Evaluation of efficacy and safety of modified infusion of fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) in treatment of metastatic colorectal cancer: A retrospective study of 21 cases / 解放军医学杂志

Objective To evaluate the safety and preliminary efficacy of mFOLFOXIRI (the combination of irinotecan, oxaliplatin and 5-fluorouracil with reducing dosages) in first-line treatment for Chinese patients with unresectable metastatic colorectal cancer (mCRC). Methods A total of 21 patients received mFOLFOXIRI treatment: irinotecan 150mg/m2 on day 1, oxaliplatin 85mg/m2 on day 1, leucovorin 200mg/m2 on day 1, and 5-fluorouracil (5-FU) 2800mg/m2 in a 48-h continuous infusion starting on day 1. The regimen was repeated every 2 weeks. Result All the 21 patients were evaluated for efficacy of the aforesaid therapeutic regimen, and the incidence of toxic effects. No death occurred in association with the treatment. The total rate of grade 3 to 4 adverse events was 42.9% (9/21) including 38.1% (8 cases) with grade 3 neutropenia and 4.8% (1 case) suffering from grade 3 anemia. One of 21 patients (4.8%) showed grade 4 neutropenia accompanied by fever. The delivered relative dose intensity of irinotecan, oxaliplatin and 5-FU during the entire treatment course were 93.4%, 98.5% and 97.6%, respectively of planned dosage. In the intention-to-treat analysis for treatment activity, 14 patients showed remission, 6 stability, and 1 with progression of the disease. The overall response rate was 66.7%, and the disease control rate was 95.2%. Three patients (15.8%) with residual liver metastases were radically resected after mFOLFOXIRI chemotherapy. Conclusions This mFOLFOXIRI project has manageable toxicity and is well tolerated in Chinese patients. The safety profile appears to be improved compared with standard FOLFOXIRI regimen. In addition, the antitumor activity and preliminary efficacy seem to be maintained.

Efficacy and Safety of Tenofovir and Lamivudine in Combination with Efavirenz in Patients Co-infected with Human Immunodeficiency Virus and Hepatitis B Virus in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV.</p><p><b>METHODS</b>One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.</p><p><b>RESULTS</b>Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1·1.73 m-2) to week 12 (104 ml·min-1·1.73 m-2) but was almost back to baseline at week 48 (111 ml·min-1·1.73 m-2).</p><p><b>CONCLUSION</b>This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.</p>

Correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer (CRC).</p><p><b>METHODS</b>Clinical data of CRC patients treated with irinotecan-based chemotherapy in the Peking University Cancer Hospital between January 1996 and December 2011 were collected, and their blood samples were collected accordingly. Genomic DNA was extracted from blood samples. The following SNP detection of MDR1 and ABCG2 genes was conducted by direct sequencing method. The correlation of genetic SNPs with efficacy and toxicity of irinotecan treatment was further analyzed.</p><p><b>RESULTS</b>Allele frequencies of MDR1 2677 G>T/A, ABCG2 421 C>A, 34 G>A, 376 C>T were comparable with previous studies. Genetic SNPs results from peripheral blood samples and tumor tissues were highly consistent. Patients carrying MDR1 2677 wild type had higher clinical benefit than those carrying mutant genotype, while the differences were not significant. The progression-free survival (PFS) was longer in wild-type patients as compared to mutant-type patients in second-line chemotherapy (P=0.012). There were no significant correlations between ABCG2 421 C>A, 34 G>A, 376 C>T and chemotherapy efficacy. No significant correlations were observed between MDR1 2677 G>T/A, ABCG2 421 C>A, ABCG2 34 G>A, ABCG2 376 C>T and irinotecan-related grade 3 and 4 neutropenia or diarrhea.</p><p><b>CONCLUSION</b>MDR1 2677 G>T/A may be served as a biomarker in predicting the efficacy of irinotecan chemotherapy in patients with colorectal cancer.</p>

Optimization of stent-balloon system based on surrogate modeling technique / 医用生物力学

Objective To make the stent expand uniformly along the axial, an improved kriging optimization algorithm is applied for to the optimal design of stent-balloon system to find the optimal length of the balloon. Methods Based on finite element method results, kriging surrogate model combining with Latin hypercube sampling (LHS) approach and expected improvement (EI) function was employed for the optimization of balloon length to reduce stent dog-boning effect during its dilation. Results The kriging surrogate model could approximately establish the relationship between stent dog-boning rate and balloon length and so to replace the expensive reanalysis of stent dilation. Sample points from LHS could perfectly represent the vector space. EI function could be used to effectively find out the global optimal solution with high probability. The optimal length of balloon could make the stent expand uniformly. Conclusions This adaptive optimization method based on kriging surrogate model can optimize the design of stent–balloon system effectively.

Analysis of stent expansion, blood flow and fatigue life based on finite element method / 医用生物力学

Objective To study the expansion behavior of stent in stenotic vascular, in stent blood flow and fatigue life of stent by finite element method. Methods ANSYS was used to simulate the expansion of stent in stenotic vascular. The blood flow model was created by constructing the entities based on deformation of the related nodes from the result of dilation process. A sample model was also built to simulate the in stent blood flow. Stent fatigue life was evaluated based on Goodman’s method and accumulated damage method, respectively. Results (1) Plastic deformation appeared on most parts of struts. The major stresses were localized in the corner of the slots. (2) Turbulent flow occured near the stent. Stresses of stent in cross section of bridge struts along the direction of blood flow were highest. (3) Goodman’s method showed that the stent was safe, and cumulative damage indicated that the largest cumulative damage occured in the second cross section of bridge struts. Conclusions Finite element method can be effectively used to simulate the stent expansion, in stent blood flow and stent fatigue life.

Fatigue life optimization for coronary stent under the effect of blood flow / 医用生物力学

Objective To evaluate the fatigue life of coronary stent under the effect of blood flow and thus optimize the stent design.MethodsA simplified model of the stent, blood, plaque and artery was established using Pro/Engineering, and the periodic blood flow impact on the vascular stent was simulated by finite element method via ANSYS. The result on hemodynamics from such stent was then used to evaluate its fatigue life. The geometric parameters of the stent were chosen as design variables for optimization. By using Latin Hypercubic sampling and ANSYS program, responses of the sample points could be obtained and the Kriging surrogate model was then constructed to optimize the fatigue life of the coronary stent.Results Goodman’s method showed that the optimized stent was safe. The cumulative damage method indicated that the largest damage occurred at the second cross-section of the bridge struts. The fatigue life of the optimized stent could be enhanced by 30.55%. Conclusions The finite element method can be used to evaluate the fatigue life of the coronary stent, and the optimization of stent by establishing Kriging model can effectively enhance the fatigue life of the stent.

Therapeutic effect of combined cisplatin and docetaxel vs fluorouracil regimen with concurrent radiotherapy on advanced esophageal carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the therapeutic effect and adverse effects of two regimens, namely cisplatin and docetaxel (DC) regimen and fluorouracil (PF) regimen, both with concurrent radiotherapy, in the treatment of advanced esophageal squamous cancer.</p><p><b>METHODS</b>Forty-eight patients with esophageal squamous cancer were randomly assigned in DC regimen and PF regimen groups. All the patients received conventional radiotherapy at a total dose of 60 Gy (in 30 fractions) for 6 weeks. In DC regimen group, the patients received intravenous infusion of docetaxel (75 mg/m(2)) for 1 h on day 1 and DDP (25 mg/m(2) daily) on days 1-3, with every 28 days as one cycle. PF regimen consisted of cisplatin (25 mg/m(2)) on days 1-3 and continuous intravenous infusion of fluorouracil (500 mg/m(2)) for 5 days, with every 28 days as one cycle. All the patients were suggested to have no less than 2 cycles.</p><p><b>RESULTS</b>The 3-year median survival time in DC regimen was slightly longer than that in PF regimen group (26 vs 23 months, Χ2=3.4041, P=0.065). The same result was also found in the short-term effect and adverse reactions including ?myelosuppression and gastrointestinal reactions. Only the adverse reaction of radiotherapy-induced esophagitis showed a significant difference between the two groups (P=0.049).</p><p><b>CONCLUSION</b>DC regimen with synchronous radiotherapy is effective and safe for treating advanced esophageal squamous cancer.</p>

Combined chemotherapy with cisplatin, docetaxel and capecitabine for metastatic nasopharyngeal carcinoma: a retrospective analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and toxicity of the combined chemotherapy with docetaxel, capecitabine and cisplatin (TXP) in the treatment of metastatic nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>This retrospective analysis involved 22 patients with metastatic NPC receiving treatment with the TXP regimen. The patients were given docetaxel at 60 mg/m² on day 1, cisplatin at 20 mg/m² on days 1-3, and capecitabine at 1 250 mg/m² on days 1-14, and the treatment cycle was repeated ever 3 weeks.</p><p><b>RESULTS</b>Of the 22 patients, 14 (63%) achieved partial remission, 2 (9%) had complete remission, and 5 (23%) showed stable disease. The overall clinical response rate of the patients was 72% with a 1-year survival rate of 68%, median progression-free survival of 8 months, and overall survival of 14 months. The main toxicity was myelosuppression; 7 (32%) patients experienced grade 3/4 neutropenia, and 5 (23%) had grade 3/4 anemia. All the other adverse effects were tolerable and reversible.</p><p><b>CONCLUSION</b>The TXP regimen is safe and effective for treatment of metastatic NPC, and the results are comparable with those of the reports in recent literatures.</p>

Three-dimensional conformal radiotherapy combined with stereotactic radiotherapy for locally advanced non-small cell lung cancer: efficacy and complications / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the therapeutic efficacy of three-dimensional conformal radiotherapy (3DCRT) combined with stereotactic radiotherapy (SRT) and the radiation-induced complications in patients with locally advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Sixty-eight patients with locally advanced NSCLC were randomly divided into two groups. The 33 patients in groups A received 3DCRT at the total dose of 66 to 70 Gy in 33 to 35 fractions, and the 35 patents in group B received stereotactic radiotherapy (SRT) at the dose of 20 Gy in 4 fractions (500 cGy per fraction every other day) after 60 Gy 3DCRT.</p><p><b>RESULTS</b>The total response rates in groups A and B were 56.3% and 80.0%, with the complete remission rates of 9.4% and 28.6%, respectively, both showing significant differences between the two groups (P<0.05). The 1- and 2-year survival rates of the patients in group A were 65.6% and 46.8%, respectively, which were comparable to those in group B (74.3% and 51.4%, respectively, P>0.05). The median survival time in groups A and B were 12.6 and 18.3 months, respectively. The major radiation-induced complications in the two groups included grade I to II acute radiation esophagitis and hematopoietic toxicity. The complications in later stages following the radiation were grade I to II radiation lung fibrosis, occurring at a similar incidence between the two groups.</p><p><b>CONCLUSION</b>The combination of 3DCRT and SRT produces better therapeutic effects than 3DCRT alone in patients with locally advanced NSCLC.</p>