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Renal cell carcinoma (RCC) is the third most common malignant tumor of the genitourinary system. During disease progression, RCC can undergo local and/or distant metastasis, which seriously affects the prognosis of the patient. With the advancements in targeted therapy and immunotherapy for advanced RCC, treatment for locally advanced RCC has changed. Studies have focused on applying targeted therapy or immunotherapy in the perioperative period. This article aims to review progress on treatment of locally advanced RCC to offer references for novel treatment strategies.
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Objective: To investigate the preliminary efficacy and safety of axitinib plus sintilimab in the treatment of intermediate- and high-risk advanced renal cell carcinoma. Methods: A retrospective study of patients with advanced renal cell carcinoma treated with axitinib and sintilimab was conducted in Peking University Cancer Hospital & Institute between April 2019 to December 2019. There were seven cases of clear-cell renal cell carcinoma and three cases of non-clear-cell renal cell carcinoma.All patients received 200 mg sintilimab intravenously every 3 weeks and 5 mg axitinib orally twice daily. Objective response rate (ORR), progression-free survival (PFS), and adverse effects were analyzed. Result: With the median age of 58.5 years (range 43.0-67.0), the patients were all classified as intermediate- and high-risk patients, according to the international metastatic renal cell carcinoma database consortium (IMDC) criteria. The overall ORR was 40.0% (4/10), and the disease control rate (DCR) was 90.0% (9/10). The ORR was 57.1% (4/7) in patients with clear-cell renal cell carcinoma. The main adverse effects included elevation of hepatic transaminases (number of patients, n=4; 40.0%), hypothyroidism (n=4; 40.0%), nausea (n=3; 30.0%), hypertension (n=2; 20.0%), and hand-foot skin reaction (n=2; 20.0%). Most adverse effects were of grade 1 or 2, but grade 3-4 adverse events occurred in three patients.Most adverse effects were ameliorated by effective symptomatic treatment. Conclusions: Axitinib plus sintilimab achieved promising ORR and DCR in patients with intermediate- and high-risk advanced renal cell carcinoma, with tolerable adverse effects.
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Objective To discuss and evaluate the clinical efficacy and safety of sunitinib for patients with advanced renal cell carcinoma and further to analyze the associated prognostic factors.Methods A retrospective analysis was performed in 78 cases with advanced renal cell carcinoma, receiving sunitinib therapy from April 2009 to December 2014.Patients consisted of 53 males and 25 females, with median age of 54 years old, ranged from 25-85 years old.Therapeutic regimen was described as following: 52 cases receiving sunitinib 50.0 mg/d 4 weeks on and 2 weeks off (4/2 regimen), 26 cases receiving 50.0 mg/d 2 weeks on and 1 weeks off (2/1 regimen).The dosage and regimen were adjusted according to the severity of side effects.Efficacy evaluation and drug-related toxicity were based on RECIST version 1.1 and CTCAE version 3.0.Progression-free survival (PFS) and overall survival (OS) were evaluated using the KaplanMeier method.Univariate and multivariate Cox proportional hazards model were used to assess the risk factors of PFS and OS.Results Nineteen cases switched from 4/2 to 2/1 regimen.Attenuated dosage was allowed in 49 cases to ameliorate drug-related toxicities.The most common drug-related toxicities were handfoot syndrome (HFS) in 63 cases (80.8％), diarrhea in 59 cases (75.6％), fatigue in 59 cases (75.6％) and thrombocytopenia in 6 cases (71.8％).The most common grade Ⅲ-Ⅳ toxicities were HFS in 9 cases (11.5％), thrombocytopenia in 6 cases (7.7％) and hypertension in 5 cases (6.4％).In RECIST evaluation, complete response (CR) was not recorded.8 cases (10.3％) achieved partial response (PR) , 59 cases (75.6％) kept stable disease (SD) and 11 cases (14.1％) suffered progressive disease (PD).The objective response rate (ORR) was 10.3％ and the disease control rate (DCR) was 85.9％.The median PFS was 11.0 months and median OS was 21.8 months.Multivariate Cox proportional hazards model showed two independent risk factors for PFS, including number of metastasis organs ≥ 2 and a high ECOG score.One independent risk factor for OS was number of metastasis organs ≥ 2.Conclusions Sunitinib shows encouraging efficacy and safety for patients with advanced renal cell carcinoma.Patients with multiple metastatic organs and poor performance status seems to be high risky of poor prognosis.
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With the increasingly deepening research on the molecular regulatory mechanisms during the development and progres-sion of advanced renal cell carcinoma, the targeted therapy directed on the key proteinase/protein in the molecular signaling pathways significantly improves the management outcomes. However, the occurring resistance during therapy with targeted agents leads to de-creasing effects. The mechanisms of action, resistance, and countermeasures of targeted therapy in advanced renal cell carcinoma are simply reviewed.
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Sunitinib as a multitarget tyrosine kinase inhibitor is one of the anti-tumor agents, approved by the United States Food and Drug Administration to use treat gastrointestinal stromal tumor and metastatic renal cell carcinoma. The agent is known to commonly induce adverse reactions such as fatigue, nausea, diarrhea, stomatitis, esophagitis, hypertension, skin toxicity, reduciton in cardiac output of left ventricle, and hypothyroidism. However, it has been reported to rarely induce adverse reactions such as nephrotic syndrome and irreversible reduction in renal functions, and cases of intestinal perforation or pneumatosis interstinalis as such reactions have been consistently reported. In this report, a 66-year old man showing abdominal pain had renal cell carcinoma and history of sunitinib at a dosage of 50 mg/day on a 4-weeks-on, 2-weeks-off schedule. Seven days after the third cycle he was referred to the hospital because of abdominal pain. Computed tomography showed pneumoperitoneum with linear pneumatosis intestinalis in his small bowel. The patient underwent surgical exploration that confirmed the pneumatosis intestinalis at 100 cm distal to Treitz's ligament. We report a rare case of intestinal perforation with pneumatosis intestinalis after administration of sunitinib to a patient with metastatic renal cell carcinoma.
Subject(s)
Aged , Humans , Male , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/drug therapy , Drug Administration Schedule , Indoles/adverse effects , Intestinal Perforation/diagnosis , Kidney Neoplasms/drug therapy , Lung/diagnostic imaging , Pneumatosis Cystoides Intestinalis/diagnosis , Positron-Emission Tomography , Pyrroles/adverse effects , Tomography, X-Ray ComputedABSTRACT
Objective To evaluate the efficacy and safety of sorafenib in the treatment of advanced renal cell carcinoma.Methods The clinical date of 33 patients with advanced renal cell carcinoma from September 2007 to April 2012 was reviewed retrospectively.26 were males and 7 were females,with an average age of 69 years.Pathological diagnosis showed 30 clear cell RCCs,2 papillary RCCs,and 1 unclassified RCC.These patients were treated by sorafenib 400 mg twice a day until intolerable toxicity or disease progression.The primary end points were objective response rate,clinical benefit rate,median survival time,median progression-free survival and the incidence of adverse reaction.Results All patients were evaluable for response and toxicity,with 8 patients (24％) of partial remission,19 cases (58％) of stable disease,and 6 cases (18％) of disease progression.The disease control rate was 82％,the median progression-free survival was 10.2 months,while the median survival time was 16.5 months.The common adverse reactions included hand-foot skin reaction (61％),diarrhea (46％),hypertension (21％).Most adverse reactions occurred around the second week after drug therapy,with the duration unequal.The majority of adverse reactions could be released by symptomatic treatment,which did not affect the medication.Conclusion Sorafenib has good short term efficacy for patients with advanced renal cell carcinoma,and most adverse reactions were tolerable.
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Surgical tumor resection, most appropriately together with the affected organ, is the sole form of curative therapy in low-staged renal cell carcinoma. But the fact that about 30% of patients show distant metastases or regional lymph node metastases at the time of diagnosis of renal cell carcinoma indicates the urgent need for the development of an effective treatment modalities. Herein we report the preliminary result of chemo-immuno-hormonal(triple) combination therapy which consists of a-interferon, vinblastine and medroxyprogesterone acetate in 17 patients with metastatic renal cell carcinoma from June 1990 to June 1994. The patients received the treatment with the combination of alpha interferon(a-IFN: 6 million units IM three times a week), vinblastine(VBL: 3 mgN2 IV monthly) and medroxyprogesterone acetate(MPA: 600 mg IM twice a month) at least 6 cycles. Although almost all the patients tolerated the treatment a few patients were stopped the treatment when the general condition of the patient became poor in progressive disease The 5 of 17 patients showed partial response and one patient with lung and liver metastasis was resolved completely. The response rate was 35.3% after treatment and the survival rates for 6 month and 1 year were 70.6% and 47.1%, respectively. So the chemo-immuno-hormonal combination therapymight be an alternative safe modality and be able to prolong the survival duration in patients with advanced renal cell carcinoma.
Subject(s)
Humans , Carcinoma, Renal Cell , Diagnosis , Drug Therapy , Liver , Lung , Lymph Nodes , Medroxyprogesterone , Medroxyprogesterone Acetate , Neoplasm Metastasis , Survival Rate , VinblastineABSTRACT
We evaluated the antitumor activity and toxicity of recombinant human interferon gamma (LBD -001) as a new modality for advanced renal cell carcinoma from March, 1988 to August, 1989 at the Department of Urology, St. Mary's Hospital, Catholic University Medical College. Eleven patients with advanced renal cell carcinoma were given recombinant gamma interferon at dose of 5.0-7.6 x 106U/day, subcutaneously three days per week. Among eleven patients, only one achieved partial response. Major adverse effects included fever, fatigue, myalgia and leukopenia, but no life threatening side effects were found. Although recombinant human interferon gamma have an antitumor activity against advanced renal cell carcinoma, further study is necessary to define the optimal treatment regimen.