TPF Group Research Articles

Neoadjuvant Chemotherapy for Borderline Resectable Head and Neck Cancers: A Comparative Study of Three-Drug and Two-Drug Regimens in a Low- and Middle-Income Country (LMIC) Context.

Background Borderline resectable head and neck squamous cell carcinoma (HNSCC) presents a significant therapeutic challenge, particularly in low- and middle-income countries (LMICs) like India. Neoadjuvant chemotherapy (NACT) aims to downstage tumors to achieve operability, but the optimal regimen remains controversial due to varying efficacy and toxicity profiles. This study compares the efficacy and toxicity of a three-drug regimen (TPF: docetaxel, cisplatin, and 5-fluorouracil) with a two-drug regimen (taxane and platinum) in patients with borderline resectable HNSCC in an LMIC setting. Methods In this retrospective cohort study, a total of 90 patients with borderline resectable HNSCC were included. Forty-three patients received the TPF regimen (Arm A), while 47 received the taxane + platinum regimen (Arm B). The outcomes measured included conversion to operability, stage-specific outcomes, overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Statistical analyses included chi-square tests for categorical variables, Kaplan-Meier survival analysis, and Cox proportional hazards modeling for multivariate analysis. Results The conversion to operability was significantly higher in the TPF group (72% vs. 51%, p=0.03). Patients in Arm A also exhibited a trend toward higher pathological complete response (pCR) rates compared to Arm B (60% vs. 43%, p=0.08). The overall survival and progression-free survival were improved in the TPF group, although the study did not reach statistical significance in these endpoints due to the limited sample size. However, the TPF regimen was associated with significantly higher toxicity. Grade 3-4 neutropenia occurred in 55% of the patients in Arm A compared to 32% in Arm B (p=0.01), and mucositis was observed in 47% of Arm A patients compared to 19% in Arm B (p=0.002). Febrile neutropenia was also more frequent in the TPF group (28% vs. 13%, p=0.04). Multivariate analysis identified the chemotherapy regimen (HR=1.45, 95% CI 1.05-2.01, p=0.02) and baseline nutritional status (HR=1.78, 95% CI 1.12-2.82, p=0.01) as independent predictors of overall survival. Conclusion While the TPF regimen offers superior efficacy in terms of tumor downstaging and conversion to operability, its higher toxicity profile limits its applicability in resource-constrained settings, such as LMICs. The taxane + platinum regimen, although less effective in downstaging, presents a more favorable toxicity profile, making it a viable alternative for patients with comorbidities or poor performance status. The choice between these regimens should be individualized, considering the patient's overall health, nutritional status, and the availability of supportive care. Further research is warranted to optimize NACT strategies for patients in LMICs.

Comparing long-term efficacy and safety of GP versus TPF sequential chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a propensity score-matched analysis

PurposeTo evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).MethodsFrom 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups.ResultsA total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema.ConclusionNo significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen.

Comparison of the efficacy of carelizumab combined with chemotherapy and chemotherapy alone in the induction therapy of locally advanced hypopharyngeal carcinoma

Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

De-escalation treatment of patients with HPV-positive oropharyngeal squamous cell carcinoma.

e18052 Background: According to Globocan in 2020 were identified 98 412 new cases of oropharyngeal squamous cell carcinoma in the world. It was proved that the human papillomavirus (HPV) is a favorable prognostic factor. Patients with HPV-positive oropharynx cancer have higher indicators of progression-free survival (PFS) and overall survival (OS). As induction chemotherapy, the only TPF regimen (cisplatin/ docetaxel/ 5-fluorouracil) has been approved which has high toxic profile. Published results of randomized trials demonstrate the possibility of de-escalation CRT without reduction OS and PFS, but there is no data about safety of de-escalated IC regimen. Given the high toxicity of the standard regimen, as well as the presence of a favorable prognostic factor (HPV infection), since 2021 has started a prospective trial, investigating the possibility of use the dual-component IC regimen according to the TP scheme (cisplatin/ docetaxel). Objective: Improve the results of treatment of patients with locally advanced HPV- positive squamous cell carcinoma of the oropharynx by optimizing the scheme IC. Methods: In the prospective trial included 68 patients with p16-positive oropharyngeal squamous cell carcinoma (T3-4N0-1M0, or T1-4N2-3M0), who were divided into 2 equal groups. The research group received 3 cycles of IC to the de-escalated TP regimen and the control group according to the standard three-component TPF regimen. After completion IC patients of both groups had a standard CRT 70 Gy with carboplatin AUC 2.0 weekly. The primary endpoints were the assessment of objective response rate after the IC and toxicity. The Secondary endpoints: 1-year OS and PFS. Results: Complete response (CR) was achieved in 3 patients (8,8%), a partial response (PR) in 22 (64,7%), stable disease (SD) in 8 (23,5%) patients in the research arm. In the control arm: CR 4 patients (11,8%), PR 24 (70,6%), SD 6 (17,6%) patients. Both IC regimens demonstrated high efficacy rates, and there was no statistically significant ORR in the group (p=0,2133).Toxic manifestations were often observed in the arm of standard IC. The higher incidence of mucositis in the control group was statistically significant (p=0,025). The effect of IC regimen on subsequent CRT was also assessed. In the research arm, the time before the start of CRT was statistically significantly less than in the control arm (30 days vs 63 days, p=0,0035.). And the period of development mucositis of CRT in the TP group was longer than in the TPF group (34G vs 32G, p=0,0298). 1 year - PFS 94%, 1 year - OS 100% in the research group and 92% and 100% in the control arm. There was no statistically significant 1 year – PFS and 1 year - OS in the group (р=0,6547). Conclusions: The research scheme of IC demonstrated high results of an objective response, 1-year OS and 1 year - PFS, comparable to the standard TPF scheme, against the background of better tolerance.

Ganoderma spore lipid ameliorates docetaxel, cisplatin, and 5-fluorouracil chemotherapy-induced damage to bone marrow mesenchymal stem cells and hematopoiesis

BackgroundA triplet chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) is used to treat head and neck squamous cell carcinoma; however, it is toxic to bone marrow mesenchymal stem cells (BMSCs). We previously demonstrated that Ganoderma spore lipid (GSL) protect BMSCs against cyclophosphamide toxicity. In this study, we investigated the protective effects of GSL against TPF-induced BMSCs and hematopoietic damage.MethodsBMSCs and C57BL/6 mice were divided into control, TPF, co-treatment (simultaneously treated with GSL and TPF for 2 days), and pre-treatment (treated with GSL for 7 days before 2 days of TPF treatment) groups. In vitro, morphology, phenotype, proliferation, senescence, apoptosis, reactive oxygen species (ROS), and differentiation of BMSCs were evaluated. In vivo, peripheral platelets (PLTs) and white blood cells (WBCs) from mouse venous blood were quantified. Bone marrow cells were isolated for hematopoietic colony-forming examination.ResultsIn vitro, GSL significantly alleviated TPF-induced damage to BMSCs compared with the TPF group, recovering their morphology, phenotype, proliferation, and differentiation capacity (p < 0.05). Annexin V/PI and senescence-associated β-galactosidase staining showed that GSL inhibited apoptosis and delayed senescence in TPF-treated BMSCs (p < 0.05). GSL downregulated the expression of caspase-3 and reduced ROS formation (p < 0.05). In vivo, GSL restored the number of peripheral PLTs and WBCs and protected the colony-forming capacity of bone marrow cells (p < 0.05).ConclusionsGSL efficiently protected BMSCs from damage caused by TPF and recovered hematopoiesis.

Gemcitabine/Cisplatin versus docetaxel, cisplatin and 5-fluorouracil as induction chemotherapy in locally advanced nasopharyngeal carcinoma.

Induction chemotherapy followed by concomitant chemoradiation is the standard therapy for patients with locoregionally advanced NPC. There is a limitation of clinical studies that compare different induction regimens. The purpose of this work is to analyze the efficacy of two distinct chemotherapy regimens, docetaxel, cisplatin, and 5-fluorouracil (TPF) and gemcitabine/cisplatin (GP), in treating patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). We analyzed 81 patients initially presented with stage III-IVA NPC from January 2019 to June 2023. Participants were randomized in 1:1 ratio to obtain GP regimen or TPF regimen followed by concurrent CRT. The overall response rate was 97.5% after induction chemotherapy in both groups (In GP arm, 78% of patients achieved complete remission compared to 70% of patients treated with TPF regimen). The satisfactory tumor response to induction chemotherapy was linked with significant enhanced progression free survival [CI (3.37-13.92), HR=2.16, P=0.001] and overall survival [CI (3.717-9.443), HR=1.873, P=0.001]. The GP regimen was both efficacious and well-tolerated. Leucopenia and neutropenia (Grade 3-4) were significantly lower in GP group contrasted to in TPF group. There was no significant difference in the 3-year DFS and OS between GP and TPF protocols.

The effectiveness of a dual-component regimen of induction chemotherapy in the treatment of HPV-positive oropharyngeal squamous cell carcinoma

Given the favorable prognosis associated with HPV-positive oropharyngeal cancer, cancer care professionals are actively discussing the feasibility of de-escalating treatment strategy for this cohort of patients.The purpose of the study was to improve the treatment outcomes in patients with locally advanced HPV- positive oropharyngeal squamous cell carcinoma by identifying the optimal induction chemotherapy (ICH) regimen, in particular, by using a two-drug ICH.Material and Methods. The study included 27 patients with locally advanced (T3–4N0–1, or T1–4N2–3) P16-positive oropharyngeal squamous cell carcinoma. All patients received 3 cycles of ICT according to the TP (docetaxel + cisplatin) regimen. To assess the effect and toxicity of two-drug ICH, a control group of patients, who received ICH according to the standard three-drug TPF (docetaxel, cisplatin and 5FU) regimen, was formed.Results. In the TP group, complete response (CR) was achieved in 3 (11 %) patients, partial response (PR) in 17 (63 %), stable disease (SD) in 7 (26 %) patients. In the control group: CR 4 (20 %) patients, PR – 13 (60 %), SD – 4 (20 %) patients. The median follow-up time in the TP group was 9 months (range: 2 to 22 months). The 1-year progression-free (PFS) and overall survival (OS) rates were 88.2 % and 100 %, respectively. In the TPF group, the PFS and OS rates were 84.4 % and 100 %, respectively.Conclusion. The results revealed that TP ICH regimen was non-inferior to the standard TPF regimen in the rates of the objective response, 1-year OS and PFS.

Treatment Outcomes and Prognostic Factors of Concurrent Chemoradiotherapy With Docetaxel, Cisplatin, and Fluorouracil in Advanced Head and Neck Cancer.

Although the efficacy of docetaxel, cisplatin, and 5-Fluorouracil (TPF) as induction chemotherapy has been confirmed, the therapeutic outcome and prognostic factors of concurrent chemoradiotherapy (CCRT) should be investigated. Laboratory data of patients who underwent CCRT for advanced squamous cell carcinoma (SCC) of the head and neck were investigated to clarify the grade of side effects. Survival rates and prognostic scores were also calculated. Multivariate analysis was performed to examine the prognostic factors of the patients. Although there were significantly more advanced cases in the TPF group (n=72) than those in the cisplatin group (n=50), there were no significant differences in patient survival rates. In the TPF group, the lymphocyte count, albumin level, and C-reactive protein level of the patients before treatment were significantly correlated with patient outcomes. CCRT using the TPF regimen had remarkable treatment effects in advanced head and neck cancer.

A Randomized Phase III Trial Observed the Feasibility and Safety of Loplatin Combination Regimen of Sequential Loplatin in Locally Advanced Head and Neck SCC

<h3>Purpose/Objective(s)</h3> To compare the toxicity and efficacy of TL (docetaxel + lobaplatin (LBP)) regimen induction chemotherapy combined with LBP concurrent chemoradiotherapy (CRT) and TPF (docetaxel + cisplatin (DDP) + 5-fluorouracil) regimen induction chemotherapy combined with DDP concurrent CRT in the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). <h3>Materials/Methods</h3> Between August 2016 and October 2019, 87 patients with locally advanced HNSCC who were pathologically confirmed and met the enrollment criteria were randomly assigned to the experimental group and the control group. All patients adopted the chrono-chemotherapy mode. In the experimental group, TL regimen induction chemotherapy combined with LBP concurrent CRT was used. The control group received TPF induction chemotherapy combined with DDP concurrent CRT. Adjuvant chemotherapy regimen was the same as induction chemotherapy, for a total of two cycles. The endpoints of the study were the toxic and adverse effects, and overall survival (OS). <h3>Results</h3> The median follow-up was 35 months (19-57 months). (1) There was no significant difference in short-term objective response rate (ORR) between the TL group and the TPF group (p=0.208). (2) During induction chemotherapy, the incidence of nausea/vomiting of grade 1-2, hyperbilirubinemia and hyponatremia in the TL group and the TPF group was 10% vs. 51% (p<0.001), 14% vs. 36% (p=0.023) and 21% vs. 71% (p<0.001). The incidence of absolute neutrophil count reduction of grade 3-4 was 17% and 51% (p=0.001). During concurrent CRT, the incidence of creatinine elevation of grade 1-2, hyponatremia and hypokalemia in the TL group and the TPF group was 2% vs. 20% (p=0.010), 14% vs. 69% (p<0.001), 19% vs.62% (p<0.001). The incidence of thrombocytopenia of grade 3-4 was 24% and 4% (p=0.009). The 2-year OS of the TL group and the TPF group were 54.3% and 66.7% (p=0.342), and the 2-year progression-free survival rates (PFS) were 61.1% and 71.4% (p=0.200). <h3>Conclusion</h3> For locally advanced HNSCC, LBP combined regimen induction chemotherapy followed by LBP concurrent CRT may be a new choice for second-line treatment. LBP regimen had obvious advantages in reducing toxic and adverse effects, and the efficacy needs further follow-up verification.

Induction chemotherapy regimen of docetaxel plus cisplatin versus docetaxel, cisplatin plus fluorouracil followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Preliminary results of an open-label, noninferiority, multicentre, randomised, controlled phase 3 trial.

SummaryBackgroundInduction 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].

Efficacy of some selected neo-adjuvant chemotherapy regimens in the treatment of advanced oral squamous cell carcinoma, and their effects on immune function

Purpose: To investigate the clinical efficacy of different neo-adjuvant chemotherapy (NACT) regimens in the treatment of advanced oral squamous cell carcinoma (OSCC), and their influence on immune function of the patients.Methods: Advanced OSCC patients (n = 94) who received NACT served as subjects in this study. They were assigned to 2 different treatment groups. Forty patients received docetaxel and fluorouracil regimen (DF group), while 54 patients received taxotere, cisplatin and fluorouracil regimen (TPF group). Surgery was performed after NACT. Changes in clinical efficacy and immune function were monitored in both groups. The clinical baseline data of patients were assessed prior to the treatments. Independent indicators of prognosis were determined using Cox regression analysis (CRA).Results: Clinical treatment efficacy was higher in TPF group than in DF group (p &lt; 0.05). Objective remission rate (ORR) in DF group was lower than that in TPF group (p &lt; 0.05). After chemotherapy, both groups had increased levels of CD4+ and CD4+/CD8+, and reduced level of CD8+, when compared with pre-chemotherapy values, with higher levels of CD4+ and CD4+/CD8+ ratio, and lower level of CD8+ in TPF group than in DF group (p &lt; 0.05). Multivariate CRA revealed that the independent factors for prognosis of oral carcinoma (OC) were tumor node metastasis (TNM) stage and lymph node metastasis.Conclusion: These results indicate that TFP regimen improves clinical efficacy and immune function in patients with advanced OSCC.

The effect of combined TPF and intensity modulated radiotherapy after TPF induction chemotherapy on locally advanced nasopharyngeal carcinoma: a retrospective analysis.

To evaluate the efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF) regimen followed by intensity modulated radiotherapy (IMRT) on locally advanced nasopharyngeal carcinoma (NPC). A total of 150 patients with locally advanced NPC [American Joint Committee on Cancer (AJCC) 2009 stage IIIa-IVb] received 2 or 3 cycles of a TPF regimen as induction chemotherapy. A group of 67 participants (TPF group) continued to receive TPF chemotherapy and radiotherapy, and the remaining 83 participants (P group) received cisplatin chemotherapy and radiotherapy. A median follow-up of 35 months (4-66 months) showed that there was no significant difference between P group and TPF group in progression-free survival (PFS) and overall survival (OS). The incidence rate of myelosuppression at 3-4 degrees was 16.9% and 34.3% in the P group and TPF group (P=0.029), respectively, and the oral mucosa reaction at 3-4 degrees was 18.1% and 37.3% in the P group and TPF group, respectively (P=0.007). The 3-4-degree skin reaction in the P group and TPF group was 15.7% and 29.9% (P=0.030), respectively. The rate of liver function injury in the P group was significantly lower than that in TPF group (P<0.05). Compared with concurrent cisplatin chemotherapy and radiotherapy, the concurrent TPF regimen and IMRT showed no significant improvement in OS and PFS in patients with advanced NPC, but exhibited more severe hematologic toxicity, oral mucosal responses, skin reactions, and liver functional impairment.

A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P &gt; 0.05) and 97.8% (P &gt; 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.

Docetaxel and cisplatin induction chemotherapy with or without fluorouracil in locoregionally advanced nasopharyngeal carcinoma: A retrospective propensity score matching analysis.

PurposeTo investigate whether the addition of fluorouracil to docetaxel and cisplatin induction chemotherapy (IC) can truly improve the prognosis of patients with locoregionally advanced nasopharyngeal carcinoma (NPC).MethodsA total of 801 patients newly diagnosed with non‐metastatic locoregionally advanced NPC were included as the subjects. In this study, propensity score matching (PSM) was used for analysis of overall survival (OS), distant metastasis‐free survival (DMFS), progression‐free survival (PFS) and locoregional relapse‐free survival (LRRFS), and the chi‐squared test or Fisher's exact test was used to investigate toxic reactions.ResultsPatients received treatment with docetaxel and cisplatin (TP) or docetaxel, cisplatin and fluorouracil (TPF). With a median follow‐up time of 60 months (range: 5–124 months), the TPF group had better 5‐year OS (84.7% vs 79.0%; P = 0.037), PFS (84.6% vs 76.8%; P = 0.008) and DMFS (89.5% vs 82.3%; P = 0.004) than the TP group. After PSM, 258 patients were matched in each cohort. The Kaplan–Meier analysis showed that the 5‐year OS, PFS and DMFS were 85.5%, 84.2% and 89.2%, respectively, in the TPF group, higher than the 80.8%, 75.0% and 81.4%, respectively, in the TP group (P = 0.048, 0.009 and 0.006, respectively). Moreover, the multivariate analysis revealed that different IC regimens were independent prognostic factors for PFS and DMFS (P = 0.014 and 0.010, respectively).ConclusionThis study found that compared with the TP regimen, TPF induction chemotherapy is associated with improved survival in patients with locoregionally advanced NPC. TPF can produce more mucosal and nausea/vomiting adverse reactions than TP.

A Comparison of Acute Complications and Mortality Between Geriatric Knee and Hip Fractures: A Matched Cohort Study.

To compare acute complication and mortality rates for operatively treated, closed, isolated, low-energy geriatric knee fractures (distal femur [DFF] or tibial plateau [TPF]) with hip fractures (HFs). This is a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program. We identified all patients ≥ 70 years from 2011 to 2016 who underwent surgery for DFF, TPF, or HF. We recorded patient demographics, functional status, complications, and mortality. We matched DFF:TPF:HF patients on a 1:1:10 ratio based on age, sex, body mass index, baseline functional status, and comorbidity. We used the chi square, Fisher exact, and Mann Whitney U tests to compare unadjusted differences between groups and multivariable logistic regression to compare the risk of complications, readmission, or death while adjusting for relevant covariates. When compared with HF, patients in the DFF and TPF groups had longer length of stay and time to index surgery and were more likely to be discharged home. The rate of deep vein thrombosis was significantly higher in the TPF group (TPF = 3.9%, DFF = 1.3%, and HF = 1.2%, P = 0.005). Geriatric knee fractures pose a similar risk of acute complications, mortality, and readmission compared with patients with HF. Future studies investigating strategies to decrease risk in this patient cohort are warranted. Therapeutic Level III.

Comparison of Gemcitabine Plus Cisplatin vs. Docetaxel Plus Fluorouracil Plus Cisplatin Palliative Chemotherapy for Metastatic Nasopharyngeal Carcinoma.

Objective: Our study aimed to compare the efficacy and toxicity of two chemotherapy regimens, gemcitabine plus cisplatin (GP) vs. docetaxel plus, fluorouracil plus cisplatin (TPF), in metastatic nasopharyngeal carcinoma (NPC) patients.Methods: We retrospectively enrolled metastatic NPC patients between July 2006 and December 2016 who were treated with TPF or GP palliative chemotherapy (PCT). The association between the PCT regimens and survival conditions was evaluated by log-rank tests and the Cox proportional hazards model. A cohort was created using propensity score matching with the ratio of 1:1 to clarify the results of the multivariable Cox regression analyses. Overall survival (OS) was the primary endpoint.Results: Of 266 eligible patients, 186 and 80 patients, respectively, received TPF and GP regimen. No significant difference was demonstrated in the survival rate between the GP and TPF groups (3-year OS: 52.6 vs. 50.3%; P = 0.929). However, multivariable analysis suggested receiving GP as an independent protective factor (hazard ratio, 0.864; 95% confidence interval, 0.753–0.992; P = 0.042). In the matched cohort, treatment with GP was also associated with a significantly higher OS (3-year OS: 52.6 vs. 35.6%, P = 0.042). Subgroup analysis indicated that the superiority of GP reflected in patients with secondary metastases rather than primary metastases. The incidence of grade 3 to 4 treatment-related toxicity was more common in the TPF group than in the GP group.Conclusion: Our study suggested that GP might be superior to TPF for metastatic NPC patients, especially those with secondary distant metastases. Further studies are necessary to validate our results.

Systemic chemotherapy and sequential locoregional radiotherapy in initially metastatic nasopharyngeal carcinoma: Retrospective analysis with 821 cases.

We designed this retrospective study to explore the best treatment modality for patients with initially metastatic nasopharyngeal carcinoma (NPC). From 2008 to 2017, 821 patients were enrolled. Treatment modalities and prognostic factors were analyzed. Compared with chemotherapy alone and radiotherapy-based treatment, systemic chemotherapy-sequential locoregional radiotherapy to the nasopharyngeal primary tumor site were associated with a significantly increased 3-year overall survival (OS) rate (40.3%, 11.7%, and 22.9%, P < .001). The overall response rate of the paclitaxel combined with platinum and fluorouracil (TPF) regimen as first-line chemotherapy was higher than that of the paclitaxel plus platinum (TP) regimen (78.2% vs 70.0%, P = .038). A better OS was achieved in the TPF group compared to doublet drug regimens (3-year OS, 35.7% vs 25.3%, P < .001). Systemic chemotherapy-sequential locoregional radiotherapy may prolong OS and progression-free survival for selected patients with initially metastatic NPC.

Cost-effectiveness analysis of gemcitabine plus cisplatin versus docetaxel, cisplatin and fluorouracil for induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma.

Recently, patients who received induction chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma were found to have survival advantages compared with those receiving concurrent chemoradiotherapy alone in two large randomized trials. Based on these two trials, we present a cost-effectiveness analysis to compare gemcitabine and cisplatin (GP) versus cisplatin, fluorouracil, and docetaxel (TPF) for induction chemotherapy to treat locoregionally advanced nasopharyngeal carcinoma. We constructed a Markov model to compare the cost and effectiveness of GP versus TPF. Clinical data including the frequency of adverse events, recurrence and death obtained from two randomized phase III trials were used to calculate transition probabilities and costs. Health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollars per quality-adjusted life-year (QALY), were calculated, and incremental cost-effectiveness ratios less than $27,534.25/QALY (3×the per capita GDP of China, 2018) were considered cost-effective. One-way sensitivity and probabilistic sensitivity analyses explored the robustness of the model. Our base case model found that the total cost was $53,082.68 in the GP group and $45,482.66 in the TPF group. The QALYs were 6.82 and 4.11, respectively. The incremental cost-effectiveness ratio favoured the GP regimen, at an incremental cost of $2,804.44 per QALY. The probabilistic sensitivity analysis found that treatment with the GP regimen was cost-effective 100% of the time at a willingness-to-pay threshold of $27,534.25‬/QALY. In this model, GP was estimated to be cost-effective compared with cisplatin, fluorouracil, and docetaxel for patients with locoregionally advanced nasopharyngeal carcinoma from the payer's perspectives in the China.

Induction Therapy of Nituzumab Combined PF Regimen to Improve the Treatment Response and Tolerance of Locally Advanced Nasopharyngeal Carcinoma Undergoing the Concurrent Chemoradiotherapy: A Multi-Center Controlled Randomized Clinical Study

The role of targeted combined with chemotherapy-based induction therapy in locally advanced nasopharyngeal carcinoma with concurrent intensity-modulated radiotherapy(IMRT) is unclear. Through a multi-center randomized controlled study to investigate the safety and efficacy of the induction therapy of nimotuzumab combined with PF regimen (cisplatin + 5-fluorouracil) in the follow-up treatment of locally advanced nasopharyngeal carcinoma patients received concurrent chemoradiotherapy. From January 2015 to November 2017，We included 118 patients with stage III-IVa nasopharyngeal carcinoma from 8 tumor centers, 58 cases in NPF group (induction therapy of nimotuzumab combined with PF regimen) and 60 cases in TPF group (induction chemotherapy of docetaxel, cisplatin and fluorouracil regimen). After two cycles of induction therapy, all patients received cisplatin concurrent intensity-modulated radiotherapy (IMRT), and the safety and short-term efficacy of the two groups were compared. To analyze the correlation between the curative effect of induction therapy and EGFR expression. Until May 2018, all patients were treated and evaluated immediately after treatment. Compared with the TPF regimen , the nimotuzumab combined PF scheme was more effective for the cervical lymph node (p=0.036), and the response rate (CR+PR) was higher (60% vs 81%) , but there was no statistically significant difference in the curative effect of nasopharyngeal lesion and induction therapy (p=0.446,p=0.143); there was no statistically significant difference in immediate curative effect (p=0.449). Compared with the TPF group, although the incidence of 1 grade rash was significantly increased (p=0.012), the neutropenia and gastrointestinal reaction of NPF group was significantly reduced, the difference was statistically significant (p=0.028;p=0.049).The treatment tolerance of cisplatin during the IMRT stage is better in the NPF group, the gastrointestinal reaction, oral mucositis and radiation dermatitis were significantly reduced, and the difference was statistically significant (p=0.038,p=0.041,p=0.035).The expression rate of EGFR in the whole group was 94.9%. Compared with chemotherapy, patients with EGFR high expression can get a better treatment response (P=0.033) from the induction treatment of nituzumab monoclonal combined chemotherapy. For the locally advanced nasopharyngeal carcinoma patients received treated with cisplatin concurrent IMRT, the induction therapy of nimotuzumab combined with PF regimen has a better lymph node remission rate and mild adverse reactions. Patients had better tolerance in subsequent concurrent chemoradiochemotherapy , but the long-term efficacy requires further follow-up observation. Patients with EGFR high expression may gain more benefits from the induction treatment of EGFR combined chemotherapy.

Comparison of GP and TPF induction chemotherapy for locally advanced nasopharyngeal carcinoma

ObjectivesThis study aims to compare two induction chemotherapy regimens, TPF and GP, for patients with locally advanced nasopharyngeal carcinoma (NPC). Materials and methodsWe analyzed patients with newly diagnosed stage III-IVA NPC (excluding T3/T4N0, AJCC) between December 2010 and May 2015 who were treated with TPF or GP induction chemotherapy (IC) followed with concurrent chemoradiotherapy (CCRT) and those treated with CCRT alone. Treatment compliance, survival outcomes and grade 3–4 side effects were compared among these three groups. ResultsA total of 189 patients were eligible for this study, with 87 (46.0%), 71 (37.6%) and 31 (16.4%) in the TPF, GP and CCRT alone groups. All patients were followed for 3 years. There was no difference in the 3-year survival rate between GP- and TPF-treated patients. Disease-free survival (DFS) and overall survival (OS) were significantly improved in both IC groups compared with those in the CCRT alone group. Multivariable analysis suggested that patients with N3 had a higher risk of distant metastasis than those with N1-2. GP is not inferior to TPF regardless of different N categories. There were significant more grade 3–4 treatment-related toxicity in TPF group than in GP group. ConclusionOur study found that in locally advanced NPC, the GP induction chemotherapy regimen is equivalent to TPF in treatment outcomes, but with significant less grade 3–4 acute toxicity. Further studies are needed to validate our findings.