Ai-Ping Zhou

Randomized, single-centered, phase II clinical trial of nimotuzumab plus cisplatin and S-1 as first-line therapy in patients with advanced gastric cancer.

e21021 Background: Nimotuzumab, a humanized IgG1 anti-EGFR monoclonal antibody, has demonstrated efficacy associated with an absence of severe skin toxicity in many phase I/II cancer trials. METHODS This is a single-center, randomized, parallel assignment and open-label study of nimotuzumab (N: 200 mg iv on day 1, 8 and 15, repeat every 3 weeks) + cisplatin (C: 30mg/m2/day, on day 1 and day 2, repeat every 3 weeks) + S-1 (S: 80mg/m2/day, twice daily on day 1-14, followed 7 days off), vs cisplatin (C: 30mg/m2/day, on day 1 and day 2, repeat every 3 weeks) + S-1 (S: 80mg/m2/day, twice daily on day 1-14, followed 7 days off) as first line in patients with advanced or metastatic gastric cancer. If tumor control was achieved, NCS and CS were continued until unacceptable toxicity or disease progression. The primary endpoint was ORR and the secondary endpoints included TTP, PFS, 1-year survival rates and safety. RESULTS 40 patients, 27 men and 13 women, median age 54 years (21-74 years) ECOG PS 0-2 were treated with NCS (n = 20) or CS (n = 20). Up to 2011-01-14, 36 patients (NCS 19 cases compared with CS 17) have undergone efficacy assessment. The objective response rate (ORR) was 63.2% (12/19) in NCS group compared with 64.7% (11/17) in CS group. Until the same day, 18 patients have achieved progression in both groups (NCS 10 vs. FCS 8), median TTP was 5.5 months in NCS group compared with 3 months in CS group, and average TTP was 5.3 months in NCS group compared with 3.1 months in CS group. The incidence of adverse events was similar between both groups. No adverse events of grade 3 skin rash or grade 3 infusion-related reactions were observed. CONCLUSIONS Initial results have demonstrated benefit in TTP improvement and showed a potential improvement of OS. This study supports that nimotuzumab combine with cisplatin and S-1 has better outcomes compare to cisplatin and S-1. The further study is ongoing.

Comparison of 627 patients with right- and left-sided colon cancer in China: Differences in clinicopathology, recurrence, and survival

Objective Recent studies have reported increased mortality for right-sided colon cancers; however, the results are conflicting for different stage tumors. We examined the differences in clinicopathology between right- and left-sided colon cancers and the relationships between colon cancer location (right- and left-side) and 5-year disease-free survival (DFS) and overall survival (OS). Methods We identified patients from 2005 to 2008 with stage II/III colon cancer who underwent surgery for curative intent. We explored the impact of the tumor location on the postoperative DFS and OS using univariate and multivariate analyses. Results Of 627 patients, 50.6% (317/627) had right-sided colon cancer. These patients were more likely to have weight loss, second primary tumor, elevated preoperative carbohydrate antigen 19-9 (CA19-9), increased incidence of non-adenocarcinoma, more poorly differentiated tumors, vascular invasion, defective mismatch repair, and a lighter smoking history (P < 0.05). Right-sided colon cancer had a higher recurrence incidence compared with left-sided cancer (30.6% vs. 23.2%, P = 0.037), particularly with multiple metastatic sites in the first recurrence (17.5% vs. 5.6%, P = 0.020). Kaplan–Meier survival curves demonstrated a significant difference in the 5-year DFS rate between right- and left-sided cancers across all stages (68.1% vs. 75.2%, P = 0.043). However, there was no significant difference in the 5-year OS rate between the two groups (73.8% vs. 79.0%, P = 0.103). Subgroup analysis demonstrated that patients with left-sided colon cancer had a significantly better 5-year DFS and OS rates compared with those with right-sided disease at stage III (64.3% vs. 46.8%, P = 0.002; 69.5% vs. 53.5%, P = 0.006, respectively); there were no significant differences in the 5-year DFS and OS rates at stage II (85.2% vs. 85.9%, P = 0.819; 89.8% vs. 88.5%, P = 0.803, respectively). Adjusted Cox regression analysis showed no significant differences in the 5-year OS and DFS rates for stage II [hazard ratio (HR) = 1.203, 95% confidence interval (CI): 0.605–2.391, P = 0.598; HR = 0.980, 95% CI: 0.542–1.774, P = 0.948, respectively] or all stages combined (HR = 0.867, 95% CI: 0.613–1.227, P = 0.421; HR = 0.832, 95% CI: 0.606–1.142, P = 0.255, respectively). However, stage III left-sided cancer had higher 5-year OS and DFS rates (HR = 0.626, 95% CI: 0.414–0.948, P = 0.027; HR = 0.630, 95% CI: 0.428–0.926, P = 0.019, respectively). Conclusion We found that right- and left-sided colon cancers had significantly different clinicopathological characteristics. Right-sided colon cancer had a higher incidence of recurrence than left-sided disease. Patients with stage III right-sided colon cancer had a worse prognosis compared with those with stage III left-sided colon cancer.

A study on the association between hyperlipidemia and hypothyroidism and the response to TKIs in metastatic renal cell carcinoma

Vascular endothelial growth facto receptor–tyrosine kinase inhibitors (VEGFR–TKIs) are widely used for metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the association between the response to VEGFR–TKIs and hyperlipidemia and hypothyroidism.

Evaluation of the optimal dosage of S-1 in adjuvant SOX chemotherapy for gastric cancer.

Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. The usual treatment of GC consists of surgery with additional adjuvant chemotherapy. In the present study, the feasibility and safety of adjuvant S-1 plus oxaliplatin (SOX) chemotherapy for patients with GC and the optimal dosage of S-1 were determined. Eligible patients were randomly assigned to either arm A (30 cases) receiving 70 mg/m2 S-1 (in two seperate half doses) daily or arm B (30 cases) receiving 80 mg/m2 S-1 (in two seperate half doses) daily. The S-1 was administered twice daily for 14 days followed by a 7-day rest period for the third week. A total of 130 mg/m2 oxaliplatin was administered on day 1 every 3 weeks for each arm. The cumulative rates of the relative total administration dose of S-1 at 100% in the 6th treatment course was 71.4% [95% confidence interval (CI), 56.5–90.3%] in arm A, which was significantly higher than 21.4% (95% CI, 10.5–43.6%) in arm B (P=0.001). The most common grade 3/4 toxicities were neutropenia (19.6%), thrombocytopenia (19.6%) and vomiting (16.1%). Grade 3/4 thrombocytopenia was observed in 7.1% of patients in arm A and in 32.1% of patients in arm B (P=0.019). With regard to the adverse events induced by S-1 administration, the incidence of diarrhea (3.6 vs. 42.9%; P<0.001) was significantly higher in arm B than in arm A, as anticipated. Collectively, adjuvant SOX therapy for GC is feasible and safe, and when combined with 130 mg/m2 oxaliplatin, 70 mg/m2/day S-1 appears to the optimal dose.

Chinese guidelines on the management of renal cell carcinoma (2015 edition)

The guideline was established by the kidney cancer panel under the Chinese Society of Clinical Oncology (CSCO) in accordance with the basic principles of evidence-based medicine ( Table 1 ) and the clinical practices on renal cancer in China, based on the real conditions of China, and by referring to the USA NCCN Clinical Practice Guidelines in Oncology-Kidney Cancer (1) and the European Association of Urology (EAU) Guidelines on Renal Cell Carcinoma (2). The renal cancer referred in these guidelines is the renal cell carcinoma (RCC) and does not include various tumors originated from renal interstitium and renal pelvis/urothelial system.

Impact of Cytoreductive Nephrectomy on Survival in Patients with Metastatic Renal Cell Carcinoma Treated by Targeted Therapy.

Background: The metastatic renal cell carcinoma (mRCC) patients treated with upfront cytoreductive nephrectomy combined with &agr;-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. Methods: 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 &agr; = 0.05. Results: 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. Conclusions: 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.

Body mass index and age are additional prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

PURPOSE Tyrosine kinase inhibitors (TKIs) are the preferred treatment drugs for metastatic renal cell carcinoma (mRCC). The aim of this study was to analyze prognostic factors for overall survival (OS) in patients with mRCC treated with TKIs. MATERIALS AND METHODS Clinical data on 155 patients enrolled in 5 clinical trials conducted at our hospital from 2006 to 2014 were reviewed retrospectively. All patients received first-line TKI therapy (sunitinib, sorafenib, pazopanib, or famitinib). Survival rates were determined by the Kaplan-Meier method. RESULTS Median OS (mOS) was 36.2 months. A total of 4 of the 5 adverse prognostic factors identified by the Memorial Sloan-Kettering Cancer Center (MSKCC) were found to be independent predictors of shorter survival, anemia, hypercalcemia, lactate dehydrogenase>1.5×upper limit of normal, and diagnosis to treatment time<1 year. In addition, we found that age≤45 years (P = 0.002), low or high body mass index ([BMI]<19 or>30kg/m(2)) (P = 0.003), and presence of≥3 metastatic sites (P = 0.000) were also independent adverse prognostic factors. According to the MSKCC model, the mOS time in the favorable-risk, intermediate-risk, and poor-risk groups were 46.6, 30.4 and 16.7 months, respectively (P = 0.005). When we integrated age and BMI into the MSKCC model to set up a 7-factor prognostic model, we found the mOS time for these 3 groups was 71.1, 41.6 and 15.3 months, respectively (P = 0.000). CONCLUSION Age and BMI are additional independent prognostic factors for patients with mRCC receiving vascular endothelial growth factor receptor-targeted TKI treatment, and the MSKCC prognostic model is also applicable to them. A 7-factor prognostic model might help to identify patients with the best prognosis. Further studies are needed to confirm these findings.

Clinicopathological characteristics and treatment outcomes of Chinese patients with genitourinary embryonal rhabdomyosarcoma

BackgroundGenitourinary embryonal rhabdomyosarcoma is rarely reported in China. This retrospective analysis aimed to characterize the clinicopathologic features and treatment outcomes of genitourinary embryonal rhabdomyosarcoma in a sample of Chinese patients.MethodsBasic demographic and clinical data of 29 patients, who were diagnosed with genitourinary embryonal rhabdomyosarcoma between January 2000 and December 2011, were retrieved and analyzed.ResultsIn these patients, 25 were males and 4 were females with a median age of 12 years. Paratesticule was the most common lesion site, followed by the prostate, bladder, and vagina. The median tumor size was 5.80 cm. Six patients had clinically positive regional nodes. At the initial diagnosis, patients had a metastatic disease. According to the TNM staging classification for the IRS-IV, phase I lesions were detected in ten cases, phase II lesions in six cases, phase III lesions in four cases, and phase IV lesions in nine cases. The median survival of all patients was 63 (range from 6 to 118) months. The 1-, 3-, and 5-year survival rates for these patients were 93%, 83%, and 52%, respectively. Multivariate analyses demonstrated that staging and anemia were significant predictors of prognosis.ConclusionsOur findings suggest that metastasis predicts a poor prognosis. Chemotherapy played an important role in comprehensive treatment. Palliative and neo-adjuvant chemotherapy could increase median survival time.

Prognostic factors associated with locally advanced gastric cancer patients treated with neoadjuvant chemotherapy followed by surgical resection

In this retrospective study, we analyzed prognostic factors associated with survival outcomes in 73 locally advanced gastric cancer patients treated with neoadjuvant chemotherapy (NAC) followed by surgical resection. Median disease-free survival (DFS) for 64 patients that received R0 resection was 685 days, whereas median overall survival (OS) for 73 patients was 930 days. Multivariate analysis demonstrated that post-treatment nodal stages (P = 0.002), nervous invasion (P = 0.0492) and serum CA199 levels (P = 0.0398) were independent prognostic factors for DFS. Nodal stages (P = 0.0007), presence of nervous invasion (P = 0.0259) and non-radical resection (P = 0.0165) were independent prognostic factors for OS. These results indicate that post-treatment nodal stages, neural invasion and serum CA199 levels are all associated with poor DFS. Moreover, post-treatment nodal stage, resection type and neural invasion status are independent prognostic factors for OS.

CYP2A6 Polymorphisms Associate with Outcomes of S-1 Plus Oxaliplatin Chemotherapy in Chinese Gastric Cancer Patients

Gastric carcinoma is a heterogeneous malignant disease involving genetic factors. To identify predictive markers for gastric cancer treatment in Chinese patients, we evaluated the association between polymorphisms of the gene encoding cytochrome P450 2A6 (CYP2A6) and outcomes of S-1 plus oxaliplatin (SOX) chemotherapy treatment. Clinical data on 60 consecutive gastric cancer patients receiving SOX regimen were collected prospectively. We sequenced all exons of CYP2A6 and a total of 22 different polymorphisms were detected in the present study. Comprehensive analyses of these genetic polymorphisms were performed to determine their association with both safety and efficacy of SOX regimen. Our results showed that polymorphisms of CYP2A6 were associated with the safety and efficacy of SOX treatment. Among them, missense mutations CYP2A6 rs60823196 and rs138978736 could be possible risk factors (P < 0.05) for severe diarrhea induced by SOX, whereas CYP2A6 rs138978736 could be a conceivable predictor for overall survival of patients treated with SOX adjuvant chemotherapy. Further large-scale randomized prospective studies are warranted to confirm these findings.