Systemic chemotherapy for patients with advanced biliary tract cancer: a single-center retrospective study / 中华肝胆外科杂志

Objective:To study the efficacy of different systemic chemotherapy regimens as first-line and second-line therapy and to determine the prognostic factors for patients with advanced biliary tract cancer.Methods:The clinical data of patients with advanced biliary tract cancer who underwent systemic chemotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2018 were studied. The efficacy of chemotherapy on objective response rate (ORR) and disease control rate (DCR) were evaluated. Potential prognostic factors for survival were studied using the Cox proportional hazards models.Results:Of 151 patients enrolled into this study, there were 75 males and 76 females, with ages ranging from 31 to 77 years (median 58 years). Two treatment protocols were used: (1) 104 patients received a gemcitabine-based regimen (combined with platinums or fluorouracils) or a combination of platinums and fluorouracils, while (2) 47 patients received a combination of albumin-bound paclitaxel and S-1. The corresponding ORR for each group were 15.4%(16/104) and 27.6%(13/47), respectively, and the DCR were 65.4%(68/104) and 72.3%(34/47), respectively. Of 58 evaluable patients who received chemotherapy as a second-line therapy, 31 patients received the regimen containing gemcitabine, platinums or fluorouracils with an ORR of 3.2% (1/31) and a DCR of 35.5%(11/31); a total of 18 patients received the taxanes-based regimen with an ORR of 11.1%(2/18) and a DCR of 38.9%(7/18); 9 patients received the irinotecan-based regimen with an ORR of 22.2%(2/9) and a DCR of 44.4%(4/9). Univariate analysis showed positive liver metastasis and elevated carbohydrate antigen (CA)19-9 level to be significantly correlated with worse survival outcomes ( HR=1.540, 95% CI: 1.019-2.328, P=0.040 and HR=1.892, 95% CI: 1.123-3.188, P=0.017). Conclusion:For patients with advanced biliary tract cancer, in addition to the conventional regimens containing gemcitabine, platinums and fluorouracils, the combination of albumin-bound paclitaxel and S-1 was shown to be an effective chemotherapeutic regimen for these patients. Second-line chemotherapy was insufficient and ineffective, and an irinotecan-based regimen deserves to be further investigated. Liver metastasis and elevated CA19-9 level were worse prognosis after chemotherapy for patients with advanced biliary tract cancer.

Efficacy observation of irinotecan combined with capecitabine or tegafur-gimeracil-oteracil potassium in the second-line treatment of advanced colorectal cancer / 肿瘤研究与临床

Objective To observe the clinical efficacy of irinotecan combined with capecitabine or tegafur-gimeracil-oteracil potassium in the second-line treatment of advanced colorectal cancer. Methods The clinical data of 19 patients with advanced colorectal cancer who were admitted to the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from October 2014 to December 2017 were retrospectively analyzed, and these patients failed the first-line chemotherapy regimen. All patients were treated with irinotecan plus capecitabine or tegafur-gimeracil-oteracil potassium. The patient's short-term efficacy, adverse reactions, progression-free survival, and overall survival were analyzed. Results After treatment, the efficacy in 18 of the 19 patients with advanced colorectal cancer was evaluable, including partial remission in 3 patients, stable disease in 13 patients, and disease progression in 2 patients. The objective remission rate was 16.7％ (3/18), the disease control rate was 88.9％ (16/18), the median progression-free survival time was 7.6 months, and the median overall survival time was 23.3 months. All of the patients were well tolerated , and the grade 4 adverse reaction was presented as grade 4 neutropenia (1 case), grade 3 leukopenia (2 cases) and thrombocytopenia (1 case), grade 2 diarrhea (1 case), and grade 1 diarrhea (3 cases), and grade 1-2 liver injury (3 cases) and nephrotoxicity (2 cases). Conclusion Irinotecan combined with capecitabine or tegafur-gimeracil-oteracil potassium in the treatment of advanced colorectal cancer is effective and safe, which is worthy of clinical promotion.

FOLFOX/XELOX plus cetuximab administered weekly versus biweekly as a first-line treatment for patients with KRAS/RAS wild-type metastatic colorectal cancer: a retro-spective study / 中国肿瘤临床

To compare the efficacy and safety of cetuximab biweekly regimen with those of standard weekly regimen as a first-line therapy of KRAS/RAS wild-type metastatic colorectal cancer. Methods: Patients who received weekly or biweekly administra-tion of cetuximab plus FOLFOX/XELOX as a first-line therapy from July 2010 to December 2017 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively screened for eligibility. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and frequencies of adverse events (AEs) between the two groups were compared. Results: Of 152 eligible patients, 55 were in the biweekly group and 43 were in the weekly group. The biweekly group had significantly higher ORR than the weekly group (76.3% vs. 54.8%, P=0.025). Median PFS in the biweekly and weekly groups were 10.3 and 8.8 months, respectively (P=0.288), and the median OS were 33.5 and 27.4 months, respectively (P=0.563). The two groups showed no significant difference in PFS and OS. For overall AEs, the biweekly group presented significantly more stomatitis (32.7% vs. 14.0% , P=0.032) and tended to show substantially more acne-like rash (80.0% vs. 62.8%, P=0.058) and leukopenia and/or neutropenia (72.7% vs. 55.8%, P=0.081). The frequency of 3/4 grade acne-like rash in the biweekly and weekly groups were 18.2% and 7.0%, respectively (P=0.105). The frequency of all grade 3/4 AEs between the two groups showed no significant difference (P>0.05). Conclusions: Biweekly regimen of cetuximab plus FOLFOX/XE-LOX had similar efficacy and higher ORR compared with those of standard weekly regimen. Cetuximab administered biweekly may be an optional choice in clinical practice, with close attention paid to increased frequency of certain AEs.

Detection and significance of epidermal growth factor receptor mutation in esophageal, esophagogastric junction and gastric cancers / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have been reported to be effective in the treatment of esophageal and esophagogastric junction cancers. The aim of this study was to detect the frequency of EGFR mutation and expression in Chinese patients with esophageal, esophagogastric junction and gastric cancers, and to clarify the value of EGFR mutation and expression in predicting the efficacy of TKI in the treatment of these tumors.</p><p><b>METHODS</b>In this study, 180 tumor samples with histologically confirmed esophageal cancer (39 cases), cancer of the esophagogastric junction (92 cases) and gastric cancer (49 cases) were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by real-time PCR-optimized oligonucleotide probe method. EGFR protein expression was evaluated by immunohistochemistry (IHC) in 89 tumor samples.</p><p><b>RESULTS</b>The mutation analysis for EGFR (exons 18-21) showed no mutations in any of the hotspots of the gene in the 180 tumor samples analyzed. EGFR expression was negative in 12 tumor samples, 1+ in 31 tumor samples, 2+ in 24 tumor samples, and 3+ in 22 tumor samples. EGFR expression was 2+ or 3+ in 12 (92.3%) of the 13 esophageal squamous cell carcinomas, 29 (47.5%) of the 61 esophagogastric junction cancers, and 5 (33.3%) of the 15 gastric adenocarcinomas.</p><p><b>CONCLUSIONS</b>Our results indicate that EGFR mutation in exons 18-21 is absent in the examined samples of esophageal, esophagogastric junction and gastric cancers. More studies are warranted to explore the predictive biological markers for the therapeutic response to EGFR TKI.</p>

Clinical analysis of 32 metastatic gastric cancer patients who un-derwent surgery after chemotherapy / 中国肿瘤临床

Objective:To examine metastatic gastric cancer patients who underwent surgery after chemotherapy and to determine the factors affecting survival. Methods:Clinical data on metastatic gastric cancer patients who underwent surgery after chemotherapy were retrospectively analyzed. The overall survival data were evaluated through the Kaplan-Meier method, Log-rank test, and Cox haz-ards regression. Results:The median age was 46 (22~74), and the median overall survival rate (OS) was 19 months (4~59 months). Response to chemotherapy (23.0 m for PR and 14.5 m for SD, P=0.045) and resection of the primary tumor (23.0 and 5.5 m, respective-ly, P=0.017) affected OS. No single factor was related to OS according to Cox regression. Conclusion:Surgical removal of the primary tumor is recommended for metastatic gastric cancer patients with positive response to chemotherapy and with a primary tumor that can be resected.

Clinical study of sorafenib for patients with advanced renal cell carcinoma / 中华泌尿外科杂志

Objective To evaluate the safety and efficacy of sorafenib for patients with advanced stage renal cell carcinoma.Methods The clinical data of 85 patients with advanced renal cell carcinoma were reviewed.These patients were treated by sorafenib 400 mg Bid,dose escalation of sorafenib(400 mg Bid 1-4 weeks;600 mg Bid 5-8 weeks;800 mg Bid since then) or sorafenib 400 mg Bid+NF-α,respectively,until intolerance or disease progression occurred.The primary end points were objective response,disease control rate and adverse effects rate.Results The data of 80 patients can be evaluated.The median follow-up duration was 72 weeks (4-108 weeks).One patient (1.2%) reached complete remission(CR),17 cases(21.2%) reached partial remission(PR),50 cases (62.5%) maintained stable disease (SD),and 12 cases (15%) progressed.The objective response (CR+PR) was 22.5%,disease control rate (CR+PR-SD)was 85.0%.By May 2009,only 18 patients died,progression free survival and overall survival were not available.The common side effects included hand-foot skin reaction (55.0%),mucosa hemorrhage (52.5%),diarrhea(40.0%),lassitude (35.0%),anorexia(22.5%),mucosa ulcer(20.0%),hypertension(15.0%) and baldness(15.0%)etc.Most of these side effects could be released by symptomatic treatment.Conclusion Sorafenib has good short term effect for patients with advanced renal cell carcinoma and is well tolerated.

Clinical study of sorafenib in the treatment of Chinese patients with metastatic renal cell carcinoma / 中华泌尿外科杂志

Objective To evaluate the efficacy and safety of sorafenib in the treatment of Chi-nese patients with metastatic renal cell carcinoma. Methods This muhicenter phase Ⅱ clinical trial was performed from May 2006 to December 2006. Sixty-two patients with metastatic renal cell carci-noma not suitable for curative treatment were enrolled. All patients received oral sorafenib as single a-gent at the dose of 400 mg twice a day until disease progression or intolerable toxicities occurred. Re-salts Partial responses were recorded as best response in 11 patients, while complete remission was found in 1 patient and stable diseases were found in another 35 patients. According to the intents-to-treatment population, the overall response rate was 19.4% (12/62), and the disease control rate was 77.4%(48/62). The median progression free survival time was 9.6 months with 1-year progression-free survival rate of 41.9%. However, the median survival time had not reached due to the short fol-low-up. The most frequent adverse events included alopecia (66.1%), diarrhea (62.9%), hand-foot syndrome (58.1%), anorexia (40.3%), rash(37.1%), fatigue (37.1%), hypertension (35.5%), hoarseness(32.3%), joint pain (25.8%), hypophosphatemia (21.0%), fever (19.4%), nausea (19.4%), abnormal transeaminase( 11.3% ), elevated total bilirubicin( 16.1% ), leucopenia( 12.9% ), bleeding under nail(16.1%), and gum bleeding(11.3%). Grade 3 adverse events included hand-foot syndrome (16.1%), hypertension (12.9%), diarrhea(6.5%), hypophosphatemia (4.8%), joint pain (3.2%), and leucopenia(3.2%). Conclusions Sorafenib has prominent anti-tumor activity in Chi-nese metastatic renal cell cancer patients with most adverse events being grade 1 or 2. More attention should be paid to hypertension and cardio-cerebral vascular events during the application of sorafenib.