舒尼替尼在晚期肾细胞癌二线序贯治疗中的临床应用研究

目的:探讨舒尼替尼在晚期肾细胞癌(renal cell carcinoma,RCC)患者二线序贯治疗中的临床效果与安全性。方法:对11例曾接受其他靶向药物治疗的晚期RCC患者在我院行二线舒尼替尼治疗,观察其客观缓解率(ORR)、疾病控制率(DCR)、中位无进展生存期(PFS)及总生存期(OS)等疗效指标及不良反应发生情况。结果:11例患者中2例因不良反应进行药物减量,1例终止治疗。平均接受舒尼替尼治疗时间10.2个月,9例死亡,2例仍存活。DCR 90.9%,中位PFS为7.4个月,中位OS为22.6个月。主要不良反应包括血小板减少症、白细胞减少症、手足皮肤反应、甲状腺功能低下、高血压等。结论:舒尼替尼序贯治疗对于接受过其他靶向药物治疗后进展的晚期RCC患者仍具有良好的疗效和安全性。     

舒尼替尼在晚期肾细胞癌治疗中的运用

目的：探讨苹果酸舒尼替尼对晚期肾细胞癌治疗的安全性和有效性。方法：晚期肾细胞癌患者22例,男18例,女4例,平均年龄56岁,均为转移性或难以手术的肾细胞癌患者。采用舒尼替尼治疗,其中18例为一线治疗,4例为二线治疗。均为单一服药,口服50mg／d,每4周停药2周者16例;口服37．5mg／d,连续服药者6例。持续用药至肿瘤进展或出现不可耐受的并发症。以6周为1个治疗周期,至少每2个治疗周期进行疗效评价。结果：1例患者服药不足2周期内死亡,可评价病例21例。部分缓解6例（28．6％）,疾病稳定13例（61．9％）,疾病进展2例（9．5％）,无完全缓解病例。常见的不良反应包括手足皮肤反应、皮疹、疲劳乏力、骨髓抑制、味觉变化等。结论：舒尼替尼治疗晚期肾癌患者效果确切,不良反应多数可控制,但对于KPS评分较低,一般情况差,肿瘤负荷大的患者,运用时需慎重。     

Efficacy of traditional and alternative sunitinib treatment schedules in Japanese patients with metastatic renal cell carcinoma

We report the adverse events and efficacy of traditional (4 weeks on 2 weeks off) and alternative sunitinib treatment schedules for Japanese patients with metastatic renal cell carcinoma. We retrospectively investigated 54 patients who received sunitinib for metastatic renal cell carcinoma between May 2006 and June 2012: 32 received a traditional treatment schedule and 22 received an alternative schedule. According to the Memorial Sloan‐Kettering Cancer Center risk classification, five patients had favorable prognoses, 42 had intermediate prognoses and seven had poor prognoses. The mean observation periods were 16.3 and 20 months for the traditional and alternative schedule groups, respectively. Adverse events were significantly less common in the alternative schedule group, including most high‐grade events. In the traditional and alternative schedule groups, median times to failure were 4.1 and 11.6 months (P = 0.040), median progression‐free survival times were 4.1 and 11.3 months (P = 0.031), and median overall survival times were 12.0 and 32.1 months (P = 0.018), respectively. Each of these measures was better in the group of patients who received an alternative treatment schedule, suggesting that individualized changes to the sunitinib administration schedule can be effective.     

Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with severe renal impairment or on haemodialysis

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Sunitinib is approved for the first‐ and second‐line treatment of advanced renal cell carcinoma (RCC). Chronic kidney disease is commonly seen in patients with RCC, but knowledge regarding the effect of sunitinib in patients with severe renal impairment or on haemodialysis is limited. In this study we define the toxicity profile and clinical outcomes of a patient cohort with RCC with severe renal impairment, or on haemodialysis who were treated with sunitinib. This retrospective study suggests that these patients can be safely treated with sunitinib at the standard dose, and the observed efficacy of therapy is similar to that reported in patients with normal renal function.

OBJECTIVE

To further investigate the effect of sunitinib, which is currently a standard of care for the treatment of metastatic renal cell carcinoma (mRCC), in patients with severe renal impairment or those undergoing dialysis.

PATIENTS AND METHODS

Clinical databases were used to identify all patients with mRCC treated with sunitinib in seven institutions internationally. Databases were searched to identify only those patients with an estimated glomerular filtration rate of <30 mL/min/1.73 m² or those who had end‐stage renal disease requiring dialysis. Baseline characteristics, adverse event data, response and progression‐free survival were recorded.

RESULTS

Nineteen patients met the inclusion criteria, 10 of whom were undergoing haemodialysis. Of the nine non‐dialysis‐dependent patients at drug initiation, the median estimated glomerular filtration rate was 27 mL/min/1.73 m² (range 23–29). Baseline characteristics included a median age of 61 years (range 44–77); 17 patients had a Karnofsky performance status of >80; eight patients had more than two metastatic sites and 17 had undergone prior nephrectomy. The estimated median progression‐free survival of this cohort was 43 weeks (range 7 to 158+) and progression has not yet been reached in six patients. Partial response or stable disease was observed as best response in 15 patients. The most common treatment‐related adverse events included fatigue, diarrhoea, hand–foot skin reaction (HFSR), nausea and vomiting and rash. Grade three treatment‐related adverse events including fatigue (seven patients), HFSR (two patients), diarrhoea (one patient), rash (one patient) and stomatitis (one patient) occurred in a total of 12 patients. Only one patient experienced a grade four adverse event (HFSR). Only diarrhoea (P = 0.0002), HFSR (P < 0.0001) and neutropenia (P = 0.001) were more common in patients undergoing haemodialysis compared with non‐dialysis‐dependent patients. Four of the non‐dialysis dependent patients started at a dose of 50 mg compared with three of the patients undergoing haemodialysis. However five and two of the patients undergoing haemodialysis started at doses of 37.5 mg and 25 mg daily, respectively, compared with four and one of the non‐dialysis‐dependent patients. All patients took sunitinib for 4 out of every 6 weeks. Dose reductions during treatment were performed in eight patients but only one patient required discontinuation of treatment.

CONCLUSION

These data suggest that patients with severe renal impairment or end‐stage renal disease on haemodialysis can be safely treated with sunitinib at doses of 25–50 mg daily for 4 weeks followed by a 2‐week break. The observed efficacy of therapy is similar to that reported in patients with normal renal function. These preliminary results warrant confirmation in a larger cohort of patients.     

C‐reactive protein as a prognostic marker for advanced renal cell carcinoma treated with sunitinib

Objectives: To investigate the prognostic role of C‐reactive protein in patients with advanced renal cell carcinoma treated with sunitinib. Methods: A total of 41 consecutive patients with advanced clear‐cell renal cell carcinoma treated with sunitinib between December 2008 and August 2011 were included in this study. Logistic regression analysis estimated the relative importance of non‐tumor variables, including C‐reactive protein, and selected adverse events as predictive factors for sunitinib responses. Results: Overall, 11 patients (26.8%) showed a partial response and 10 patients (24.4%) had stable disease. On univariate analysis, Memorial Sloan‐Kettering Cancer Center non‐poor risk, normal C‐reactive protein, hand–foot skin reaction, altered taste, fatigue and leukopenia were significantly correlated with objective responses (P = 0.020, 0.001, 0.006, 0.006, 0.023 and 0.037, respectively). On multivariate analysis, normal C‐reactive protein was independently associated with objective response (P = 0.016). Patients with a normal level of C‐reactive protein (≤0.30 mg/dL) had a significantly higher partial response plus stable disease rate (84.6% vs 35.7%, P = 0.002) and significantly longer progression‐free survival (median 19.0 vs 6.0 months, P = 0.036) than patients with an elevated level of C‐reactive protein. Conclusions: C‐reactive protein is an independent prognostic indicator for patients with advanced renal cell carcinoma treated with sunitinib.     

Adrenal metastasis from renal cell carcinoma: Significance of adrenalectomy

BACKGROUND: The present study examined adrenal metastasis resulting from renal cell carcinoma (RCC), with the aim of assessing the need for routine ipsilateral adrenalectomy during radical nephrectomy. METHODS: Ipsilateral and contralateral adrenal metastases were investigated in 256 patients with RCC who had undergone radical nephrectomy from 1977 to 1996 at the Tohoku University School of Medicine. RESULTS: Twelve of the 256 patients (4.7%) had adrenal metastasis. Ten of these 12 patients had progressed to disseminated disease with very poor prognosis. Two patients who had solitary adrenal metastases remained disease-free for 21 and 7 years. Four patients showed metastases to the contralateral adrenal gland. Adrenal metastases in seven of 12 patients were identified by pre- or postoperative computed tomography (CT), and in another five macroscopically during surgery. CONCLUSIONS: Adrenalectomy was regarded as a possible curative treatment for patients with solitary adrenal metastasis. However, the incidence of this kind of metastasis was minimal and contralateral adrenal metastases may occur in RCC cases. We therefore believe that adrenalectomy should only be performed if radiographic evidence reveals metastases in the adrenal gland or if gross disease is present at the time of nephrectomy.     

Clinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma treated with sunitinib and sorafenib after progression on cytokines

ObjectivesThe aim of this retrospective study was to analyze prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors (TKIs) sunitinib or sorafenib after progression on cytokine therapy.Materials and methodsA national database of patients treated with targeted agents was used as the data source. A total of 319 patients treated with sunitinib (n = 181) or sorafenib (n = 138) after progression on cytokine therapy were analyzed.ResultsPrognostic factors significantly associated with poor overall survival in a multivariable Cox model included the time from diagnosis to the start of treatment with TKIs<1 year, increased neutrophil counts, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. The parameters showing statistically significant association with progression-free survival included time from diagnosis to the beginning of treatment with TKI<1 year, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. We have also validated the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model in our cohort of patients.ConclusionWe demonstrate that the International Database Consortium prognostic model performs well for European patients treated with TKIs, including sunitinib or sorafenib, after progression on cytokines and suggest that a reduction from original 6 down to 4 parameters is possible.     

Pathological evidence of necrosis in recurrent renal mass following treatment with sunitinib

Sunitinib is a highly potent, selective vascular endothelial growth factor-receptor types 1 to 3, platelet-derived growth factor (PDGF)-R-alpha, and PDGF-R-ss. Preclinical data suggest that sunitinib (SU11248) has antitumor activity that may result from both inhibition of angiogenesis and direct antiproliferative effects on certain tumor cell types. Sunitinib resulted in tumor shrinkage in 80% of patients who had failed treatment with Bevacizumab and 13% of patients demonstrated an objective Response Evaluation Criteria in solid Tumors (RECIST) in a study presented at the 2006 American Society of Clinical Oncology (ASCO) meeting. We report the first published pathological evidence of sunitinib's effect on recurrent renal cell carcinoma. This was seen in a patient with renal cell carcinoma who developed a renal fossa recurrence 2 years following radical nephrectomy. Tumor shrinkage was evident in the nephrectomy bed after treatment with sunitinib. The pathology of the resected retroperitoneal mass and its implications are discussed.     

Treatment of metastatic renal cell carcinoma to the brain: a report of long-term survival following multimodal treatment and sequential use of targeted agents

The prognosis of renal cell carcinoma with brain metastasis is generally poor. Here we report a case of a 56-year-old man with metastatic renal cell carcinoma to the brain who underwent metastasectomy, cytoreductive nephrectomy, and whole brain radiotherapy. Thereafter, he received sunitinib, everolimus, and sorafenib sequentially for 11 months, 2 months, and 2 months, respectively. No tumor recurrence or progression of brain lesions has been reported in this patient for the past 16 months.     

An unusual case of transitional cell carcinoma of renal pelvis presenting with brain metastases

We report a rare case, who had presented with a constellation of neurological symptoms (due to multiple brain metastases), but without any urological symptoms, to the department of neurosurgery. The patient was managed with gamma knife stereotactic radiosurgery for the metastatic lesions. During an evaluation for primary, he was found to be having transitional cell carcinoma (TCC) of right renal pelvis, for which palliative radical nephroureterectomy was performed, following which he received four cycles of paclitaxel and carboplatin chemotherapy. The patient is alive with stable disease at 22-months follow-up.     

A huge renal cell carcinoma: Case report and literature review

In the current era, because of the prevalence of sonography, renal cell carcinoma usually can be detected in the early stages and a huge tumor is rarely encountered. Recently, we found a huge clear cell-type renal cell carcinoma that weighed approximately 2.7 kg, which is very rare.     

Patients with distant metastases from renal cell carcinoma can be accurately identified: external validation of a new nomogram

OBJECTIVE

To identify clinical variables that can accurately predict the presence of distant metastases in patients with renal cell carcinoma (RCC).

PATIENTS AND METHODS

Age, symptom classification, tumour size and the prevalence of distant metastases at diagnosis before nephrectomy were available for 5376 patients with pathologically confirmed RCC. The data of 2660 (49.5%) patients from 11 centres were used to develop a multivariable logistic regression model‐based nomogram predicting the individual probability of distant metastases. The remaining data from 2716 (50.5%) patients from three institutions were used for external validation.

RESULTS

In the development cohort, 269/2660 (10.1%) had distant metastases, vs 285/2716 (10.5%) in the external validation cohort. Symptom classification and tumour size were independent predictors of distant metastases in the development cohort; age was not an independent predictor. A nomogram based on symptom classification and tumour size was 85.2% accurate in predicting the individual probability of distant metastases in the external validation cohort.

CONCLUSION

Although distant metastases might be easily identifiable in some patients, their diagnosis might be a challenge in others. The current nomogram provides a simple, user‐friendly and, most importantly, an accurate tool aimed at predicting the probability of distant metastases in patients with RCC.     

舒尼替尼治疗晚期肾癌中血液学不良反应的诊治体会

目的 总结舒尼替尼治疗晚期转移性肾癌癌中患者血液学不良反应的诊断、分级和处理经验. 方法 转移性肾癌患者62例.男44例,女18例.年龄25～75岁.临床诊断均为晚期或不可手术的肾细胞癌,并至少有1处可测量的转移病灶.初始患者均采用舒尼替尼50 mg/d口服,用药4周,间歇2周的治疗方案.每个周期进行一次安全性评价,每2个周期进行一次疗效评价. 结果 62例患者中,出现血液学不良反应50例(80.6％),主要表现为血小板、白细胞降低和贫血,其中1～2度反应32例(51.6％),3～4度反应18例(29.0％).1～2度反应给予药物对症治疗;3～4度反应需要将舒尼替尼减量或停药,同时予对症处理.58例患者经过治疗后最终耐受舒尼替尼治疗.21例药物减量,其中9例(42.9％)为血液学不良反应所致. 结论 舒尼替尼对晚期转移性肾癌的病情控制有显著效果,血液学不良反应是用药后较常见的现象,合理、及时地处理血液学不良反应是获得满意疗效的保证.     

Treatment of bone metastases and local recurrence from renal cell carcinoma with immunochemotherapy and radiation

Summary Immunotherapies using interferons and/or interleukins are currently the treatment of choice for metastatic renal cell carcinoma (RCC). Bone metastases and non-resectable local recurrence are negative predictors for successful immunotherapy and signs of poor prognosis. The present study was designed to evaluate the effectiveness of combined immunochemotherapy (ICT) and radiation therapy (RT) for bone metastases or local recurrence from RCC in a prospective fashion. From September 1997 to September 1999, 20 patients with progressive RCC were treated with a combination of RT and ICT [s.c. interleukin-2a (IL-2), s.c. interferon alpha (IFN-) and i.v. 5-fluorouracil]. RT started in week 2 of ICT. The radiation field was limited to the symptomatic bone metastases (15 patients) or the local recurrence (five patients). The total dosages of the RT ranged between 45 and 50 Gy, administered in fractions of from 1.8 to 2 Gy daily. In case of objective response or stable disease, the patients received up to two further ICT courses. All patients had good pain relief. Three out of 20 achieved complete remission, three had a partial remission, nine were stable and five patients had progressive disease under the combined treatment. Median survival was 21 months, mean survival 24 months (range: 5–59 months). The side effects of the combined treatment are in the same range as with ICT alone (World Health Organisation grade 2 and 3). Of 20 patients, 19 had their pain medication reduced after treatment. The combination of ICT and RT is feasible. There is remarkable pain relief. Our data suggest that the combination of immunochemotherapy and radiation therapy may induce a synergistic antitumor effect for the treatment of bone metastases or local recurrence from RCC compared to data from the literature for ICT or RT alone.     

多房性囊性肾癌一例报告及文献复习

目的 提高多房性囊性肾癌的诊治水平.方法多房性囊性肾癌患者1例,男,49岁.体检B超偶然发现右肾下极多囊性肿物1个月.囊内无回声区,其间混杂低回声区;CT检查右肾下极见多囊性低密度病变,边界清楚、光整,内见薄壁分隔,增强扫描分隔可见强化;MRI检查示右肾下极多囊性病变,增强扫描囊壁可见强化.行右肾部分切除术,完整切除肿瘤.结果 病理报告:肾被膜下见多房状肿物,大小约3.0 cm×2.0 cm×2.0 cm,囊壁光滑,腔内含清亮的浆液性及血性液体,囊壁厚约0.1～0.2 cm,与肾周脂肪粘连.镜下多数囊腔内衬单层或复层立方状透明细胞,细胞核小而圆,位于细胞中央,无明显核仁;有的囊腔内衬扁平上皮细胞或无内衬上皮,偶见由透明细胞覆盖的小乳头;囊腔间隔由胶原纤维组成,部分间隔内可见灶状透明细胞,但未形成肉眼可见的结节.病理诊断:多房性囊性肾癌.术后随访20个月未见复发和转移.结论 多房性囊性肾癌是肾癌的一种罕见亚型,发病率低,是一种完全由囊腔构成的肿瘤;影像学检查可提供直接依据,确诊需依靠病理学检查;外科手术治疗预后良好.