Cisplatin Infusion Research Articles

An audit to review compliance to cisplatin hydration guidelines within the royal Marsden NHS hospital

Abstract Introduction Cisplatin is a cytotoxic agent that forms the backbone of many cancer regimens.1 Cisplatin exhibits good anti-tumour activity however it can accumulate in the renal proximal tubules, leading to nephrotoxicity. It is therefore essential that adequate hydration with diuretics and fluids alongside is administered prior, during and after cisplatin infusion to promote renal perfusion.2 The local policy for intravenous hydration for cisplatin-based regimens states that adult patients are to be weighed prior to treatment and weighed again after treatment to ensure they have not developed fluid retention.3 This audit was necessary following the implementation of the new electronic prescribing system, where nurses no longer got prompted to weigh patients in the same way they did before. Aim To assess the level of compliance with current locally approved guidelines for cisplatin hydration administration since the launch of the new electronic prescribing system (EPIC). Methods Ethics approval was not required for this audit as retrospective use of anonymous data. Compiled records of 262 patients who were prescribed cisplatin-containing regimens from 17th March 2023 until 31st November 2023 were used to identify patients for inclusion in the audit. Data collection was performed retrospectively using a data collection form and a pilot study was carried out on 20 patients. A sample size of 144 patients was obtained using the Raosoft sample size calculator to achieve a 95% confidence interval with a 5% margin of error accepted.3 All data were collected by the auditor. Patients’ hospital numbers were then individually searched on EPIC to identify if weights were recorded pre- and post-administration of cisplatin. Treatment plans and medical notes on EPR were checked to identify if escalation was appropriately followed where patients gained >2 kg and, in this case to see if furosemide 20mg tablet was given. In addition, laboratory test results and structured notes were reviewed to ascertain if an increase in serum creatinine occurred and if patients were admitted to hospital as a consequence. Data was directly input into Microsoft excel for data analysis. Results The majority of cisplatin administration episodes (72%) did have the patient’s weight recorded before and after treatment. Of the remaining 28% where the weight was missing or incomplete, 4 episodes resulted in a documented AKI and 3 of these episodes were severe enough to warrant hospital admission. Discussion and conclusion The results demonstrate a lack of documentation of patient’s weights across RMH. Only 72% of patients who were administered IV cisplatin at RMH between 17th March 2023 and 31st November 2023 were recorded. This falls below the local guidance, which recommends all patients (100%) should be weighed pre- and post- cisplatin administration. Documentation is critical to ensure a clear audit trail and to enable identification pf patients who may be at higher risk of developing fluid retention. This therefore needs improvement. A limitation of the audit is the increased potential for human error due to the way data was collected. The requirement to search through all structured notes and observations flowsheet was time consuming and intensive, increasing the likelihood documentation may have been missed.

Combination Therapy of Lenvatinib and Hepatic Arterial Infusion Chemotherapy Using Cisplatin With Lipiodol and 5-Fluorouracil: A Potential Breakthrough Therapy for Unresectable Advanced Hepatocellular Carcinoma.

In 2021, the LEOPARD trial reported that the combination of lenvatinib+one-shot cisplatin infusion might contribute to improving the results of conventional advanced hepatocellular carcinoma (HCC) treatment. Thus, combination therapy with lenvatinib and catheterization has emerged as a focal point in treating advanced HCC. Conversely, the New FP regimen consists of low-dose cisplatin (CDDP) combined with 5-fluorouracil (5-FU) and lipiodol via hepatic arterial infusion chemotherapy (HAIC), with a high response rate of approximately 70%. Therefore, lenvatinib+New FP (LEN-New FP) may be a more promising treatment for HCC. Here, we report six patients who were administered LEN+New FP and achieved high therapeutic efficacy. Among them, one case had an interesting clinical course, which has been described in detail. This study included six patients who were administered 12 mg or 8 mg of lenvatinib once daily based on a body weight of ≥60 kg or <60 kg, respectively, along with 50 mg of cisplatin in 5-10 mL lipiodol, and a continuous infusion of 5-FU (1500 mg/5 days) infused every 2-4 weeks. Tumor evaluations were performed 4-8 weeks after the initiation of New FP administration and every 8-12 weeks thereafter. The median patient age was 65 years. All patients had a history of prior treatment with atezolizumab and bevacizumab and one of the factors associated with poor overall survival for New FP monotherapy, such as a maximum tumor diameter ≥7 cm and bilobular multifocal distribution. Four (67%) patients had severe vascular invasion. The best objective response and disease control rates were 83% and 100%, respectively. The best response of the target lesion was complete remission in four out of six patients. The LEN-New FP combination for advanced HCC showed a high response rate and was more effective in high-risk patients with factors associated with poor overall survival than that reported with conventional New FP monotherapy. Additionally, LEN-New FP exhibited extremely high objective response and disease control rates and was well tolerated, including in cases where it was considered second- or third-line systemic chemotherapy for advanced HCC. Thus, LEN-New FP can serve as a breakthrough therapy for advanced HCC based on appropriate case selection.

Effectiveness and feasibility of selective intra-arterial low dose of cisplatin infusion and concomitant radiotherapy for patients with advanced laryngeal cancer with impaired renal function: A retrospective cohort study.

Chemoradiation therapy with high-dose cisplatin is the standard regimen against advanced squamous cell carcinoma of the larynx (SCC-L). However, patients with renal dysfunction are ineligible for this regimen. We investigated the effectiveness and feasibility of selective intra-arterial low-dose cisplatin infusion and radiotherapy (modified [m]-RADPLAT) for patients with impaired renal function. We retrospectively reviewed the data of 77 patients with SCC-L who received m-RADPLAT. Fourteen and 63 patients had creatinine clearance (CrCl) values of 30 ≤ CrCl < 60 mL/min and ≥60 mL/min, respectively. The m-RADPLAT regimen led to no significant changes in serum creatinine or CrCl values post-treatment. The 5-year local control, overall survival, and laryngectomy-free survival rates of the CrCl < 60 and ≥60 groups were 90.0% and 90.5%, 100% and 81.8%, and 100% and 79.0%, respectively. Grade 3 or higher toxicity rates were not significantly different between the groups. The m-RADPLAT regimen yielded favorable survival rates and clinical outcomes in patients with impaired renal function.

3-Fr steerable microcatheter system via the upper limb artery in RADPLAT for right maxillary cancer

Background To evaluate the efficacy of a catheter system using a 3-Fr sheath with a steerable microcatheter through right upper limb artery access for superselective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) to treat right maxillary sinus squamous cell carcinoma (MS-SCC). Material and methods We retrospectively studied 46 sessions in eight patients treated between November 2020 and February 2023 using the catheter system briefly described below. A 3-Fr sheath was inserted into the distal radial, conventional radial, or brachial arteries. A coaxial catheter system with a 2.9-Fr steerable microcatheter and a 1.9-Fr microcatheter was advanced into the brachiocephalic artery. The right common carotid artery was selected by bending the tip of the steerable microcatheter. Coil embolization and intra-arterial cisplatin infusion after selecting each external carotid artery branch were achieved using this catheter system. Results Cisplatin infusion and coil embolization were successful in all sessions. Arterial occlusion at the sheath insertion sites was found in 29.4% (5/17) of the distal radial arteries and 33.3% (3/9) of the conventional radial arteries. No other major complications were observed during the procedure. Conclusion Using a 3-Fr catheter system with a steerable microcatheter through right upper limb artery access is a feasible method for RADPLAT in treating right MS-SCC.

A rat-based preclinical platform facilitating transcatheter hepatic arterial infusion in immunodeficient rats with liver xenografts of patient-derived pancreatic ductal adenocarcinoma

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens underwent histopathological examination. A liver-implanted PDAC PDX rat model was established in all 63 rats, with first CT identifying all tumors. Four weeks post-treatment, arterial infusion groups exhibited significantly smaller tumor volumes than controls for all three tumors on second CT. Xenograft tumors histologically maintained adenocarcinoma features compared to original patient tumors. Ki67 expression was significantly lower in arterial infusion groups than in the other two for the three tumors, indicating reduced tumor growth in PDX rats. A liver-implanted PDAC PDX rat model was established as a rat-based preclinical platform. Arterial cisplatin infusion chemotherapy represents a potential therapy for PDAC liver metastasis.

Use of Sodium Thiosulfate as an Otoprotectant in Patients With Cancer Treated With Platinum Compounds: A Review of the Literature.

Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL). A comprehensive narrative review is presented. Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting. Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.

QIM24-181: Joining Forces to Minimize Hypomagnesemia in Patients Receiving Cisplatin and Cetuximab Infusions.

QIM24-181: Joining Forces to Minimize Hypomagnesemia in Patients Receiving Cisplatin and Cetuximab Infusions.

Abstract 6903: Treatment efficacy of transcatheter hepatic arterial infusion chemotherapy with cisplatin in a severe immunodeficient rat model with patient-derived primary pancreatic ductal adenocarcinoma xenografted into the liver

Abstract Purpose: Liver metastases of pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease; most patients die within 5 years. There is a critical need to identify appropriate anticancer treatments for these patients. A patient-derived tumor xenograft (PDX) model in severe immunodeficient rat with primary PDAC xenografted into the liver is suitable for evaluating transcatheter hepatic arterial infusion chemotherapy. Materials and Methods: The purpose of this study was to develop a severe immunodeficient rat model with patient-derived primary PDAC xenografted into the liver, and to assess the treatment efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived tumors of PDAC were transplanted into the liver of 21 rats each, totaling 63 rats. Four weeks after transplantation, the 21 rats were randomly assigned into three treatment groups of seven rats each: hepatic arterial infusion, systemic venous infusion, and control group. Tumor volumes were evaluated on CT twice at pre-treatment and 4-weeks post-treatment. Following euthanasia of the rats, resected tumor specimens were pathologically analyzed. Results: The liver-implanted PDAC PDX rat model was established in all 63 rats. hepatic arterial infusion chemotherapy and systemic venous infusion chemotherapy with cisplatin were able to be performed in the assigned rats. The hepatic arterial infusion group significantly inhibited tumor growth and reduced Ki67 expression, indicating lower cell proliferation, compared to the control group in three PDX tumors. Conclusion: A rat-based preclinical platform was established by liver-implanted PDAC PDX rat model. Arterial cisplatin infusion chemotherapy would be one of potential therapies for PDAC liver metastases. Citation Format: Ken Kageyama, Akira Yamamoto, Masanori Ozaki, Kenjiro Kimura, Shinpei Eguchi, Ryota Tanaka, Mizue Terai, Takami Sato, Yukio Miki. Treatment efficacy of transcatheter hepatic arterial infusion chemotherapy with cisplatin in a severe immunodeficient rat model with patient-derived primary pancreatic ductal adenocarcinoma xenografted into the liver [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6903.

Prevention of cisplatin-induced hearing loss in children: achievements and challenges for evidence-based implementation of sodium Thiosulfate.

Ototoxicity is a devastating direct, irreversible side effect of platinum use in children with cancer, with its consequent effect on speech, language and social development, quality of life and adult productivity. Cisplatin, an essential chemotherapeutic agent for the treatment of solid tumors in children, is a DNA cross-linking agent. Which causes hearing loss in 50-70% of cisplatin treated children. Fortunately, to prevent hearing loss, sodium thiosulfate (STS), which binds to cisplatin, and reduces the superoxides in both tumor and outer hair cells of the cochlea has now been discovered to be an effective and safe otoprotectant if administered correctly. The aim of this perspective paper is to explore the key safety issues and challenges important for pediatric oncologists and pharmacists when considering the clinical use of STS as an otoprotectant for children and adolescents receiving cisplatin. These include: the choice of the formulation; the timing, both that of the STS in relation to cisplatin as well as the timing of the cisplatin infusion itself; the dosing; the challenge left by the definition of localized versus disseminated disease and the difference in indication for STS, between cisplatin treated patients and those receiving another platinum chemotherapeutic agent, carboplatin.

Dose-Finding and Efficacy Confirmation Trial of the Superselective Intra-arterial Infusion of Cisplatin and Concomitant Radiation Therapy for Locally Advanced Maxillary Sinus Cancer (JCOG1212): Results of the Efficacy Confirmation Phase in Patients with T4aN0M0

Background: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment. But this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas (MS-SCC). We herein report the results of the efficacy confirmation phase in the T4a cohort.Patients and methods: Patients received cisplatin 100 mg/m2 intra-arterially weekly for 7 weeks with concomitant radiotherapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (3yr OS), comparing RADPLAT with the historical control for 3yr OS in surgery (80%).Results: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 males and 11 females with a median age of 64 years (range, 40-78 years) and ECOG PS 0/1 (58/7). After excluding one ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3yr-OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (≥ grade 3), neutropenia (≥ grade 3), increased creatinine (≥ grade 2), hearing impairment (≥ grade 2), and stroke (≥ grade 2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported.Conclusion: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 MS-SCCs compared with the historical control for 3yr OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients.

The superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is effective for metastatic lymph nodes in head and neck squamous cell carcinoma.

Superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is a very promising treatment modality for locally advanced head and neck squamous cell carcinoma. However, there are some concerns regarding its potential for the control of neck lymph node metastasis. The objective of this study was to investigate whether RADPLAT provided inferior regional control compared to intravenous chemoradiotherapy (IV-CRT). A total of 172 patients with neck lymph node metastases, 66 of whom underwent RADPLAT and 106 IV-CRT, were enrolled in this study. We retrospectively compared regional control rates between RADPLAT and IV-CRT. Furthermore, to adjust for differences in factors related to patient background between the groups, we conducted inverse probability weighting (IPW) analysis using the propensity score. A comparison between the two groups revealed that the regional control rates were almost equal under unadjusted conditions; however, after adjustment by IPW analysis, the RADPLAT group had a relatively better regional control rate than did the IV-CRT group (1year regional control rate: 86.6% vs. 79.4%). In addition, the analysis of relative risk factors for regional control in the RADPLAT group showed that the absence of intra-arterial cisplatin infusion into metastatic lymph nodes was the only independent risk factor (Hazard ratio: 4.23, p = 0.04). This study showed that the regional control rate in patients treated with RADPLAT was noninferior to that for IV-CRT. Locally advanced head and neck cancers is a good indication for RADPLAT, even if the patients have neck lymph node metastases.

CRES3T: A single-arm confirmatory trial of S-1 plus cisplatin with concurrent radical-dose radiotherapy followed by surgery for superior sulcus tumor.

8514 Background: A multicenter, single-arm, confirmatory trial (CRES3T) was conducted to investigate the efficacy and safety of S-1 plus cisplatin and concurrent radical-dose thoracic radiotherapy (TRT) followed by surgery in patients with superior sulcus tumor (SST). To date, no clinical trials on radical-dose TRT in the induction setting for SST have been conducted. Methods: SST was defined as a tumor that directly invades the chest wall including the first rib or more cephalad, subclavian artery, or subclavian vein according to CT or MRI scans. Eligible patients were 20 to 75 years old and had pathologically proven non-small cell lung cancer, performance status of 0–1, and no history of prior treatment. The patients received induction therapy consisting of three cycles of S-1 plus cisplatin with concurrent TRT (66 Gy in 33 fractions) followed by surgery. S-1 was administered orally at 40 mg/m2 twice per day, on days 1–14 along with an intravenous infusion of cisplatin (60 mg/m2) on day 1. The treatment cycles were repeated every four weeks. The primary endpoint was the 3-year overall survival (OS) rate, and key secondary endpoints included progression-free survival (PFS) rate, objective response rate (ORR), pathological complete remission (pCR) rate, and toxicity. Results: Between June 2014 and March 2019, 61 patients registered and received induction therapy. Pathological diagnoses were 30 adenocarcinoma, 20 squamous cell carcinoma, and 11 others. Radiologically diagnosed tumor invasion sites were the chest wall (n=57), subclavian artery (n=18), and subclavian vein (n=10). One patient with distant metastasis that manifested after starting induction therapy was removed from this study. Forty-nine patients underwent lobectomy and resection of the involved sites. The complete resection rate was 98% (48/49). Median follow-up time was 54 months. The 3-year OS and PFS rates were 73% (95% CI: 60–83%) and 53% (95% CI: 40–65%), respectively. The ORR and pCR rate were 42% (25/60, 95% CI: 29–54%) and 33% (16/49, 95% CI: 20–46%), respectively. Grade (G) 3 or 4 toxicities during induction therapy included neutropenia (28%), anemia (13%), thrombocytopenia (5%), and hyponatremia (8%). Two (3%) cases of pneumonia resulted in death. G3 surgical complications such as supraventricular arrhythmia, chylothorax, pleural effusion, pneumonia, mediastinitis, wound infection, and arm neuropathy developed in one (2%) patient each. One (2%) cardiac arrest on postoperative day 3 resulted in death. Conclusions: CRES3T demonstrated that induction therapy using S-1 plus cisplatin and concurrent radical-dose TRT followed by surgery was safe and effective in treating SST. Therefore, this strategy is potentially a new standard treatment for SST. (UMIN: 000014386, jRCT: s031180401.). Clinical trial information: UMIN000014386 .

Ligation of the ethmoid arteries in superselective intra‐arterial infusion of cisplatin for advanced maxillary sinus cancer fed by the ophthalmic artery

Superselective cisplatin (CDDP) infusion via the external carotid artery system and concomitant radiotherapy (RADPLAT) provides favorable oncological and functional outcomes in patients with maxillary sinus cancer. However, targeted lesions are occasionally fed by the branch of the internal carotid artery. In RADPLAT for maxillary sinus cancer partly fed by the ophthalmic artery, the ethmoid arteries were ligated in two patients without medial orbital wall involvement. In four patients with that, CDDP was administered via the ophthalmic artery. A complete response was obtained in all six patients. Locoregional recurrence was not observed in any cases. However, visual acuity was lost in four patients who received the ophthalmic artery infusion. Ligation of the ethmoid arteries is recommended in RADPLAT for maxillary sinus cancer with lesions fed by the ophthalmic artery. CDDP administered via the ophthalmic artery may be considered if a patient accepts the possibility of visual loss.

Sodium thiosulfate as cisplatin otoprotectant in children: The challenge of when to use it.

Sodium thiosulfate as cisplatin otoprotectant in children: The challenge of when to use it.

Metabolomic identification of predictive and early biomarkers of cisplatin-induced acute kidney injury in adult head and neck cancer patients.

Cisplatin causes acute kidney injury (AKI) in approximately one third of patients. Serum creatinine and urinary output are poor markers of cisplatin-induced AKI. Metabolomics was utilized to identify predictive or early diagnostic biomarkers of cisplatin-induced AKI. Thirty-one adult head and neck cancer patients receiving cisplatin (dose ≥70 mg/m2) were recruited for metabolomics analysis. Urine and serum samples were collected prior to cisplatin (pre), 24-48 h after cisplatin (24-48 h) and 5-14 days (post) after cisplatin. Based on serum creatinine concentrations measured at the post timepoint, 11/31 patients were classified with clinical AKI. Untargeted metabolomics was performed using liquid chromatography-mass spectrometry (LC-MS). Metabolic discrimination was observed between "AKI" patients and "no AKI" patients at all timepoints. Urinary glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid and suberate were significantly different between AKI patients and no AKI patients prior to cisplatin infusion. Urinary glycine and hippuric acid sulfate were lower (-2.22-fold and -8.85-fold), whereas 3-hydroxydecanedioc acid and suberate were higher (3.62-fold and 1.91-fold) in AKI patients relative to no AKI patients. Several urine and serum metabolites were found to be altered 24-48 h following cisplatin infusion, particularly metabolites involved with mitochondrial energetics. We propose glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid and suberate as predictive biomarkers of predisposition to cisplatin-induced AKI. Metabolites indicative of mitochondrial dysfunction may serve as early markers of subclinical AKI.

New Regimen of Combining Hepatic Arterial Infusion Chemotherapy and Lipiodol Embolization in Treating Hepatocellular Carcinoma with Main Portal Vein Invasion.

The prognosis of HCC patients with main portal vein invasion (Vp4) is poor. We retrospectively reviewed the therapeutic outcomes with our new HAIC regimen in treating Vp4 HCC patients. Seventy-one patients received the new regimen of combining HAIC (daily infusion of cisplatin (10 mg/m2), mitomycin-C (2 mg/m2) and Leucovorin (15 mg/m2) plus 100 mg/m2 of 5-fluorouracil (5-FU) using an infusion pump for 5 consecutive days) with Lipiodol embolization between 2002 and 2018. Twenty-two patients (31.0%) also received sorafenib. The Kaplan-Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS). The OS of patients with or without additional sorafenib use or extrahepatic spread (EHS) was also compared. Fifty-six patients (78.9%) had Child-Pugh A liver function. The mean maximal tumor size was 10.3 cm. Twenty patients (28.2%) had EHS at their initial diagnosis. The objective response rate according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and median OS were 64.8% and 13 months. The 1-, 2- and 3-year survival rates were 53.1%, 21.5% and 18.7%, respectively. In the subgroup analysis, there were no significant survival difference between patients with HAIC only vs. HAIC plus sorafenib (14 vs. 13 months) and between patients with vs. without EHS (12 vs. 13 months). Our new HAIC regimen is effective in treating Vp4 HCC patients. Additional sorafenib use with our new HAIC regimen provided no survival benefit.

Rh-endostatin plus camrelizumab and chemotherapy in first-line treatment of advanced non-small cell lung cancer: A multicenter retrospective study.

Clinical evidence of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced non-small cell lung cancer (NSCLC) was limited. Recombinant human endostatin (rh-endostatin), an antiangiogenic drug, and camrelizumab, an anti-PD-1 antibody, have been approved for the treatment of advanced NSCLC in China. This study aimed to investigate the efficacy and safety of rh-endostatin plus camrelizumab and chemotherapy in the treatment of advanced NSCLC. Eligible patients were enrolled and received camrelizumab (200 mg, day 1) every 3 weeks and continuous intravenous infusion of rh-endostatin (70 mg/day, days 1-3) and cisplatin combined with pemetrexed (for adenocarcinoma) or paclitaxel (for NSCLC other than adenocarcinoma) every 3 weeks. Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. Overall, 27 patients were included, and 25 patients were eligible for efficacy evaluation. For these 25 patients, ORR was 48.15% (13/27) and DCR was 85.19% (23/27). With a median follow-up of 10.37 months, the median PFS was 8.9 (95% CI: 4.23-13.57) months. Median OS was not reached. Overall, 96.3% of patients experienced at least one treatment-related adverse event, and grade 3 TRAEs occurred in 9 (33.3%) patients. No unexpected AEs were observed. Rh-endostatin plus camrelizumab and chemotherapy showed favorable efficacy and safety profile in patients with advanced NSCLC, representing a promising treatment regimen for these patients.

Effect of SMTP-7 on Cisplatin-Induced Nephrotoxicity in Mice.

SMTP-7, a fungal metabolite, is reported to have a high degree of availability for the ischemia-reperfusion (IR)-induced acute kidney injury (AKI) model. Cisplatin, a widely used anticancer drug, has serious side effects, such as AKI. Hence, we aimed to examine the effect of SMTP-7 on cisplatin-induced AKI in this study. Significant increases in blood urea nitrogen (BUN) and serum creatinine (Scr) were observed at 72 h after the intravenous infusion of cisplatin (20 mg/kg). Histologically, necrosis and dilatation (hyaline casts) as well as regeneration were observed in proximal tubules. SMTP-7 inhibited the elevation on BUN and Scr caused by cisplatin dose dependently. The efficacy of SMTP-7 was notable when the drug was administered on the day after cisplatin treatment, whereas the repeated administration of the drug did not result in an enhanced efficacy. Moreover, 10 mg/kg of SMTP-7 considerably ameliorated tubular necrosis and dilatation. The cisplatin treatment also caused an up-regulation of tumor necrosis factor-α (TNF-α) mRNA expression prior to the elevation of the levels of BUN and Scr. Administration of SMTP-7 (10 mg/kg) at 24 h after the cisplatin infusion alleviated the up-regulation of TNF-α mRNA expression. These findings suggest that SMTP-7 exhibits a renoprotective effect against cisplatin infusion based on the inhibition of the expression of pro-inflammatory cytokines such as TNF-α and may be expected a new effective drug for the treatment of cisplatin-induced AKI.

Guillain-Barré-Like Syndrome From Esophageal Squamous Cell Carcinoma

Guillain-Barré-like syndrome (GBS) has been noted in solid tumors such as hepatocellular carcinoma, gastric, breast, and colon cancer and is characterized by an ascending weakness generally with mild paresthesias; however, it has not been noted in esophageal squamous cell carcinoma. A 64-year-old woman with moderately differentiated squamous cell carcinoma of the upper esophagus receiving 5-fluorouracil and cisplatin chemotherapy concurrently with radiation therapy presented for two weeks of progressive lower extremity weakness and numbness. She experienced acute worsening of symptoms after her cisplatin infusion. She underwent a lumbar puncture that revealed findings consistent with GBS and she began treatment with intravenous immunoglobin. She had gradual improvement in her weakness and paresthesias and was discharged to an inpatient rehabilitation facility. This case documents the first noted association between GBS and esophageal squamous cell carcinoma.

Dose-finding and efficacy confirmation trial of the superselective intra-arterial infusion of cisplatin and concomitant radiotherapy for locally advanced maxillary sinus cancer (JCOG1212): Results of the efficacy confirmation phase in the T4a cohort.

6014 Background: The JCOG1212 trial seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (RADPLAT) for patients (pts) with T4aN0M0 or T4bN0M0 maxillary sinus squamous cell carcinomas (MS-SCC). T4aN0M0 MS-SCC requires radical surgery with or without complete resection of the orbital contents as a standard treatment, which results in disfigurement and functional impairment. We herein report the results of the efficacy confirmation phase in the T4a cohort. Methods: Eligible pts with T4aN0M0 MS-SCC were registered and received cisplatin 100 mg/m 2 intra-arterially weekly for 7 weeks with concomitant radiotherapy (total 70 Gy) as determined by the results of the previous dose-finding phase. The trial investigated the 3-year overall survival (3yr OS) of RADPLAT to demonstrate its non-inferiority to surgery, the current standard of care, and its superiority to IV-CRT, which is used for pts refusing surgery. From the results of observational study undertaken by our group, the historical control for the 3yr OS was set at 80% for surgery and 65% for IV-CRT. A margin of 15% was set to demonstrate its non-inferiority to surgery and superiority to IV-CRT. Thus, when the lower boundary of the two-sided 90% confidence interval (CI) exceeds the threshold of 65% for 3yr OS, RADPLAT will be confirmed as the new standard. A sample size of 62 was required to achieve 80% power with a one-sided 5% significance level. Results: From April 2014 to August 2018, 65 pts were registered in the T4a cohort from 18 institutions, consisting of 54 males and 11 females with a median age of 64 years (range, 40-78 years) and ECOG PS 0/1 (58/7). After the exclusion of one ineligible patient, 64 pts were included in the primary analysis of efficacy and safety. The complete clinical remission rate was 73.4% (47/64, 95% CI, 60.9%-83.7%), with 15 showing CR and 32 showing good PR. The median follow-up was 4.5 years in all eligible pts and the primary endpoint for 3yr-OS was 82.8% (90% CI, 73.4%-89.2%), which met the prespecified hypothesis. The 3yr event-free survival and 3yr local event-free survival were 60.9% (95% CI, 47.9%-71.7%) and 65.6 % (95% CI, 52.5%-75.8%), respectively. With regard to acute adverse events, neutropenia (≥ grade 3), increased creatinine (≥ grade 2), hearing impairment (≥ grade 2), mucositis (≥ grade 3), and stroke (≥ grade 2) were observed in 14.1%, 3.1%, 3.1%, 20.3%, and 1.6% of pts, respectively. One treatment-related death due to a thromboembolic event was reported. Conclusions: RADPLAT is non-inferior to surgery and superior to IV-CRT for pts with T4aN0M0 MS-SCCs and showed manageable toxicities. Therefore, RADPLAT, as well as surgery, should be considered the new standard treatment option for these pts. Clinical trial information: UMIN000013706.