Effect of the area under the curve of carboplatin dosage on therapeutic efficacy and safety in Chinese patients with epithelial ovarian cancer / 西安交通大学学报(医学版)

【Objective】 To retrospectively analyze the average carboplatin dosage and calculate the area under the curve (AUC) using the Calvert formula in first-line chemotherapy in patients with epithelial ovarian cancer in The First Affiliated Hospital of Xi’an Jiaotong University so as to evaluate the effect of the AUC difference in the Chinese population on therapeutic efficacy and safety. 【Methods】 We enrolled patients who underwent first-line chemotherapy with paclitaxel and carboplatin 3-week regimen in our hospital from January 1, 2012 to January 1, 2022. According to the median of AUC, the patients were divided into high-dose group and low-dose group. The overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) were compared. 【Results】 A total of 153 patients were enrolled in this study and the median AUC of carboplatin was 3.981 (range 2.314-5.446). Only 10.46% patients (16/153) had an AUC above 5. There were 77 patients with the AUC0.05). The ORR in the low-dose group and the high-dose group was 59.74% and 57.89%, respectively, and the DCR was 87.01% and 85.53%, respectively. The median PFS of the two groups was 14 and 15.5 months, respectively, and the median OS was 50 and 55 months, respectively. None of the above outcomes were statistically different between the two groups (P>0.05). The two groups showed significant differences in the incidence of anemia, neutropenia, and thrombocytopenia (P<0.05). The incidence of nausea and vomiting, grade 1-2 diarrhea or constipation, and grade 1-2 fever showed significant differences (P<0.05). In addition, the incidence of dose limiting toxicity (DLT), including grade 4 thrombocytopenia and febrile neutropenia (FN), was significantly increased in the high-dose group (P<0.05). 【Conclusion】 Compared with the recommended AUC 5-6 of carboplatin abroad, the actual carboplatin dosage in the first-line chemotherapy for patients with epithelial ovarian cancer was generally insufficient in our hospital. There was no difference in therapeutic efficacy between the patients with AUC<4 and AUC≥4. However, considering the increased risk of some AEs and DLT in the high-dose group, it is not recommended to increase the carboplatin AUC blindly.

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients / 医学前沿

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade ⩾ 3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.

Dose-escalation trial of lobaplatin weekly plus concurrent radiotherapy for local-regionally advanced nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To define the maximum-tolerated dose (MTD) of lobaplatin (LBP) in a weekly regimen combined with concurrent radiotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC).Methods A total of 18 cases with stage Ⅲ/Ⅳ A NPC were enrolled.Concurrent chemoradiotherapy was given to all the patients with a dose escalation of LBP.The initial dose of LBP was 15 mg/m2 with an escalating dose of 5 mg/m2.At least 3 patients were assigned into each group.Patients were proceeded into the next dose group if no dose-limiting toxicity (DLT) occurred until the MTD was achieved.Efficacy and toxicity were evaluated regularly.Results Three patients were assigned into the 10 mg/m2,3 into the 15 mg/m2,and 6 into the 20 mg/m2 and 25 mg/m2 groups,respectively.Two patients experienced DLT in the 25 mg/m2 group.Hence,the MTD was determined as 20 mg/m2.At 3 months after corresponding treatment,the remission rate of nasopharyngeal tumors and neck-positive lymph nodes of the patients was 100％.The most common toxicity was reversible bone marrow suppression.Conclusions The MTD of weekly lobaplatin plus concurrent IMRT is 20 mg/m2 for locally advanced NPC.This regimen is reliable and safe,which is worthy of further clinical study.

Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints. RESULTS: A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8). CONCLUSION: OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.

A phase Ⅰ study of postoperative concurrent radiotherapy and oral doxifluridine and leucovorin for Ⅱ/Ⅲ stage rectal cancer / 中华放射肿瘤学杂志

Objective A phase Ⅰ study was conducted to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity(DLT) of chemotherapy of oral doxifluridine(5-dFUR) and leucovorin with concurrent standard radiotherapy(RT) as adjuvant treatment in patients with rectal cancer. Methods Patients aged 18-75 years old, Karnofsky scored ≥70%, stage Ⅱ/Ⅲ rectal cancer after curative surgery were eligible. Total RT dose was delivered as DT 50 Gy in the fraction of 2.0 Gy per day for 5 weeks to the pelvic area. 5-dFUR was administered concurrently with radiotherapy in escalating doses, and oral leucovorin was The DLTs included grade 3 or grade 4 hematologic and nonhematologic toxicity. Results From Aug. 2005 the most common side effects although all neutropenia was less grade 3. The DLT was observed in 1 patient of RT. In the following 3 enrolled patients, one suffered grade 3 abdominal cramp pain, diarrhea, fatigue, nausea/vomit and grade 2 neutropinea and fever. Grade 3 diarrhea was also observed in all the additional 3 papatients didn't complete the scheduled concurrent chemoradiotherapy due to severe side effects,including 1 at grade 3 abdominal cramp pain,fatigue and nausea/vomit. Conclusions Diarrhea is the most common and severe side effect in this phase Ⅰ study. The MTD of doxifluridine, concurrently with RT and fixed dose of oral cramp pain is often accompanied with diarrhea and nauser/vomit when the dose of doxifluridine exceeds 550 mg/( m2 · d) or 900 mg/d,patients need to be observed carefully.

Phase I Clinical Trial of Paclitaxel Plus Ifosfamide for the Patients with Refractory Ovarian Cancer / 대한암학회지

PURPOSE: Patients with advanced ovarian carcinoma and refractory to platinum based chemotherapy have a very poor prognosis and effective salvage regimens are needed. This study was conducted in order to determine the maximum tolerated dose (MTD) and dose limiting toxicity of combination with paclitaxel and ifosfamide. MATERIALS AND METHODS: After premedication, patients received paclitaxel (110~225 mg/m2) as a 24 hour IV infusion on day 1. Ifosfamide (1,000~1,500 mg/m2) was given as a 12 hour IV infusion with standard dose of mesna on day 2~6. All patients received G-CSF (granulocyte colony stimulating factor) on day 6~15. RESULTS: 12 patients with advanced ovarian cancer entered this trial. Toxicity included bone marrow suppression, neuromuscular toxicity, urothelial toxicity, gastrointestinal toxicity, which occurred in 84.6%, 65.3%, 30.7%, 88.4% of cycles. CONCLUSION: Neuromuscular toxicity was dose limiting toxicity. Maximum tolerated dose in com bination with paclitaxel and ifosfamide was 175 mg/m2 of paclitaxel and 1,500 mg/m2 of ifosfamide.