Cisplatin Regimen Research Articles

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Salvage Therapy of Relapsed/Refractory Germ Cell Tumors: A Single-Center Experience

Introduction: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. Methods: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1–3 plus etoposide 750 mg/m2 on days 1–3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. Results: The median age of the patients was 31 (range 18–62). The median follow-up was 31.1 months (95% CI, 28.9–33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1–43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. Conclusion: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.

Corrigendum: Anti-tumor Efficacy of a Bevacizumab Preconditioning followed by Etoposide and Cisplatin Regimen in Human Epidermal Growth Factor Receptor-2-Positive Breast Cancer Brain Metastasis Refractory to Whole Brain Radiotherapy

Corrigendum: Anti-tumor Efficacy of a Bevacizumab Preconditioning followed by Etoposide and Cisplatin Regimen in Human Epidermal Growth Factor Receptor-2-Positive Breast Cancer Brain Metastasis Refractory to Whole Brain Radiotherapy

Atezolizumab plus modified docetaxel, cisplatin, and fluorouracil as first-line treatment for advanced anal cancer (SCARCE C17-02 PRODIGE 60): a randomised, non-comparative, phase 2 study

The modified docetaxel, cisplatin, and fluorouracil (mDCF) regimen has shown efficacy and safety as first-line treatment for advanced squamous cell carcinoma of the anus, making it a standard regimen. Inhibitors of programmed cell death protein 1 and its ligand, such as pembrolizumab, nivolumab, retifanlimab, avelumab, and atezolizumab, have shown some antitumour activity as monotherapy in advanced squamous cell carcinoma of the anus that is refractory to chemotherapy. This phase 2 study evaluated the combination of mDCF and atezolizumab as first-line treatment in advanced squamous cell carcinoma of the anus. In this randomised, open-label, non-comparative, phase 2 study, participants from 21 centres (academic, private, and community hospitals and cancer research centres) across France with chemo-naive, metastatic, or unresectable locally advanced recurrent squamous cell carcinoma of the anus, aged 18 years or older, and with an Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly allocated (2:1) to receive either atezolizumab (800 mg intravenously every 2 weeks up to 1 year) plus mDCF (eight cycles of 40 mg per m2 docetaxel and 40 mg per m2 cisplatin on day 1 and 1200 mg per m2 per day of fluorouracil for 2 days, every 2 weeks intravenously; group A) or mDCF alone (group B). Randomisation was done centrally using a minimisation technique and was stratified by age (<65 years vs ≥65 years) and disease status. The primary endpoint was investigator-assessed 12-month progression-free survival in the modified intention-to-treat population in group A (35% for the null hypothesis and 50% for the alternative hypothesis). This trial is registered with ClinicalTrials.gov, NCT03519295, and is closed to new participants. 97 evaluable participants (64 in group A and 33 in group B) were enrolled between July 3, 2018, and Aug 19, 2020. The median follow-up was 26·5 months (95% CI 24·8-28·4). The median age of participants was 64·1 years (IQR 56·2-71·6), and 71 (73%) were female. 12-month progression-free survival was 45% (90% CI 35-55) in group A and 43% (29-58) in group B. In participants with a PD-L1 combined positive score of 5 or greater, 12-month progression-free survival was 70% (95% CI 47-100) in group A and 40% (19-85) in group B (interaction p=0·051) Both groups showed high compliance. Adverse events of grade 3 or higher were observed in 39 (61%) participants in group A and 14 (42%) in group B. The most common grade 3-4 adverse events were neutropenia (nine [14%] participants in group A vs five [15%] in group B), anaemia (nine [14%] vs one [3%]), fatigue (three [5%] vs four [12%]), and diarrhoea (seven [11%] vs one [3%]). Serious adverse events occurred in 16 (25%) participants in group A and four (12%) in group B, and these were mDCF-related in seven (11%) participants in group A and four (12%) in group B. Atezolizumab-related serious adverse events occurred in nine (14%) participants in group A, including grade 2 infusion-related reaction in three (5%), grade 3 infection in two (3%), and grade 2 colitis, grade 3 acute kidney injury, grade 3 sarcoidosis, and a grade 4 platelet count decrease each in one participant (2%). There were no treatment-related deaths. Despite a higher incidence of adverse events, combining atezolizumab with mDCF is feasible, with similar dose intensity in both groups, although the primary efficacy endpoint was not met. The predictive value of a PD-L1 combined positive score of 5 or greater now needs to be confirmed in future studies. GERCOR, Roche.

Clinical analysis of 12 cases of ovarian yolk sac tumor

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Long-term survival, toxicities, and the role of chrono-chemotherapy with different infusion rates in locally advanced nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy: a retrospective study with a 5-year follow-up.

This study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC). Our retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a "MELODIE" multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed. After a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects. Long-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.

Comparison of efficacy and safety of 5-FU or capecitabine combined with cisplatin and docetaxel (mDCF and mDCX) as a first-line chemotherapy regimen in her 2-negative metastatic gastric cancer patients: A retrospective study.

The prognosis of metastatic gastric cancer (GC) is poor, with a median survival time of less than a year. Capecitabine is a prodrug, metabolized by thymidine phosphorylase to its cytotoxic metabolite (5-FU). Few studies have compared capecitabine and 5-FU in mGC. In this retrospective study, we compared the efficacy and safety of modified DCF (mDCF) (docetaxel, cisplatin, and 5-FU) and modified DCX (mDCX) (docetaxel, cisplatin, and capecitabine) regimens for first-line treatment in patients with mGC. The study included 112 mGC patients treated with either mDCF (n = 69) or mDCX (n = 43) between 2010 and 2021. Demographic data, response rate, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. The complete response rate in the mDCF group was 10.1%, whereas the complete response rate in the mDCX group was 2.3%. The partial response rate for mDCF and mDCX were 29% and 37%, respectively. The 2 treatment arms of the study had the same objective rate of response and disease control rate (DCR). PFS and OS rates were comparable between the 2 groups. The median PFS in the mDCF and mDCX arms were 6.0 months (95% CI, 4.87-7.14) and 5.0 months (95% CI, 4.10-5.90) respectively (P = .08). The median OS in the mDCF and mDCX arms were 9.0 months (95% CI, 7.53-10.47) and 9.0 months (95% CI, 6.87-11.11) respectively (P = .07). Neutropenia, asthenia, stomatitis, and nausea/vomiting were the most frequently reported grade 3 to 4 adverse events (AEs). The rates of grade 3/4 AEs and dose reduction were comparable between the 2 groups. There was no treatment discontinuation due to grade 3 to 4 AE. As a first-line treatment for patients with mGC, mDCX and mDCF regimens have comparable efficacy and tolerability profiles.

ASSESSMENT OF UNWANTED EFFECTS OF CONCURRENT CHEMORADIOTHERAPY FOR NASOPHARYNGEAL CARCINOMA, AT THE NATIONAL OTORHINOLARYNGOLOGY HOSPITAL OF VIETNAM, FROM 2019 TO 2023

Purpose: Assessment of the unwanted effects of concurrent chemoradiotherapy for nasopharyngeal carcinoma. Subjects and methods: A retrospective combined prospective study and description of 53 patients with stage II-IVA nasopharyngeal carcinoma, treated with concurrent chemoradiotherapy by the cisplatin regimen on days 1, 22 and 43 at the National Otorhinolaryngology Hospital of Vietnam from 2019 to 2023. Results: The incidence of grade 3 toxicity on the hematopoietic and non-hematopoietic systems, and late complications occurred at a low rate. Specifically: toxicities of leukopenia and granulocytopenia at grade 3 were 17.0%, and 7.5% respectively; toxicity: dermatitis, mucositis, and, nausea at grade 3 were 3.8%, 18.9%, and 5.7%, respectively. Late complications of xerostoma and skin fibrosis at grade 3 were 18.9% and 1.9%, respectively.

Is there a preferred platinum and fluoropyrimidine regimen for advanced HER2-negative esophagogastric adenocarcinoma? Insights from 1293 patients in AGAMENON–SEOM registry

BackgroundThe optimal chemotherapy backbone for HER2-negative advanced esophagogastric cancer, either in combination with targeted therapies or as a comparator in clinical trials, is uncertain. The subtle yet crucial differences in platinum-based regimens' safety and synergy with combination treatments need consideration.MethodsWe analyzed cases from the AGAMENON–SEOM Spanish registry of HER2-negative advanced esophagogastric adenocarcinoma treated with platinum and fluoropyrimidine from 2008 to 2021. This study focused exclusively on patients receiving one of the four regimens: FOLFOX (5-FU and oxaliplatin), CAPOX (capecitabine and oxaliplatin), CP (capecitabine and cisplatin) and FP (5-FU and cisplatin). The aim was to determine the most effective and tolerable platinum and fluoropyrimidine-based chemotherapy regimen and to identify any prognostic factors.ResultsAmong 1293 patients, 36% received either FOLFOX (n = 468) or CAPOX (n = 466), 20% CP (n = 252), and 8% FP (n = 107). FOLFOX significantly increased PFS (progression free survival) compared to CP, with a hazard ratio of 0.73 (95% CI 0.58–0.92, p = 0.009). The duration of treatment was similar across all groups. Survival outcomes among regimens were similar, but analysis revealed worse ECOG–PS (Eastern Cooperative Oncology Group–Performance Status), > 2 metastatic sites, bone metastases, hypoalbuminemia, higher NLR (neutrophil-to-lymphocyte ratio), and CP regimen as predictors of poor PFS. Fatigue was common in all treatments, with the highest incidence in FOLFOX (77%), followed by FP (72%), CAPOX (68%), and CP (60%). Other notable toxicities included neuropathy (FOLFOX 69%, CAPOX 62%), neutropenia (FOLFOX 52%, FP 55%), hand–foot syndrome in CP (46%), and thromboembolic events (FP 12%, CP 11%).ConclusionsFOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.

Pathological complete response following neoadjuvant chemotherapy for locally advanced intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Cases when found are often advanced with vascular invasion, and radical resection is often difficult. Despite curative resection, the postoperative recurrence rate of patients with histological lymph node metastasis is high, and their prognosis is poor. Therefore, there is an urgent need to establish multidisciplinary treatment that combines chemotherapy and surgical resection. The efficacy of neoadjuvant chemotherapy (NAC) for locally advanced ICC is unclear. In this report, a case of locally advanced ICC in which pathological complete response (pCR) was achieved after NAC is described.Case presentationA 79-year-old woman was admitted to a local hospital with appetite loss. Computed tomography showed a 100 × 90 mm low-contrast tumor in the left hepatic lobe and segment 1 with invasion to the inferior vena cava (IVC), and several lymph nodes along the left gastric artery and lesser curvature were enlarged. Therefore, she was treated with a combined chemotherapy regimen of gemcitabine and cisplatin. After four courses, the tumor size decreased to 30 × 60 mm without invasion to the IVC. Left hepatectomy extending to segment 1 with bile duct resection combined with middle hepatic vein resection (H1234-B-MHV), dissection of regional lymph nodes and pyloroplasty were performed. After radical resection, pCR was achieved. She is alive with no evidence of disease, 2 years after surgery.ConclusionsIn this case, a patient with locally advanced ICC achieved pCR to NAC. NAC may be effective for ICC. Patients who achieve pCR may have a better prognosis.

Clinical Predictors of Cisplatin Chemoradiation-Induced Ototoxicity in HPV-Positive Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study.

Cisplatin-based chemoradiation is a standard treatment for many patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), an etiologically distinct subset of head and neck cancer. Although associated with good long-term survival, clinical risk factors for ototoxicity have been understudied in this population. This study aimed to evaluate clinical predictors associated with ototoxicity in HPV-positive OPSCC patients treated with cisplatin chemoradiation. This retrospective case-control study included 201 adult patients (>18 years) with histologically confirmed HPV-positive OPSCC who received cisplatin chemoradiation as their primary treatment from 2001 and 2019 at a single tertiary cancer center. Ototoxicity was determined using baseline and follow-up audiometry and the Common Terminology Criteria for Adverse Events v5.0 grading criteria (Grade ≥2). Multivariable logistic regression [adjusted odds ratio (aOR)] identified significant predictors that increased the odds of ototoxicity. A total of 201 patients [165 males; median (IQR) age, 57 (11) years] were included in the study. The incidence of ototoxicity in the worst ear was 56.2%, with the greatest hearing loss occurring at high frequencies (4-8 kHz), resulting in a loss of 12.5 dB at 4 to 6 kHz and 20 dB at 6 to 8 kHz. High-dose cisplatin administration compared to weekly administration [aOR 4.93 (95% CI: 1.84-14.99), P = .003], a higher mean cochlear radiation dose [aOR 1.58 (95% CI: 1.12-2.30), P = .01], smoking history [aOR 2.89 (95% CI: 1.51-5.63), P = .001], and a 10 year increase in age [aOR 2.07 (95% CI: 1.25-3.52), P = .006] were each independently associated with increased odds of ototoxicity. Clinical predictors of ototoxicity in HPV-positive OPSCC patients treated with cisplatin-based chemoradiation include the use of a high-dose cisplatin regimen, higher cochlear radiation doses, a history of smoking, and older age. With the rising incidence of this malignancy in Western countries and overall improved survivorship, our research motivates future studies into risk stratification and earlier interventions to mitigate and reduce the risk of ototoxicity.

Outcomes of 3-year follow up with induction vs first line chemotherapy in oral cancer patients: An observational hospital-based study.

Our study aims to analyse and compare the efficacy, adverse effect profile and survival among the Paclitaxel/Cisplatin/5-Flurouracil (TPF) induction chemotherapy and Paclitaxel/carboplatin (PC) first line or cisplatin chemotherapy in a high-volume tertiary care cancer centre. 215 patients with oral cavity cancer were recruited in this study. Patients with stages I-IIc underwent surgical resection or radiation therapy 66-74 GY/fraction. Patients of Stages III-IV were administered with either induction chemotherapy TPF or PC or cisplatin regimen. Treatment responses were assessed by CT and MRI. Response rates, survival and adverse effects data were tabulated and analysed. The mean age was 49.2 ± 11.68 years. Symptoms were ulceration (33.5%), growth (20.5%), pain (13%), ulcer-proliferative growth (8.4%) and swelling (13, 6%). The tumour site was found at the base of the tongue, C01 (42.2%) followed by C06 (35.8%), C08 (6.5%), C07 (5.2%) and C05 (4.6%). There were no significant differences ( P > 0.05) in efficacy and survival outcomes between the different groups of treatment. Median survival was achieved within 36 months. The major side effect observed were anaemia (15.81%), diarrhoea (36.2%), dyspepsia (28.8%), fever (33.95%), mucositis (28.85%), myalgia (33.95%) and nausea (7.9%). Survival among the responder categories (CR, PR and NR) was significantly different as per Log-rank analysis ( P = 0.015). TPF induction therapy and PC first line chemotherapy showed similar efficacy, safety profile and survival whereas cisplatin shows poor efficacy and safety and survival in Indian oral cancer patients.

Phase I/II clinical trial of regorafenib plus durvalumab (MEDI4736) in patients with chemotherapy-refractory advanced biliary tract cancers.

TPS581 Background: Biliary tract cancers (BTC) are a heterogeneous group of cancers affecting the epithelial lining of the intra- and extrahepatic portions of the biliary tree, ranking as the second most prevalent primary liver cancer after hepatocellular carcinoma. A subgroup of BTC was found to have an abundant tumor specific neoantigen expression, enriched expression of immune related genes and genes regulating inhibitory immune checkpoint proteins. Recent advancements in BTC treatment include the TOPZ-1 trial, which established the survival advantage of adding durvalumab to the gemzar + cisplatin regimen with an estimated 24-month overall survival rate of 24.9% versus 10.4% for placebo. The hazard ratio for progression-free survival favored durvalumab at 0.75 (95% CI, 0.63 to 0.89; P=0.001). Objective response rates also showed improvement, with 26.7% for durvalumab and 18.7% for placebo. Furthermore, single agent regorafenib has exhibited efficacy in patients with refractory advanced metastatic cholangiocarcinoma, particularly in terms of progression-free survival, favoring regorafenib over placebo, the overall toxicity profile was as expected. Regorafenib targets multiple tyrosine kinases and has been reported to show immunomodulatory properties that may counteract tumor-induced immunosuppression, providing a rationale for combining it with checkpoint inhibitors. We believe that modulating the tumor microenvironment with small molecule inhibitors like regorafenib will have synergistic effect when combined with checkpoint-based immunotherapy like durvalumab in patients with chemo refractory BTC. Methods: This study comprises a single-arm, unblinded Phase I/II trial designed to assess the safety and efficacy of the combination therapy involving regorafenib and durvalumab in patients with chemo-refractory advanced BTC. The Phase I portion employed a 3 + 3 design with two dose levels of regorafenib (80 mg and 120 mg) administered in conjunction with 1500 mg IV durvalumab every 28 days. Phase I successfully completed, and the Data Monitoring Committee (DMC) endorsed the continuation of the trial as planned. Eligibility: Histologically confirmed unresectable or metastatic disease. Progressed on at least one line of therapy. May have received checkpoint inhibitor in the past. Inclusion criteria also include ECOG PS 0-1. Objectives:Primary Phase I: Safety of regorafenib in combination with durvalumab.Phase II: Progression-free survival (PFS).Secondary:Disease Control Rate (DCR), Overall response rate (ORR), Overall survival (OS). Statistical Plan: Interim futility testing after one year, halting if conditional power &lt; 20%. Final analysis: PFS and OS via Weibull Regression. Enrollment is currently ongoing with 8 out of 40 patients enrolled.

Prolonged progression-free survival achieved by gemcitabine, cisplatin, and albumin-bound paclitaxel for the treatment of advanced biliary tract cancers.

A regimen of gemcitabine, cisplatin, and nab-paclitaxel (GPA) has shown promising results in patients with advanced biliary tract cancer (aBTC). This study aimed to evaluate the benefit of GPA compared to a regimen of gemcitabine plus cisplatin (GP) in patients with aBTC. Retrospective study. Patients with aBTC who received first-line chemotherapy with GPA or GP regimen at the Samsung Medical Center between July 2020 and June 2022 were included. The primary endpoint was progression-free survival (PFS). In all, 37 patients were treated with GPA and 43 patients with GP. The GPA group showed significantly longer median PFS [12.0 months (95% CI, 7.2-16.8)] compared to the GP group [5.5 months (95% CI, 3.7-7.4; p = 0.007)]. The median overall survival (OS) was also longer in the GPA group [18.7 months (95% CI, 13.7-23.7)] than in the GP group [10.7 months (95% CI, 1.5-19.9); p = 0.021]. First-line chemotherapy with GPA was associated with longer PFS, while metastatic disease at initial diagnosis and post-treatment increase in CA 19-9 level were associated with worse PFS. The GPA regimen improved the PFS of patients with aBTC compared to the GP regimen but showed no significant benefit in terms of OS after adjusting for confounding variables. Further large-scale studies are required to establish optimal indications for GPA.

NEOADJUVANT CHEMORADIOTHERAPY IN THE MULTIMODALITY TREATMENT OF STAGE IIIA(N2) NON-SMALL CELL LUNG CANCER (NSCLC)

Summary. The choice of optimal treatment for stage IIIA(N2) non-small cell lung cancer (NSCLC) remains controversial, since the five-year survival rate of this category of patients cannot meet modern medical requirements and patient expectations even after radical surgery and chemotherapy (CT). Accordingly, the analysis of available clinical data and the search for the most effective multimodal treatment option are constantly ongoing. The main treatment strategy for stage IIIA(N2) NSCLC is surgery with induction CT. As part of a comprehensive clinical approach, neoadjuvant CT (NCT) is used to eliminate distant micrometastases, leading to increased survival in an independent operation. Meanwhile, induction with concurrent chemoradiotherapy (CRT) followed by surgery resulted in a 30% to 40% improvement in 5-year survival. Aim: to evaluate the results of treatment of patients with stage IIIA(N2) NSCLC after the use of various methods of neoadjuvant and adjuvant therapy in case of surgical intervention. Object and methods: the effect of NCRT was performed in 37 patients with stage IIIA(N2) NSCLC in selected tumors of the lungs and the middle of the National Cancer Institute. This group of patients was planned for multimodal treatment, which included 3 or 4 cycles of chemotherapy with platinum-based drugs following the regimens of cisplatin + docetaxel or carboplatin + paclitaxel with one-hour radiotherapy (RT), consisting of sessions in the or classical fractionation with a single dose of 2 Gy, SOD up to 50 Gy with subsequent surgery. The number of CT cycles (3 or 4) depended on the result of the control observation of the dynamics of regression of the tumor process. In the core of the vicoristan group, there was the first control group of stage IIIA(N2) NSCLC patients with NCT (n = 194). This group of patients was given 3 or 4 courses of CT using a regimen similar to the main group: cisplatin / carboplatin + docetaxel / paclitaxel, and in the second control group – similar to the number of courses and drugs, neoadjuvant CT and RT in SOD 50 Gy in adjuvant regimen (n = 60) with further surgical treatments. All patients, depending on the prevalence of the tumor process, underwent radical surgery in the form of lobectomy, bilobectomy or pneumonectomy with mediastinal lymphodissection. Results: median survival in the main group was 30.12 months, in the first control group (NCT) – 23.68 months and the second control group (NCT + adjuvant RT) – 23.23 months, respectively. In the main group, 5 (14.7%) patients were diagnosed with a complete morphological response of the primary tumor and a complete morphological response of the tumor tissue in the regional lymph nodes. In addition to the complete morphological response of the primary tumor and metastatic mediastinal lymph nodes (tumor cells were not detected in histological preparations), in 5 (14.7%) cases, a pronounced morphological response of a highly differentiated tumor was detected (residual viability of tumor tissue to 12±5%). These patients had a higher median survival (45 and 39 months, respectively) compared to controls. Conclusion: the treatment regimen with NCRT is more promising for increasing patient survival.

MFOLFOX-HAIC+lenvatinib+PD-1 inhibitors versus GC/GS/GEMOX chemotherapy as a first line therapy for advanced biliary tract cancer: A single-center retrospective cohort study.

Biliary tract tumors (BTC) account for about 3% of all digestive system tumors, with rising incidence and limited treatment options, particularly for advanced stages, underscoring the need for innovative therapies. This retrospective cohort study evaluated the safety and efficacy of a novel regimen combining hepatic artery infusion chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX-HAIC) alongside lenvatinib and programmed cell death protein-1 (PD-1) inhibitors (mFOLFOX-HAIC+lenvatinib+PD-1i) compared to standard regimens of gemcitabine plus cisplatin, gemcitabine plus S1, or gemcitabine plus oxaliplatin (GC/GS/GEMOX) in advanced BTC patients treated from March 2019 to November 2023. A total of 89 patients were analyzed, with 55 receiving hepatic arterial infusion chemotherapy and 34 receiving the GC/GS/GEMOX regimens. Among these, 23 patients were in the mFOLFOX-HAIC+lenvatinib+PD-1i group, while 24 were in the GC/GS/GEMOX group. The median progression-free survival (mPFS) for the mFOLFOX-HAIC+lenvatinib+PD-1i group was 15 months compared to 6 months for the GC/GS/GEMOX group. Similarly, the median overall survival (mOS) was 20 months for the mFOLFOXHAIC+lenvatinib+PD-1i group versus 13 months for the GC/GS/GEMOX group. The objective response rate (ORR) and disease control rate (DCR) for the mFOLFOX-HAIC+lenvatinib+PD-1i group were 48.5% and 87.0%, respectively, both significantly higher than those observed in the GC/GS/GEMOX group at three months of treatment. The incidence of adverse events (AEs) was similar between the mFOLFOX-HAIC+lenvatinib+PD-1i group and the GC/GS/GEMOX group, at 86.5% and 84.2%, respectively, with no statistically significant difference in complication rates. Overall, mFOLFOX-HAIC+lenvatinib+PD-1i appears to be a safe and well-tolerated treatment for advanced BTC, demonstrating superior mPFS and mOS compared to standard regimens.

Secreted Frizzled-Related Protein 4 Induces Gastric Cancer Progression and Resistance to Cisplatin and Oxaliplatin via β-Catenin Dysregulation

Introduction: Gastric cancer is the fifth most common cancer and third leading cause of cancer-related death worldwide. There are three main ways to treat gastric cancer: surgical resection, radiation therapy, and drug therapy. Furthermore, combinations of two to three regimens can improve survival. However, the survival outcomes of chemotherapy in advanced gastric cancer patients are still unsatisfactory. Unfortunately, no widely useful biomarkers have been verified to predict the efficacy of chemotherapy for locally advanced gastric cancer. Methods: An MTT assay was used to determine the cell viability after cisplatin or oxaliplatin treatment. Western blotting and immunohistochemistry were utilized to examine the secreted frizzled-related protein 4 (sFRP4) level and associated signaling pathways. Immunofluorescence staining was utilized to analyze the location of β-catenin. Colony formation and Transwell assays were used to analyze the functions related with cisplatin, oxaliplatin, and sFRP4. Results: We have found that gastric cancer patients treated with combinations of 5-fluorouracil (5-FU) and cisplatin regimens have better survival rates than those treated with 5-FU-based chemotherapy alone. sFRP4 was selected as a potential target from stringent analysis and intersection of 5-FU and cisplatin resistance-related gene sets. sFRP4 was shown to be overexpressed in clinical gastric tumor tissues and positively correlated with a worse survival rate. In addition, sFRP4 and β-catenin were upregulated in cisplatin- and oxaliplatin-resistant gastric cancer cells compared to parental cells. Immunofluorescence staining and nuclear fractionation showed that β-catenin was translocated from the cytosol into the nucleus. Moreover, sFRP4 was detected in the conditioned medium of these resistant cells, which indicates that sFRP4 might have an extracellular role in chemotherapy resistance. Increased migration capacity and dysregulation of epithelial-mesenchymal transition-related markers, which might result from the dysregulation of sFRP4, were observed in cisplatin- and oxaliplatin-resistant gastric cancer cells. Discussion/Conclusion: In summary, sFRP4 might play a critical role in resistance to cisplatin and oxaliplatin, cell metastasis, and poor prognosis in gastric cancer via the Wnt-β-catenin pathway. Investigations of the molecular mechanism underlying sFRP4-modulated cancer progression and chemotherapeutic outcomes can provide additional therapeutic strategies for gastric cancer.

ARID5B promoted the histone demethylation of SORBS2 and hampered the metastasis of ovarian cancer

Ovarian cancer (OVCA) is the 4th most common female tumor after breast cancer, cervical cancer, and endometrial cancer, and now is mainly treated with debulking surgery and postoperative cisplatin and paclitaxel-based combination chemotherapy regimens. However, OVCA is insidious in its development and recurrence occurred in some patients after treatment. It is of great significance to study the pathogenesis of ovarian cancer and identify more biomarkers. Recently, the role of histone methyltransferase (HMT) and histone demethylase (HDM) in oncogenesis and development of malignant tumors has raised attention. Unlike other JMJC demethylases that have both JMJC and ARID domains in a single molecule, PHF2 requires assembly into a complex with a DNA-binding subunit (ARID5B) and exerts its enzymatic activity. Therefore, the aim of this manuscript is to investigate the role of histone demethylases ARID5B-PHF2 complex in the metastasis of OVCA. As result, we found ARID5B and PHF2 are both low expressed in OVCA tumor tissues and cell lines and associated with diagnosis and prognosis. Also, ARID5B suppressed rearrangement of the cytoskeleton in the process of EMT in OVCA cell lines. The role of PHF2 as a tumor suppressor was also confirmed both in vivo and in vitro. SORBS2 is low expressed in OVCA tumor tissues and cell lines and associated with diagnosis and prognosis. The expression of SORBS2 is positively corelated with the expression of ARID5B and PHF2. The promoter of SORBS2 is proved combined with ARID5B. The expression of SORBS2 was increased due to ARID5B-PHF2 complex promoted the histone demethylation by mainly binding in site H3K36me2 and therefore promoting the transcription of SORBS2. In conclusion, ARID5B-PHF2 complex promoted the histone demethylation of SORBS2 by mainly bind in site H3K36me2 and therefore promote the transcription of SORBS2 then hampered the process of EMT and tumor generation of OVCA. These results provided a new perspective on the molecular mechanisms of OVCA development and offered a new target of clinical diagnose and treatment of OVCA.

Efficacy and Safety of Chemotherapy (DDGP vs VIPD) Followed Radiotherapy Vs Radiotherapy Followed Chemotherapy (DDGP vs VIPD) Vs Radiotherapy Alone for Newly Diagnosed Early Stage Extranodal Natural Killer/T Cell Lymphoma: Final Results of a Prospective, Multicenter, Randomized, Controlled Clinical Trial

Background: Extranodal Natural Killer/T Cell Lymphoma (ENKTL) is a highly aggressive form of non-Hodgkin lymphoma (NHL), primarily found in Asia and commonly linked to Epstein-Barr virus (EBV) infection. Despite the treatment efficacy for early stage ENKTL has been improved in recent years, there is no consistent approach for clinical treatment. Current guidelines includes radiotherapy (RT) alone, concurrent chemoradiation therapy (CCRT), sequential chemoradiation, and sandwich chemoradiation. Here we present the final results of the efficacy and safety of sequential therapies of DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen or VIPD (etoposide, ifosfamide, cisplatin and dexamethasone) regimen combined with RT, and RT alone. M ethods: We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of sequential chemotherapy (DDGP vs VIPD regimen) followed by RT, sequential RT followed by chemotherapy, and RT alone in eligible patients with newly diagnosed stage I/II ENKTL. Upon study entry, patients were randomized 1:1:1:1:1 to receive either DDGP regimen followed by RT (DDGP+RT), or VIPD regimen followed by RT (VIPD+RT), or RT followed by DDGP regimen (RT+DDGP), or RT followed by VIPD (RT+VIPD), or RT alone. Patients assigned to the DDGP group were administered cisplatin (20 mg/m 2, intravenous, days 1-4), dexamethasone (15 mg/m 2, intravenous, days 1-5), gemcitabine (800 mg/m 2, intravenous, on days 1 and 8), and pegaspargase (2500 IU/m 2, intramuscular, on day 1). Those in the VIPD group received etoposide (100 mg/m 2, intravenous, days 1-3), ifosfamide (1.2 g/m 2, intravenous, days 1-3), cisplatin (33 mg/m 2, intravenous, days 1-3), and dexamethasone (40mg, intravenous, days 1-4). Both the DDGP and VIPD regimens were repeated every 21 days. For the sequential chemotherapy followed by RT group, patients underwent 3 cycles of either DDGP or VIPD regimen, followed by 50 Gy (2 Gy * 25 times) of intensity modulated radiotherapy (IMRT). In the sequential RT followed by chemotherapy group, patients were first given 50 Gy (2 Gy * 25 times) of IMRT and then sequential either DDGP or VIPD regimen. Meanwhile, the RT alone group received 50 Gy (2 Gy * 25 times) of IMRT only. The primary end point of our study was progression free survival (PFS), with secondary end points including complete remission rate (CRR), objective response rate (ORR), overall survival (OS). R esults: Our study, spanning January 2011 to August 2020, involved 244 patients from 22 centers across China, with 200 randomly assigned to receive treatment (40 in each group). Both the demographic and disease characteristics of the patients at baseline were generally consistent across all treatment groups. During a median follow-up of 72.1 months, the median PFS (mPFS) was not reached in neither the DDGP + RT nor RT + DDGP groups, compared to 36.3 months in the VIPD + RT group, 78.3 months in the RT + VIPD group, and 89.6 months in the RT alone group. The 5-year PFS rates for the DDGP + RT, VIPD + RT, RT + DDGP, RT + VIPD, and RT alone groups were 81.5%, 46.1%, 79.8%, 53.1%, and 57.5% respectively. Similarly, the 10-year PFS rates were 81.5%, 42.8%, 74.1%, 45.9%, and 45.7% respectively. Compared with RT alone, PFS was improved in DDGP + RT group (p = 0.006) and RT + DDGP group (p = 0.024). Compared with VIPD + RT, PFS was improved in DDGP + RT group (p = 0.006) and RT + DDGP group (p = 0.026). Either between DDGP +RT and RT + DDGP group or between VIPD +RT and RT +VIPD group, PFS showed no differences. Median OS was not reached in 5 groups. OS showed no differences in 5 groups (p = 0.27). The patients who failed from either VIPD regimen or RT alone received DDGP regimen. This might be the reason why the OS showed no differences between 5 groups. The CRRs of 5 groups (DDGP + RT, VIPD +RT, RT + DDGP, RT +VIPD, RT alone) were 87.5%, 57.5%, 82.5%, 69.2%, and 67.5%, respectively. Similarly, the ORRs were 97.5%, 77.5%, 90.0%, 74.4%, and 87.5%, respectively. Conclusions: The DDGP regimen exhibited promising outcomes in this randomized clinical trial for newly diagnosed early-stage ENKTL patients. The sequential therapies with DDGP regimen could improve the efficacy compared with RT alone. Patients could also benefit more from therapies with DDGP regimen than those with VIPD regimen. The order in which chemotherapy and RT were applied has no fatal impact on the prognosis of early-stage ENKTL.

The efficacy and safety of 5-fluorouracil/cisplatin/vincristine as a multi-agent chemotherapy regimen in gestational trophoblastic neoplasia.

To determine the efficacy and safety of the 5-fluorouracil (5-FU), cisplatin, and vincristine (FPV) chemotherapy regimen in patients with gestational trophoblastic neoplasia (GTN). We performed a retrospective study of 96 GTN patients with International Federation of Gynecology and Obstetrics (FIGO) scores of 5 or greater in the Second Affiliated Hospital of Zhengzhou University from October 2013 to October 2019, including 54 patients who received FPV chemotherapy and 42 who received 5-FU/actinomycin D/vincristine (FAV) chemotherapy. A pulsed intravenous device was used to administer 5-FU. The clinical characteristics, adverse events, and response rates were compared between the groups. The patients in the FPV and FAV groups received a total of 228 and 190 courses of chemotherapy, respectively. Complete response (CR) was found in 88.89% (48/54) and 90.48% (38/42) of patients in the FPV group and FAV group, respectively (p = 0.801). Both chemotherapy regimens yielded CR in all low-risk patients (100% vs. 100%), whereas 86.67% and 88.24% of high-risk patients achieved CR (FPV vs. FAV, p = 0.836), respectively. The most common adverse events (AEs) were myelosuppression and gastrointestinal reactions including neutropenia (83.97%), anemia (60.05%), and nausea (46.41%). In comparison to those in the FAV group, patients in the FPV group reported higher rates of grade 1/2 nausea (53.51% vs. 37.89%, p = 0.001), hepatotoxicity (28.95% vs. 17.89%, p = 0.008), oral mucositis (23.25% vs. 10.53%, p = 0.001), and grade 3/4 neutropenia (47.37% vs. 27.37%, p < 0.001), while grade 1/2 diarrhea (7.46% vs. 13.68%, p = 0.037) and grade 3/4 oral mucositis (0 vs. 6.32%, p < 0.001) were much more common in the FAV group. The rate of overall survival at 5 years was 96.8% in the FPV group and 97.3% in the FAV group (p = 0.760), whereas the 5-year disease-free survival rates were 95.9% and 93.9% (p = 0.754), respectively. The FPV and FAV regimens with pulsed intravenous 5-FU yielded comparable CR rates and tolerability in patients with GTN with FIGO scores of >5. Further randomized controlled trials are warranted to validate their efficacy.

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

PurposeThe number of older adults with head-and-neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiotherapy is considered standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older HNSCC patients. MethodsThe XXX study is an international multicenter cohort study including older (≥65 years) HNSCC patients treated with definitive radiotherapy at 13 academic centers in the United States and Europe. Here, patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analyses, while Fine‐Gray competing risks regressions were performed regarding the incidence of locoregional failures (LRFs) and distant metastases (DMs). ResultsSix hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n=310; 44%), followed by cisplatin plus 5-fluorouracil (n=137; 20%), carboplatin (n=73; 10%), and mitomycin c plus 5-fluorouracil (n=64; 9%). Carboplatin-based regimens were associated with diminished PFS (HR=1.39 [1.03-1.89], p<0.05) and a higher incidence of LRFs (SHR=1.54 [1.00-2.38], p=.05) compared with single-agent cisplatin, whereas OS (HR=1.15 [0.80-1.65], p=.46) was comparable. There were no oncological differences between single-agent and multi-agent cisplatin regimens (all p>.05). Median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR=0.71 [0.53-0.95], p=.02), PFS (HR=0.66 [0.51-0.87], p=.003), and lower incidence of LRFs (SHR=0.50 [0.31-0.80], p=.004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR=0.996 [0.993-0.999], p=.009). ConclusionsSingle-agent cisplatin can be considered as the standard chemotherapy regimen for older HNSCC patients who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant also in older HNSCC patients. Trial RegistrationXXX