Efficacy of neoadjuvant chemotherpy in patients with locally advanced gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of neoadjuvant chemotherapy in patients with locally advanced gastric cancer, and to analyze the relevant factors of recurrent death of gastric cancer after adjuvant chemotherapy.</p><p><b>METHODS</b>Clinical data of 49 patients who underwent neoadjuvant chemotherapy for locally advanced gastric cancer between July 2007 and June 2011 were reviewed. Preoperative staging was determined by endoscopic ultrasonography and abdominal computer tomography (CT) or magnetic resonance imaging (MRI). Chemotherapy was administered for regimen of two or three drugs. Prognostic factors were analyzed by univariate and multivariate analysis with Cox proportional hazard model.</p><p><b>RESULTS</b>The response rate was 33.3% (16/48) and disease control rate was 93.8% (45/48). Forty-four (89.8%, 44/49) patients received curative resection after neoadjuvant chemotherapy, among whom 90.9% (40/44) underwent D2 lymphadenctomy. Thirty-two cases had pathological response and 2 patients had pathological complete response. The average hospital stay was 11.6 days and 2 patients had longer hospitalization because of postoperative pancreatic complications. The toxicities were most in grade 1-2. All the patients were followed up postoperatively and the median follow-up was 21.6 months. Median progression-free survival was 29.6 (95%CI:24.0-35.2) months and median overall survival was 34.6 months (95%CI:29.8-39.4). Imaging response (P=0.038, RR=0.168, 95%CI:0.031-0.904) and pathological response (P=0.007, RR=0.203, 95%CI:0.064-0.642) were identified as independent prognostic factors with COX multivariate analysis.</p><p><b>CONCLUSIONS</b>Neoadjuvant chemotherapy has quite high disease control rate and R0 resecting rate for patients with locally advanced gastric cancer. Imaging response and pathological response are most important prognostic factors in those patients.</p>

Efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer, mCRC / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer (mCRC).</p><p><b>METHODS</b>Seventy-seven mCRC patients received BEV plus 5-Fu type, oxaliplatin or irinotecan-based chemotherapy. The clinical efficacy and bevacizumab-related adverse reactions were observed. The efficacy assessment was conducted after at least 2 cycles of BEV therapy. The adverse reactions were recorded in each therapy cycle. Among the 77 cases, 64 patients had finished the efficacy assessment. The adverse reactions in all patients were assessed.</p><p><b>RESULTS</b>The overall response rate (ORR) of BEV plus chemotherapy regimen was 18.75% (12/64), and the disease control rate (DCR) was 75.0% (48/64). In 27 patients who received the regimen as first-line treatment, the ORR reached 37.0% (10/27), while the DCR was 85.2%. Four patients with potentially resectable lesions became resectable after the regimen and received R0 resection of the liver metastases successfully. Twenty-five patients who received the regimen as second line therapy had poor result with ORR 8.0% and DCR 76.0%. Hypertension was observed in 12 cases, with 8 cases of grade 1, 3 cases of grade 2, 1 case of grade 3. Various bleedings occurred in 24/77 cases (31.2%), all were of grade 1-2, including 17 cases of epistaxis, grade 1 hemorrhoid bleeding in one case, hematuria in 3 case (2 of grade 1, 1 of grade 2), GI bleeding in 2 cases, hemoptysis in 1 case (grade 2), and proteinuria in 4 cases (grade 1). Intestinal perforation occurred in 1 case (0.3%). In two patients who had incomplete intestinal obstruction history appeared exacerbated intestinal obstruction symptoms after the application of BEV plus CPT11 regimen.</p><p><b>CONCLUSIONS</b>BEV plus chemotherapy regimen as first-line treatment can improve the ORR and DCR of mCRC patients. When it was used as second- or later-line therapy, it may display satisfied DCR, although with a poor efficacy. The bevacizumab-related toxicity is mild and can be well tolerated.</p>

Novel micellar delivery system based on methoxy poly(ethylene glycol)-cholesterol / 中国药学杂志

OBJECTIVE: To synthesize methoxy poly(ethylene glycol)-cholesterol(mPEG-Chol), prepare mPEG-Chol micelles and investigate the in vitro cytotoxicity. METHODS: mPEG-Chol was achieved by conjugating cholesterol succinic ester(Chol-suc) with mPEG. mPEG-Chol micelles were constructed through different Methods including co-evaporation method, emulsion evaporation method and film dispersion method. The cytotoxicity of micelles was assessed systemically on different cell lines including MCF-7, MDA-MB-231, 4T1, SKOV-3 and AD293. RESULTS: mPEG-Chol was synthesized successfully with the yield of 70.3% and could form micelles via three different Methods. The size of mPEG-Chol micelles ranged from 20 to 150 nm. mPEG-Chol had no cell growth inhibition activity when set at the concentration of 20 μmol·L-1. The micelles showed different cytotoxicity compared with the mPEG-Chol molecular form. The IC50 values of micelles to SKOV-3 and MCF-7 were significantly lower than molecules. CONCLUSION: The synthesis process of mPEG-Chol is simple, cost-effective and easy to scale up massively. Micelles with low toxicity could be fabricated easily. Therefore, mPEG-Chol would be one of potential biomaterials to encapsulate various drugs with different solubility.

Impact of AJCC staging system (2010 edition) on the choice of postoperative adjuvant chemotherapy after radical resection of gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate whether AJCC staging system(2010 edition) for gastric cancer has influence on the adoption of adjuvant chemotherapy.</p><p><b>METHODS</b>This was a cohort study and the data were collected from patients who underwent radical surgery and received adjuvant chemotherapy from January 2004 to December 2009. There were 48 patients with stage II( disease and 95 patients with stage III( disease according to TNM staging(2010 edition). Doublets were defined as 5-fluorouracil or capecitabine plus cisplatin or oxaliplatin, while triplets had epirubicin added. Ninety-six patients received doublet chemotherapy and 47 received triplet. All the patients were followed-up in the outpatient clinic until death or the censor time of May 2011.</p><p><b>RESULTS</b>The median follow-up time was 48 months in this cohort of 143 patients. The two groups had similar disease-free survival(DFS)(median, 23 months vs. 30 months, P>0.05). The median overall survival was 48 months in both groups. Subgroup analysis by TNM staging(2010 edition) showed that the median DFS of patients with stage III( gastric cancer was 15 months in the doublet group, significantly shorter than that of patients in the triplet group (18 months, P<0.05). However, the difference in overall survival was not statistically significant between the two groups. Patients with stage II( disease had comparable DFS and OS between the two groups(all P>0.05).</p><p><b>CONCLUSIONS</b>Triplets regimens (epirubicin, platins and fluorouracil) show benefit on disease-free survival for the stage III( gastric cancer patients staged by TNM staging 2010 edition.</p>

Adjuvant chemotherapy for gastric cancer: more drugs do not mean better efficacy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare oncologic outcomes between doublet and triplet adjuvant chemotherapy for gastric cancer patients undergoing radical resection.</p><p><b>METHODS</b>Patients with gastric cancer receiving adjuvant chemotherapy after radical resection from January 2004 to December 2008 were included. Doublet was defined as 5-FU 750 mg/m² (days 1-5) or capecitabine 1000 mg/m² (days 1-14) plus cisplatin 60 mg/m² (day 1) or oxaliplatin 130 mg/m² (day 1), while triplets had epirubicin 50 mg/m² (day 1) added. Chemotherapy was initiated 4-6 weeks after surgery, repeated every three weeks for 6 cycles. Patients were followed-up in the outpatient clinic until death or the most recent follow up(April 30, 2010). Cox proportional- hazard model and Chi-square test were used to test statistical difference.</p><p><b>RESULTS</b>A total of 316 patients (210 received doublets, 106 received triplets) had a median follow-up time of 47 months. Seventy-seven patients died at the end of the follow-up. Two groups were comparable except for age (median age of 57 in doublets, 51 in triplets, P<0.01). The two groups had similar disease-free survival (16 months vs. 23 months, P=0.656) and 3-year overall survival(59.6% vs. 64.8%, P=0.293). There was no significant difference in severe adverse side effects between the two groups (21.9% vs. 30.2%, P=0.107).</p><p><b>CONCLUSION</b>Triplet adjuvant chemotherapy appears not to be associated with superior efficacy than doublet regimen for patients with gastric cancer after radical resection.</p>

Cost-effectiveness analysis of different chemotherapeutical regimens in metastatic colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare FOLFOX6 and FOLFIRI regimen in the treatment of metastatic colorectal cancer with cost-effective analysis.</p><p><b>METHODS</b>Cost-effective analysis was conducted based on the efficacy results of V308 clinical trial of FOLFOX6 and FOLFIRI regimen and the medical system price in Zhongshan hospital.</p><p><b>RESULTS</b>The minimal cost analysis showed FOLFIRI followed by FOLFOX6 had the cost of RMB 206365.78 Yuan for each patient during the whole treatment period, and RMB 170468.89 Yuan for the FOLFOX6 followed by FOLFIRI regimen. Incremental analysis showed FOLFIRI followed by FOLFOX6 regimen could prolong one month of overall survival with additional cost of RMB 39885.44 Yuan in each patient while compared with the regimen of FOLFOX6 followed by FOLFIRI.</p><p><b>CONCLUSIONS</b>Both FOLFOX and FOLFIRI regimens are able to prolong the survival time of patients with metastatic colorectal cancer, but cost of such treatments are still quite expensive for Chinese patients. FOLFOX6 regimen suggests better cost-effectiveness than FOLFIRI.</p>