or TPF (n = 180) induction chemotherapy group. The 2-year failure-free survival was 91·3% (95% CI 86·2-96·4) in the TP group and 82·4% (84·8-88·9) in the TPF group (P = 0·029). Patients in the TPF group had a higher frequency of grade 1 or 2 neutropenia (53 (30·0%) vs. 28 (15·7%); P = 0·0010), grade 1 or 2 diarrhea (20 (11·3%) vs. 9 (5·1%); P = 0·032), and grade 3 or 4 neutropenia (43 (24·3%) vs. 25 (14·0%); P = 0·014) in the induction chemotherapy period. There was no treatment-related death.InterpretationThe preliminary results revealed that TP induction chemotherapy regimen was found to be clearly non-inferior compared to the TPF regimen in failure-free survival, with a lower frequency of neutropenia, anaemia and diarrhoea. The more convenient and beneficial survival regimen of the TP regimen should be recommended in patients with LA-NPC.FundingThis study was supported by grants from the Natural Science Foundation of Guangdong Province, China [grant number 2021A1515011182], Natural Science Foundation of Guangdong Province, China [grant number 2022A1515012272], National Natural Science Foundation of China [grant number 82072029] and National Natural Science Foundation of China [grant number 81903037].
| S-EPMC9433608 | biostudies-literature
Project description:BackgroundThe effects of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in high-risk (stage III-IVb with EBV DNA≥4000 copies/ml) nasopharyngeal carcinoma (NPC) patients are unclear.MethodsA total of 325 high-risk NPC patients treated with IC+CCRT or CCRT alone who were treated with intensity-modulated radiation therapy (IMRT) between March 2007 and March 2013 were included. For each patient in the IC+CCRT group, a matched pair in the CCRT group was matching for: gender, age, T stage, N stage, clinical stage and WHO (World Health Organization) type. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS).ResultsThere were no significant differences in OS, PFS, DMFS, and LRFS between the IC+CCRT (148 patients) and CCRT (177 patients) groups. After matching, 103 paired patients were analyzed, and there were no differences between the IC+CCRT and CCRT groups regarding clinical outcomes. Based on the subgroup analysis of 156 very-high-risk patients (stage N2-3 with EBV DNA ≥4000 copies/ml), the 5-year OS of the IC+CCRT and CCRT groups was 84.3% and 67.5% (P =0.033), respectively. Based on our multivariate analysis, the treatment group was significantly associated with OS (P=0.034; HR0.451, 95%CI 0.216-0.941).ConclusionsIC+CCRT did not improve the clinical outcomes of high-risk NPC patients compared to CCRT alone. However, in very-high-risk patients, IC+CCRT treatment led to increased OS compared to patients received CCRT treatment alone.
| S-EPMC5045429 | biostudies-literature
Project description:ObjectiveFor locally advanced nasopharyngeal carcinoma (LA-NPC) patients, high incidences of distant metastases and severe treatment related toxicities are the main obstacles needed to be overcome. Raltitrexed, a specific thymidylate synthase inhibitor with a convenient administration schedule, has an acceptable and manageable toxicity, and possesses radio-sensitizing properties. To investigate the efficacy and safety of raltitrexed and cisplatin induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT) in patients with LA-NPC, a phase II clinical study was conducted.MethodsSixty eligible patients with LA-NPC were enrolled into this study. A raltitrexed-cisplatin combination was used as part of an IC+CCRT regimen. Raltitrexed-cisplatin IC was given once every 3 weeks (q3w) for two cycles, followed by raltitrexed-cisplatin based CCRT q3w for two cycles. Intensity-modulated radiotherapy (IMRT) was given for all enrolled patients.ResultsAll patients were included in survival analysis according to the intent-to-treat principle. The objective response rate (ORR) 3 months after treatment was 98%. The 2-year overall survival (OS) rate was 92%. The median relapse-free survival (RFS) time was 30.5 [95% confidence interval (95% CI), 28.4-32.3] months. The 2-year RFS rate was 85%. The 2-year local failure-free survival (LFFS) rate was 97% and the 2-year distant metastasis-free survival (DMFS) rate was 88%. Acute toxicities were mostly grade 2 and 3 reactions in bone marrow suppression, gastrointestinal side effect and oropharyngeal mucositis. Only two patients occurred grade 4 acute toxicities, one was bone marrow suppression and the other was dermatitis radiation.ConclusionsThe combination of raltitrexed and cisplatin has a comparable efficacy to those in standard first-line therapy.
| S-EPMC7666785 | biostudies-literature
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.
| S-EPMC5870479 | biostudies-literature