Clinical tolerability and pharmacokinetics of troxacitabine / 中华肿瘤杂志

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

Impact of Cytoreductive Nephrectomy on Survival in Patients with Metastatic Renal Cell Carcinoma Treated by Targeted Therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The metastatic renal cell carcinoma (mRCC) patients treated with upfront cytoreductive nephrectomy combined with α-interferon yields additional overall survival (OS) benefits. It is unclear whether mRCC patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) will benefit from such cytoreductive nephrectomy either. The aim of the study was to identify variables for selection of patients who would benefit from upfront cytoreductive nephrectomy for mRCC treated with VEGFR-TKI.</p><p><b>METHODS</b>Clinical data on 74 patients enrolled in 5 clinical trials conducted in Cancer Hospital (Institute), Chinese Academy of Medical Sciences from January 2006 to January 2014 were reviewed retrospectively. The survival analysis was performed by the Kaplan-Meier method. Comparisons between patient groups were performed by Chi-square test. A Cox regression model was adopted for analysis of multiple factors affecting survival, with a significance level of α = 0.05.</p><p><b>RESULTS</b>Fifty-one patients underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 23 patients were treated with targeted therapy alone (noncytoreductive nephrectomy group). The median OS was 32.2 months and 23.0 months in cytoreductive nephrectomy and noncytoreductive nephrectomy groups, respectively (P = 0.041). Age ≤45 years (P = 0.002), a low or high body mass index (BMI <19 or >30 kg/m2) (P = 0.008), a serum lactate dehydrogenase (LDH) concentration >1.5 × upper limit of normal (P = 0.025), a serum calcium concentration >10 mg/ml (P = 0.034), and 3 or more metastatic sites (P = 0.023) were independent preoperative risk factors for survival. The patients only with 0-2 risk factors benefited from upfront cytoreductive nephrectomy in terms of OS when compared with the patients treated with targeted therapy alone (40.0 months vs. 23.2 months, P = 0.042), while those with more than 2 risk factors did not.</p><p><b>CONCLUSIONS</b>Five risk factors (age, BMI, LDH, serum calcium, and number of metastatic sites) seemed to be helpful for selecting patients who would benefit from undergoing upfront cytoreductive nephrectomy.</p>

An open-labeled, randomized, multicenter phase IIa study of gambogic acid injection for advanced malignant tumors / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gambogic acid is a pure active compound isolated from the traditional Chinese medicinal plant gamboge (Garcinia morella Desv.). Based on the preliminary results of a phase I study, this phase IIa study compared the efficacy and safety of different dosage schedules of gambogic acid in patients with advanced malignant tumors.</p><p><b>METHODS</b>Patients with advanced or metastases cancer who had not received any effective routine conventional treatment or who had failed to respond to the existing conventional treatment were randomly assigned to receive either 45 mg/m(2) gambogic acid intravenously from Days 1 to 5 of a 2-week cycle (Group A), or 45 mg/m(2) every other day for a total of five times during a 2-week cycle (Group B). The primary endpoint was objective response rate (ORR).</p><p><b>RESULTS</b>Twenty-one patients assigned to Group A and 26 to Group B were included in the final analysis. The ORRs were 14.3% in Group A and 0% in Group B. It was not possible to analyze the significant difference because one of the values was zero. The disease control rates (DCRs) were 76.2% in Group A and 61.5% in Group B (P = 0.0456). The observed adverse reactions were mostly Grades I and II, and occurred in most patients after administration of the trial drug. There was no significant difference in the incidence of adverse reactions between the two arms.</p><p><b>CONCLUSIONS</b>The preliminary results of this phase IIa exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m(2). The DCR was greater in patients receiving gambogic acid on Days 1 - 5 of a 2-week cycle, but the incidence of adverse reactions was similar irrespective of the administration schedule.</p>

Factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the clinical factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer.</p><p><b>METHODS</b>Clinical data were retrospective analyzed to determine the clinical factors affecting the outcome of 166 patients with advanced non-small cell lung cancer who received EGFR-TKI treatment in our hospttal from January of 2005 to December of 2006.</p><p><b>RESULTS</b>One hundred and nineteen patients benefited from EGFR-TKI treatment in the total of 166 patients and the disease control rate was 71.7%. Among the factors analyzed, sex, age, smoking, pathological type, brain and bone metastasis or not when EGFR-TKI was used, the time using EGFR-TKI and the level of LDH at the time of diagnosis had no significant effect on the clinical benefit rate. Among the 126 patients with serum CEA assayed at diagnosis, 84 cases had a higher serum CEA level. Compared with the patients with normal serum CEA level, the patients with a higher serum CEA level benefited more easily from EGFR-TKI therapy, with a disease control rate of 79.8% and 59.5%, respectively (P = 0.016). Among the patients who got benefits from EGFR-TKI treatment, smoking and the CEA level at diagnosis had effects on the duration of progression-free survival. The progression free survivals were 9.57 ± 6.75 months in non-smokers, 4.86 ± 3.44 months in light-smokers and 5.25 ± 4.34 months in heavy-smokers (P = 0.007). The progression free survival was 9.45 ± 7.48 months in the group with a higher serum CEA level and 6.52 ± 4.46 months in the group with normal serum CEA level (P = 0.036).</p><p><b>CONCLUSIONS</b>In patients with advanced non-small cell lung cancer, EGFR-TKIs treatment is safe and effective. The patients with high CEA level are prone to benefit from it.</p>

Phase II clinical study on the modified DCF regimen for treatment of advanced gastric carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A phase III trial involving docetaxel, cisplatin, and fluorouracil (DCF) in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but with a high rate of hematologic toxicity. To reduce toxicity while maintaining the efficacy of DCF, we reduced the doses of docetaxel (D) and cis-platinum (CDDP), and administered 5-fluorouracil (5-FU) via a continuous intravenous (CIV) infusion.</p><p><b>METHODS</b>Chemotherapy-naive patients with gastric adenocarcinomas received D (60 mg/m(2) 1 hour on day 1), CDDP (30 mg/m(2) on days 1 and 2), and 5-FU (1500 mg×m(-2)×24 h(-1) CIV on days 1 and 8 every 3 weeks). The primary endpoint was the response rate.</p><p><b>RESULTS</b>Fourteen patients were enrolled. Based on the efficacy evaluation following at least 2 cycles of treatment, there was 7.1% complete remission (CR), 71% partial remission (PR), 14% stable disease (NC/SD), and 7.1% progressive disease (PD). The median survival time was 13 months. Nine patients (64%) had grade III-IV neutropenia, and 4 patients (29%) had grade IV neutropenia, among whom 1 had grade IV neutropenia with grade III nausea and vomiting.</p><p><b>CONCLUSION</b>The modified DCF regimen is highly active and has a favorable toxicity profile in Chinese patients with gastric cancer.</p>