Clinical Efficacy And Prognostic Factors For Overall Survival In Chinese Patients With Advanced Renal Cell Carcinoma Treated With VEGF-targeted Agents In China

Ⅰ.Validation of the MSKCC model in patients with advanced RCC treated with VEGF-targeted agents in ChinaObjective To investigate the clinical efficacy of vascular endothelial growth factor (VEGF)-targeted agents in treating advanced renal cell carcinoma (RCC) in china and validate the MSKCC model.Methods Three hundred and forty-five patients with advanced RCC and an average age of57yrs (17-90yrs) were treated with VEGF-targeted agents. Pathological diagnosis showed206cases of clear cell RCC,20cases of papillary RCC,4cases of chromophobe RCC,5cases of renal collecting duct carcinoma,3cases of medullary carcinoma and7cases of unclassified RCC. The main metastatic lesions were located at lung, bone and lymph nodes. In them, Two hundred and five cases were given the treatment of sorafenib400mg bid without off treatment, while one hundred and forty cases received sunitinib treatment in repeated six week cycles consisting of four weeks of sunitinib50mg daily followed by two weeks off treatment. Overall survival was estimated by the Kaplan-Meier method. Log-rank test and Harrell concordance index analysis were used to validate the MSKCC Score Model.Results The mean follow-up period was23months (from1-68months) in the whole group. The overall survival was33months, and survival rates at1-,2-,3-year were77.6%(95%CI:0.733-0.823),59.3%(95%CI:0.538-0.653),46.6%(95%CI:0.397-0.546), respectively. According to the Memorial Sloan-Kettering Cancer Center (MSKCC), patients were segregated into three risk categories:the favorable-risk group (no prognostic factors; n=169;49%), in which median OS (mOS) was46months and2y OS was75.8%; the imtermediate-risk group (one or two prognostic factors; n=150;43%), in which mOS was24months and2y OS was47.7%; and the poor-risk group (three to five prognostic factors; n=26;8%), in which mOS was7.5months and2y OS was10.1%(log-rank p<0.01). The C-index was0.687.Conclusion VEGF-targeted agents were effective in China patients with advanced RCC. The MSKCC model was validated and can be incorporated into judging individualizing tumor prognosis and communication in treatment options with patients that use VEGF-targeted agents. Ⅱ. Conditional survival in patients treated with vascular endothelial growth factor-targeted therapy for advanced renal cell carcinomaObjective Conditional survival (CS) offers more relevant pognostic information for patients once they have sur-vived for some time. The objective of this study was to determine the CS for advanced renal cell carcinoma (RCC) patients treated with vascular endothelial growth factor-targeted therapy.Methods A total of345patients treated between2006and2011fulfilled the inclusion criteria and were reviewed for analyses. The1-year conditional and actual survival rates were calculated for survivors from treatment to month24. Subgroup-specific CS rates were generated after adjustment of the covariate influence. The Cox proportional hazard models were used to assess the prognostic factors at baseline and1-year landmark.Results The probabilities of surviving an additional year given survival to6,12,18, and24months were72.2,76.3,78.2, and78.6%, respectively. Remarkable increase in CS was observed in patients initially classified as intermediate or poor risk according to Heng risk groups. For patients survived24months after treatment, the adjusted CS for the following year was over80%regardless of initial risk attribution. Compared to baseline analysis, Heng risk groups were less predictive of survivorship after surviving1year. The addition of disease control status to multifactorial model significantly improved survival estimation for1-year survivors (p<0.01).Conclusions CS provides useful information regarding life expectancy for survivors of advanced RCC treated with targeted therapy. Furthermore, disease control status within a specific period of time is critical to the prediction of subsequent survival. Ⅲ. Adverse reaction effects in patients with RCC treated with sunitinibObjective To study the early kinetics of adverse events after sunitinib, and explored their association with clinical outcome in patients with advanced RCC treated with sunitinib.Methods One hundred and thirty-six patients with advanced renal cell carcinoma were treated with sunitinib in our hospital from2008to2011. Of them,91were male and45were female with average age of55.5yrs. These patients received sunitinib treatment in repeated six week cycles consisting of four weeks of sunitinib50mg per day followed by two weeks off treatment (schedule4/2). The hematologic toxicities, collected at baseline and14,28,42(after a2-week rest period) days, were graded according to the national cancer institute common terminology criteria for adverse events version3.0. The paired Wilcoxon test was used to evaluate the kinetics of hematologic adverse effects at days14,28, and42after initiation of sunitinb treatment. Correlation between toxicities and overall survival (OS) was evaluated in a Cox model using log-transformed levels after adjusting for MSKCC model. The log-rank test and Cox proportional hazard models were used to assess the value of drug toxicity as the prognostic factors.Results The hematologic toxicities of these patients included leukopenia (91cases;66.9%), neutropenia (95cases;69.8%), lymphopenia (58cases;46.2%), thrombopenia (89cases;65.5%) and hypohemoglobinemia (48cases;35.3%). Of them,31cases (22.8%) got the high grade (including grade3and grade4) toxicity of thrombopenia. Sunitinib treatment resulted in depression in hematopoiete cell populations including leukocytes, neutrophils, and platelets at days14,28and42compared with baseline level (all p<0.05). The median of hemoglobin level transient increased at days14and28(P<0.001; P<0.002) and returned to the level of baseline at days42(P=0.754). The extent of the early increase in hemoglobin and lymphocytes and the development of nonhematologic toxicities (i.e., hypertension toxicities), were significantly associated with overall survival.Conclusions The incidences of hematologic adverse effects of sunitinib slightly vary with what have been observed in studies.This explorary study suggests that early hematopoietic toxicities may potentially predict outcome in advanced RCC after sunitinib treatment.