Tumor Response and Symptom Palliation from RAINBOW,a Phase III Trial of Ramucirumab Plus Paclitaxel in Previously Treated Advanced Gastric Cancer

BackgroundIn the intent‐to‐treat (ITT) population of the RAINBOW study, objective response rate (ORR) was 28% and 16% in the ramucirumab and control arms, respectively. To further characterize tumor response, we present details on timing and extent of tumor shrinkage, as well as associations with symptom palliation.Materials and MethodsTumor response was assessed with RECIST v1.1, and quality of life (QoL) was assessed with the European Organization for Research and Treatment of Cancer Quality‐of‐Life Questionnaire‐Core 30 (EORTC QLQ‐C30) v3.0. Prespecified and post hoc analyses were conducted in the ITT population, patients with measurable disease, or responders, and included best overall response (BOR), ORR, disease control rate (DCR), duration of response, time to response (TtR), change in tumor size, and associations of QoL with tumor shrinkage and BOR.ResultsIn both treatment arms, median TtR was 1.5 months. Responses were more durable in the ramucirumab versus control arm (median 4.4 vs. 2.8 months). In patients with measurable disease (78% of ITT), ORR was 36% versus 20%; DCR was 81% versus 61% in the ramucirumab versus control arms. Waterfall plots demonstrated more tumor shrinkage in the ramucirumab versus control arm. Regardless of treatment, tumor response and stable disease were associated with improved or stable QoL, with more tumor shrinkage associated with greater symptom palliation.ConclusionTreatment with ramucirumab plus paclitaxel yielded the highest ORR reported to date for patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. Additional details demonstrate robustness of tumor response results. The extent of tumor shrinkage is directly associated with symptom palliation and should be considered when evaluating patient needs and treatment selection. Clinical trial identification number. {"type":"clinical-trial","attrs":{"text":"NCT01170663","term_id":"NCT01170663"}}NCT01170663.Implications for PracticeRamucirumab plus paclitaxel is a recognized standard of care as it improves survival for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have been previously treated with recommended first‐line therapy. These additional data on tumor response demonstrate a positive association between tumor shrinkage and symptom palliation in a patient population that is often symptomatic. These observations included patients with nonmeasurable disease, a group of patients often underrepresented in clinical trials. This knowledge can inform treatment decisions, which align individual patient characteristics and needs with demonstrated benefits.     

Neutrophil Count and the Inflammation-based Glasgow Prognostic Score Predict Survival in Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy

Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors andthe extent these markers improve prognostic classification for patients with inoperable advanced or metastaticgastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemicinflammatory factors such as circulating white blood cell count and its components as well as that combined toform inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio(NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariateand multivariate analyses were performed to examine the impact of inflammatory markers on overall survival(OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count,a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well aselevated NLR/PLR , GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstratedthat only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independentpredictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and highGPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated withfirst-line chemotherapy. Upon validation of these data in independent studies, stratification of patients usingthese markers in future clinical trials is recommended.     

Apatinib in Combination with S-1 as First-Line Treatment in Patients with Advanced Metastatic Gastric Cancer: Results from an Open,Exploratory, Single-Arm,Phase II Trial

Lessons Learned

• Apatinib combined with S‐1 was not superior to other chemotherapy regimens as first‐line therapy for advanced gastric cancer.
• There was a tendency for patients with lymph node metastasis to have prolonged median progression‐free survival and median overall survival, compared with patients with liver metastasis.

BackgroundThe best choice of first‐line chemotherapy regimen for patients with metastatic gastric cancer is still debated. We combined apatinib and S‐1 as a new first‐line therapy to treat advanced gastric cancer. The efficacy and safety of the combination were assessed, with the goal of determining the most appropriate subgroup of patients who could benefit from this new regimen.MethodsThis study was an open, exploratory single‐arm, phase II trial. Enrolled patients received apatinib plus S‐1 treatment (apatinib, 500 mg, once a day [qd], days 1–21; S‐1, 40 mg/m², bid, days 1–14). The primary endpoints were progression‐free survival (PFS) and safety of this new regimen. Next‐generation sequencing was used to explore potential biomarkers.ResultsA total of 30 patients were enrolled. The median progression‐free survival (mPFS) was 4.21 months (95% confidence interval [CI], 2.29–6.13 months). The median overall survival (mOS) was 7.49 months (95% CI, 4.81–10.17 months). Patients with lymph node metastasis had prolonged mPFS and mOS when compared with those with liver metastasis (mPFS, 4.21 vs. 1.84 months; mOS, 8.21 vs. 6.31 months, p = .08). The most common grade 3 to 4 adverse events were abdominal pain, dizziness, and diarrhea. Gene mutation profiles between the two subgroups were significantly different.ConclusionApatinib combined with S‐1 was not superior to other chemotherapy regimens as first‐line therapy for advanced gastric cancer. Toxicity was consistent with known profiles when given as monotherapy. There was a tendency toward prolonged mPFS and mOS in patients with lymph node metastasis compared with patients with liver metastasis, which could support the need to design a future clinical trial with a better defined patient population.     

Effectiveness of Trastuzumab in Routine Clinical Practice: A Population-based Study of Patients with HER-2-positive Oesophageal,Gastroesophageal and Gastric Cancer

AimsIn the pivotal Trastuzumab for Gastric Cancer (ToGA) trial, trastuzumab improved median survival in patients with advanced HER-2-positive gastric and gastroesophageal cancer from 11.1 to 13.8 months; however, its effectiveness in routine clinical practice has not been evaluated. Our objective was to evaluate the uptake and outcomes of trastuzumab in a population-based cohort of patients with oesophageal, gastroesophageal and gastric cancer in Ontario, Canada.Materials and methodsThe Ontario Cancer Registry and linked treatment records were used to identify all patients with oesophageal, gastroesophageal and gastric cancer treated with trastuzumab during 2012–2017. Outcomes were analysed from the time of first trastuzumab cycle and included a primary outcome (survival) and secondary outcomes (uptake, delivery, 30-day hospital admission and 30-day mortality). Trends over the study period and survival were evaluated.ResultsIn total, 476 patients with oesophageal, gastroesophageal and gastric cancer received trastuzumab during the study period. The mean age was 62 years, 78% (370/476) were male, and 65% (312/476) had gastric cancer. The annual number of patients receiving trastuzumab increased over the study period (53 in 2012 and 101 in 2017). The median number of cycles of trastuzumab delivered was six. Thirty-day hospital admission and mortality rates were 17% and 4%, respectively. The median overall survival was 282 days (9.3 months).ConclusionsThe median survival of patients treated with trastuzumab for advanced oesophageal, gastroesophageal and gastric cancer in routine practice is substantially less than that observed in the pivotal clinical trial. Studies of comparative effectiveness using real-world data offer insight into outcomes achieved in routine practice.     

Chronological Changes in Neutrophil/lymphocyte Ratio in Advanced Gastric Cancer Patients Treated with Nivolumab: a Report of Nine Cases

Background: Nivolumab has been approved for use in advanced gastric cancer (GC) after third-line chemotherapy in Japan. However, it remains difficult to predict favorable nivolumab response before treatment. Methods: We evaluated the clinical course with a focus on the chronological changes in neutrophil/lymphocyte ratio (NLR) throughout the chemotherapy and assessed the relationship between nivolumab response and chronological changes in NLR before nivolumab administration. Results: We experienced nine cases who received nivolumab monotherapy for unresectable advanced or postoperative recurrent GC. Nivolumab was used as third-line chemotherapy in all patients, and partial response (PR) and stable disease (SD) were observed in two patients each. Nivolumab treatment resulted in progressive disease (PD) in five patients. In patients with PR or SD, changes in the NLR tended to correspond to the response of target metastatic lymph nodes to first- and second-line chemotherapy. In the four cases with PR or SD following nivolumab, ∆NLRresponses that was the difference in the degree of decline during the most effective pretreatment chemotherapy were 1.39, 0.73, 1.62, and 1.22. However, the patients with PD showed lower ∆NLRresponses, at 0.66, 0.66, 0.25, 0.13, and -0.05 in the five cases. Mean ∆NLRresponses in the patients with PR or SD and patients with PD were 1.17 and 0.33, respectively (P = 0.0008). Conclusions: We experienced nine GC cases treated with nivolumab and assessed the association between chronological NLR changes throughout chemotherapy and tumor response to nivolumab. Changes in NLR during pretreatment chemotherapy might predict tumor response to nivolumab monotherapy in patients with advanced GC.     

胃癌患者血清以及癌组织中LDH的表达及其与患者预后的相关性

目的 探讨乳酸脱氢酶(LDH)在胃癌患者血清、癌组织中的表达以及与患者预后的相关性.方法 选取80例术中经病理确诊为胃癌的患者作为本次研究的对象,另选取同期进行体检的健康人80例作为对照组.采用全自动生化分析仪检测2组对象血清中LDH水平.术中取胃癌组织、癌旁正常组织及癌旁淋巴结组织,采用免疫组织化学法对3处组织中的LDH表达情况进行分析.采用Spearman秩相关分析LDH在胃癌患者血清及癌组织中的表达情况及其与临床病理特征及预后的相关性.结果 胃癌患者、正常人血清中LDH水平分别为(349.41±97.23)IU/ml、(185.40±52.24) IU/ml,胃癌患者血清中LDH含量明显多于对照组正常人(P ＜0.05).胃癌组织中LDH含量最高,明显高于癌旁正常组织、癌旁淋巴组织中LDH的含量.Spearman秩相关分析显示,胃癌患者血清中LDH含量与淋巴结转移、TNM分期、侵袭情况、分化程度等因素相关(P＜0.05),癌组织中LDH阳性表达与年龄、淋巴结转移、侵袭情况、分化程度等密切相关(P＜0.05).结论 LDH在胃癌患者血清及癌组织中的表达显著高于正常人及癌旁正常组织,且血清LDH及癌组织中LDH的表达均与淋巴结转移、侵袭情况、分化程度等因素密切相关,可作为评估胃癌患者预后的辅助指标.     

A Modified Epirubicin and Oxaliplatin Plus Capecitabine (EOX) Regimen as a Second- Line Therapy in Patients with Advanced Gastric Cancer

Objective: We aimed to evaluate the effectiveness of an mEOX (modified epirubicin, oxaliplatin plus capecitabine) regimen as second line therapy after failure of mDCF (modified docetaxel, cisplatin plus fluorouracil). Methods: Gastic cancer patients for whom first-line therapy was unsuccessful and who subsequently received mEOX (epirubicin 50 mg/ m2 on day 1, oxaliplatin 85 mg/m² day 1 and capecitabine twice-daily dose of 625 mg/ m2, p.o. for 2 weeks) every 3 weeks until disease progression or unacceptable toxicity, were retrospectively analyzed. Results: The study population comprised 129 cases with a median age of 55 years (range= 27-78), the majority being male (76 %). Most (75.2%) had ≥ 2 sites of metastasis. The median number of chemotherapy courses was five (range= 2–9). Forty-nine achieved a partial response and 33 showed stable disease, resulting in a ORR (overall response rate) of 38% and a DCR (disease control rate) of 63.6%. The most frequent features of grade 3-4 hematological and non-hematological toxicity were neutropenia (8.5%) and nausea/vomiting (5.4%). None of the patients suffered death due to toxicity. The median PFS was 4.7 months (95% CI, 4.1–5.3) and the OS was 7.4 months (95% CI, 6.3–8.5). On multivariate analysis, age ≥ 60 years and ECOG performance status (0-1) were independent prognostic factors affecting PFS and OS. Conslusions: In advanced gastric cancer patients, who progress after first line chemotherapy and have an ECOG performance status of 0-1, mEOX is a well tolerated triple regimen associated with a promising OS and PFS.     

血清CEA、CA125及Cyfra21-1水平对中晚期非小细胞肺癌患者预后的影响

目的 探讨晚期非小细胞肺癌（NSCLC） 患者血清癌胚抗原（CEA） 、糖类抗原（CA125）、非小细胞肺癌相关抗原（Cyfra21-1）水平与无疾病进展生存期的相关性。方法 选取2012年6月至2014年5月于宜昌市第二人民医院确诊的非小细胞肺癌患者120例,对其临床资料进行回顾性分析,了解CEA、CA125、Cyfra21-1水平与无疾病进展生存期的相关性。结果 与鳞癌患者相比,血清CEA水平在肺腺癌患者中明显升高（P＜0.05）;血清CA125水平在Ⅳ期肺腺癌患者中明显升高（P＜0.05）;血清Cyfra21-1在患者疾病一般特征中差异未见统计学意义（P＞0.05）。血清CEA、CA125、Cyfra21-1水平升高的患者中位无疾病进展生存期分别为4.2、4.5、4.3月,与正常组相比差异均有统计学意义（P＜0.05）。结论 晚期非小细胞肺癌患者CEA、CA125、Cyfra21-1升高与无疾病进展生存期存在明显的相关性,临床医师可通过检测患者血清CEA、CA125、Cyfra21-1水平判断预后。     

胃癌患者外周血中CEA mRNA的检测及其临床意义

目的 探讨胃癌思者外周血中CEAmRNA表达的临床意义。方法 采用巢式RT—PCR法，检测42例胃癌患者外周血中的CEAmRNA表达情况。采用化学发光法检测血清中CEA水平。以胃腺癌细胞株SGC—7如l作为阳性对照，以20例正常人外周血作为阴性对照。结果 42例胃癌患者CEAmRNA阳性率为45．2％(19／42)，其中25例行根治术的胃癌患者肿瘤切除术后血CEAmRNA阳性率明显高于术前(56．0％V．s28．0％，P＝0．039)。胃癌患者外周血中CEAmRNA表达与肝转移相关，但与血清CEA值、肿瘤部位、UICC分期及分化程度无关。胃腺癌细胞株SGC—790l中CEAmRNA均呈阳性表达；20例正常人外周血中CEAmRNA均呈阴性表达。结论 胃癌患者外周血中CEAmRNA表达可作为癌细胞血道播散的标志，对判断其预后及指导临床治疗具有重要意义。胃癌手术中应采用“不接触技术”以减少术中癌细胞播散。     

Phase II Study of Ramucirumab Plus Irinotecan Combination Therapy as Second-Line Treatment in Patients with Advanced Gastric Cancer: HGCSG1603

BackgroundRamucirumab is a human IgG1 monoclonal vascular endothelial growth factor receptor-2 antibody that inhibits tumor cell growth and affects the tumor cell microenvironment. We assessed the efficacy and safety of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with previously treated advanced gastric cancer.Materials and MethodsPatients with advanced gastric cancer refractory or intolerant to primary chemotherapy were included. Ramucirumab 8 mg/kg plus irinotecan 150 mg/m² combination therapy was administered every 2 weeks. The primary endpoint was progression-free survival rate at 6 months and secondary endpoints were overall survival, progression-free survival, response rate, safety, and dose intensity for each drug.ResultsThirty-five patients were enrolled between January 2018 and September 2019. The progression-free survival rate at 6 months was 26.5% [95%CI, 13.2%–41.8%, P = .1353)]. Median progression-free and overall survivals were 4.2 months (95%CI, 2.5-5.4 months) and 9.6 months (95%CI, 6.4-16.6 months), respectively. The overall response rate was 25.9% (95%CI, 11.1-36.3%) and disease control rate was 85.2% (95%CI, 66.3-95.8%). Grade ≥3 adverse events that occurred in >10% of patients included neutropenia, leucopenia, anemia, anorexia, and febrile neutropenia. No death or new safety signals with a causal relation to the study treatment were observed.ConclusionAlthough the primary endpoint was not achieved statistically, combination therapy of ramucirumab plus irinotecan showed anticancer activity and a manageable safety profile for second-line treatment of patients with advanced gastric cancer.     

血清CA125、CEA、IL-10水平检测对晚期非小细胞肺癌患者预后价值分析

目的 探讨晚期非小细胞肺癌患者血清CA125、CEA、IL-10水平在预后中的价值.方法 采用ELISA法检测不同分期NSCLC患者治疗前后CA125、CEA、IL-10的水平;观察对比化疗前后不同分期的NSCLC患者CA125、CEA、IL-10的表达水平;评价化疗后NSCLC患者的疗效及生存期.结果 化疗前Ⅳ期患者CA125、CEA、IL-10水平高于Ⅲ期患者;PR患者血清CA125、CEA、IL-10水平治疗后明显降低,SD患者CA125、CEA、IL-10水平治疗前后无显著变化,PD患者CA125、CEA、IL-10水平治疗后均显著升高;PR患者平均生存期显著长于SD患者,SD患者平均生存期显著长于PD患者.结论 血清CA125、CEA、IL-10是评估晚期非小细胞肺癌患者预后有价值的指标.     

Inflammatory Ratios as Predictors for Tumor Invasiveness,Metastasis, Resectability and Early Postoperative Evolution in Gastric Cancer

Our study aimed to evaluate the baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in relation to invasion, metastasis, and resectability for patients with gastric cancer, respectively, as predictors of death during hospitalization or surgical complications. A retrospective cohort study was conducted on 657 gastric cancer subjects. Inflammatory biomarkers were computed. The associations with tumor stage, metastasis, optimal procedure, in-hospital mortality, and surgical complications were evaluated. Subjects who underwent curative-intent surgery presented lower median NLRs (2.9 vs. 3.79), PLRs (166.15 vs. 196.76), and SIIs (783.61 vs. 1122.25), and higher LMRs (3.34 vs. 2.9) than those who underwent palliative surgery. Significantly higher NLRs (3.3 vs. 2.64), PLRs (179.68 vs. 141.83), and SIIs (920.01 vs. 612.93) were observed for those with T3- and T4-stage cancer, in comparison with those with T1- and T2-stage cancer. Values were significantly higher in the case of metastasis for the NLR (3.96 vs. 2.93), PLR (205.22 vs. 167.17), and SII (1179 vs. 788.37) and significantly lower for the LMR (2.74 vs. 3.35). After the intervention, the NLR, PLR, and SII values were higher (p < 0.01) for patients with surgical complications, and the NLR and SII values were higher for those who died during hospitalization. Higher NLRs, PLRs, SIIs, and lower LMRs were associated with a more aggressive tumor; during early follow-up, these were related to post-operative complications and death during hospitalization.     

Efficacy and Safety of Docetaxel or Epirubicin,Combinedwith Cisplatin and Fluorouracil, (DCF and ECF) Regimens as First Line Chemotherapy for Advanced Gastric Cancer: a Retrospective Analysis from Turkey

Objectives: Advanced gastric cancer (AGC) patients have a poor prognosis. The best benefit of chemotherapy is usually achieved by first line setting. Very few studies have compared combination regimens. This study was designed to compare two combination regimens. Methods: Patients with advanced gastric cancer receiving first line chemotherapy were retrospectively collected, and divided into two groups, receiving DCF (docetaxel, cisplatin and fluorouracil) or ECF (epirubicin, cisplatin and fluorouracil) regimens. Data were collected for theretrospective analysis in a single center. Results: Eighty-six patients were eligible for analysis. Median overall survival (OS) was 10.0 months in the ECF group and 11.0 months in the DCF group (p=0.31). Median progression free survival (PFS) for ECF and DCF was equal at 6.0 months. Second line chemotherapy were administered in more than one third of patients. Both regimens had similar toxicity. Conclusions: This is the first study investigating the outcomes of gastric cancer chemotherapy in this region. ECF and DCF regimens have similar efficacy and a similar tolerability profile for first line treatment of advanced gastric cancer. The decision of the first line chemotherapy in advanced gastric cancer could be improved with patient selection according to clinical parameters and molecular markers.     

Limited Efficacy of Cisplatin,UFT and Hydroxyurea Treatment in a Retrospective Evaluation of Patients with Metastatic Gastric Cancer

Background: Most gastric cancer cases are diagnosed at advanced stage and the prognosis is therefore poor.Combination chemotherapy regimens like FAM, FAMTX, ECF, ELF are recommended in advanced gastriccancer. Of particular interest is the HLFP protocol (hydroxyurea, leucovorin, 5-FU, cisplatin) which is reportedto give good response rates. In the present study we evaluated the efficacy of oral UFT instead of 5-FU andleucovorin. Methods: We retrospectively evaluated the efficacy of cisplatin, UFT, and hydroxyurea in combinationin 14 patients with metastatic gastric cancer. Patients with brain metastasis were excluded. The doses of agentswere: oral hydroxyurea 1.5 g/day on days 1-3; cisplatin 80 mg/m2 infusion on day 1 for two hours; and UFTcapsule 400 mg/day dose on days 1 to 14. Results: The results were progressive disease in 8 (57%) patients,stable disease in 2 (17%) patients and partial response in 1 (7%) patient. The overall survival was 7.9 months (3-15), progression free survival was 3.4 (1-7) months. Conclusions: Due to high toxicity and low response rates,cisplatin, UFT and hydroxyurea combination demonstrated limited activity against gastric cancer and was notfound to be effective for the treatment of advanced gastric cancer.     

Validation of a Dietary Inflammatory Index (DII) and Association with Risk of Gastric Cancer: a Case-Control Study

Background: Gastric cancer (GC) is the fifth most common malignancy and the second leading cause of cancerrelateddeaths worldwide. Studies have shown that dietary components and inflammation are implicated in the etiologyof GC. Methods: We examined the ability of a dietary inflammatory index (DII) to predict the odds of GC in a casecontrolstudy conducted from December 2014 to May 2016. The subjects were 82 cases and 95 controls who attendedspecialized centers in Tabriz, Iran. DII scores were computed from a validated 168-item food frequency questionnaire.Logistic regression models were used to estimate odds ratios (ORs) adjusted for age, sex, body mass index, education,smoking, alcohol, H.pylori infection, physical activity, aspirin/NSAID use and total caloric intake. Results: In the fullyadjusted model, subjects with a DII score >-1.77 had nearly 3.5 times higher odds of having GC compared with subjectswith DII≤-1.77, (ORDII>-1.77≤-1.77=3.39; 95%CI=1.59, 7.22). Also, for every one-unit increase in DII, there was acorresponding increase in hs-C-reactive protein, tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1b: β=0.09, 0.16,0.16 and 0.10, respectively; and a corresponding decrease in IL-10: β=-0.11. Conclusion: Subjects who consumed a morepro-inflammatory diet were at increased odds of GC compared to those who consumed a more anti-inflammatory diet.     

A Single-arm Phase II Study Combining NLG207, a Nanoparticle Camptothecin,with Enzalutamide in Advanced Metastatic Castration-resistant Prostate Cancer Post-Enzalutamide

BackgroundDespite the clinical efficacy of enzalutamide monotherapy in patients with advanced prostate cancer, therapeutic resistance and disease progression are inevitable. We proposed a study to evaluate NLG207, a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor camptothecin, in combination with enzalutamide, in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on enzalutamide.MethodsThis was a single-arm, optimal two-stage, phase II study to evaluate the efficacy of NLG207 in combination with enzalutamide in patients with mCRPC who received prior enzalutamide. A lead-in dose escalation evaluated the recommended phase 2 dose of NLG207 in combination with enzalutamide. Patients received NLG207 via IV infusion every 2 weeks and enzalutamide 160 mg orally once daily.ResultsBetween March 2019 and June 2021, four patients were accrued to the lead-in dose escalation. Two of the four patients were evaluable and both experienced DLTs at the NLG207 12 mg/m² dose level; one DLT was related to a dose delay for noninfective cystitis and myelosuppression, the other a grade 3 noninfective cystitis. Further evaluation of NLG207 in combination with enzalutamide was halted and the study was ultimately terminated. PSA declines from baseline were observed in two patients.ConclusionNLG207 12 mg/m² in combination with enzalutamide was not well tolerated in patients with mCRPC following several lines of the standard of care therapy.ClinicalTrials.gov Identifier{"type":"clinical-trial","attrs":{"text":"NCT03531827","term_id":"NCT03531827"}}NCT03531827.