Therapy on pulmonary metastasis of renal cell carcinoma

We reviewed the results of therapy on pulmonary metastasis of renal cell carcinoma performed in our hospital between 1979 and 1988. Eighty patients of renal cell carcinoma were treated during the period. Of those patients 13 (10 males and 3 females) had pulmonary metastasis and their ages were between 52 and 74 (average 61.6). The therapies we performed were surgical resection, cytotoxic chemotherapy, BRM (biological response modifier) therapy, hormone therapy and irradiation therapy. Four patients became tumor free by administration of medroxyprogesterone acetate, interferon-alpha, UFT (a compound combining tegafur and uracil) and surgical resection respectively. In 1 patient, administration of UFT resulted in partial remission. Cytotoxic chemotherapy using cisplatin, vinblastine and doxorubicin, and irradiation therapy were not effective. These findings suggest that BRM therapy, UFT therapy and hormone therapy are effective in eliminating pulmonary metastasis of renal cell carcinoma, particularly in the patients with excellent performance status whose original lesions had been resected.     

Clinical effect of UFT on urogenital tumors

Clinical study of UFT which was a mixture of FT and uracil, was conducted on 16 patients with urogenital malignancies. Seven patients had renal cell carcinoma, 5 patients had bladder cancer and 4 patients had prostatic cancer. UFT was continuously administrated at doses of 300 mg or 600 mg per day. One of the patients with renal cell carcinoma and 1 of the patients with bladder cancer showed a complete response, and 1 patient with each cancer showed a partial response, but none of the 4 patients with prostatic cancer responded. In total, complete or partial responses were obtained in 4 of the 16 patients, given an effective rate of 25.0%. Concerning side effects, 3 of the 16 patients complained of anorexia, nausea and vomiting, and stomatitis, but no hepatic or renal disorders, or marrow depression was observed.     

索拉非尼一线治疗晚期转移性肾癌的Ⅱ期临床研究

目的 评价索拉非尼一线治疗晚期转移性肾癌的疗效及安全性. 方法 转移性肾透明细胞癌患者12例,其中根治性肾切除术后出现复发或转移者11例,肿瘤侵及临近器官,原发灶无法手术切除者1例.均为初次治疗.12例均经病理检查证实为肾透明细胞癌.治疗方案:索拉非尼400 mg,每日2次,持续使用至疾病进展或出现不可耐受的不良反应. 结果 12例患者均可评价疗效.部分缓解3例,疾病稳定7例,疾病进展2例.客观反应率25%(3/12),疾病控制率83%(10/12).中位无进展生存期12(1～24)个月,中位生存期16(3～24)个月,6个月无进展生存率83%(10/12),1年生存率为50%(6/12).不良反应:食欲下降7例、脱发5例、乏力5例、腹泻5例、皮疹5例、手足皮肤反应4例、高血压4例、心悸3例、黏膜出血3例、声嘶1例、肾功能损害1例.通过对症治疗,不良反应基本可以控制并耐受. 结论 索拉非尼一线治疗转移性肾癌可取得较高的疾病控制率,无进展生存、总生存期均明显延长,不良反应可控制.     

Treatment of renal cell carcinoma with human lymphoblastoid interferon alpha and UFT in combination. A prospective multicenter trial

A cooperative study of combination of UFT (a compound of FT and Uracil) and human lymphoblastoid interferon (IFN-alpha) was conducted in the cases of metastatic renal cell cancer. IFN-alpha was administered over 3 times a week at a dose of 3 X 10(6) units in combination with UFT at a daily dose of 600 mg FT equivalent. Twenty-eight patients from 16 collaborating institutions were the subjects of the present study. The antitumor effects of the drugs were clinically evaluable in 25 cases according to the response criteria of Japan Society for Cancer Therapy. Complete responses and partial responses were observed in 3 and 2 cases, respectively, showing a response rate of 20 per cent. One complete responder had bone and liver metastases and has been alive for more than 2 years without any evidence of relapse. All of the other responders had lung metastasis. The survival durations of the other two complete responders were 716 days and 255 days. The two partial responders had been alive for more than 819 days and 471 days. The adverse effects of this combination therapy were minimal. Combination of a biological response modifier and a cancer chemotherapeutic agent seems to be a way to increase the treatment efficacy of renal cell cancer.     

Inhalation of lnterleukin-2 Combined with Subcutaneous Administration of Interferon for the Treatment of Pulmonary Metastases from Renal Cell Carcinoma

Background : lnterleukin-2 is the most promising antitumor agent for advanced renal cell carcinoma, but systemic immunotherapy with interleukin-2 might be limited because of inadequate efficacy and severe adverse effects. In this study, we treated 7 patients with lung metastases from renal cell carcinoma with topical application of interleukin-2 by inhalation.
Methods : Patients received 100,000 IU of interleukin-2 by inhalation 4 times a day and 9,000,000IU of interferon-alfa-2a subcutaneously for 5 consecutive days per week. They also received, by oral administration, 800 mg of cimetidine and 50 mg of indomethacin per day. After informed consent was obtained, the treatment started and the absence of any intolerable adverse effects was confirmed in a hospital. Then the treatment continued in an outpatient clinic for at least 3 months.
Results : Of 6 assessable patients, 5 responded to this treatment; 2 patients developed a partial response (33%) and 3 remained stable (67%). Disease progressed in the remaining patient. Therapy was discontinued in 1 patient because of his poor general condition. No severe adverse effects were observed, but pulmonary fibrosis probably associated with this treatment occurred in 1 patient. Conclusion: Although more cases and further evaluation are necessary to assess the significance and the safety of the inhalation of interleukin-2, this treatment is anticipated to be an option for selected patients with lung metastases from renal cell carcinoma.     

索拉非尼治疗晚期肾癌临床观察

目的 评价索拉非尼治疗晚期肾癌的疗效及安全性.方法 使用索拉非尼治疗晚期肾癌85例,其中采用索拉非尼400 mg,2次/d治疗70例;索拉非尼剂量递增(400 mg,2次/d,服药1～4周,600 mg,2次/d,服药1～4周,如患者能耐受则增量至800 mg,2次/d)治疗10例;索拉非尼400 mg,2次/d联合干扰素α(IFN-α)300万U,皮下注射,5 d/周治疗5例,直至肿瘤进展或出现不可耐受的不良反应.评价客观反应率、临床获益率、不良反应发生率.结果 可评价疗效病例80例,中位随访时间72(4～108)周.完全缓解(CR)1例(1.2%)、部分缓解(PR)1 7例(21.2%)、疾病稳定(SD)50例(62.5%)、疾病进展(PD)12例(15.0%).客观反应率(CR+PR)为22.5%(18/80),临床获益率(CR+PR+SD)为85.0%(68/80).索拉非尼剂量递增或索拉非尼联合IFN-α方案与索拉非尼单药方案相比差异均无统计学意义(P值分别为0.78和0.95).随访截止至2009年5月,因肿瘤进展死亡18例(22.5%),无疾病进展生存和总生存时间尚未达到.常见不良反应为手足皮肤反应44例(55.0%)、牙龈黏膜出血42例(52.5%)、腹泻32例(40.0%)、疲乏28例(35.0%)、食欲下降18例(22.5%)、黏膜溃疡16例(20.0%)、高血压12例(15.0%)、脱发12例(15.0%)等,但多为1～2级,经相应对症处理均可缓解.结论 索拉非尼单药、索拉非尼增量或索拉非尼联合IFN-α 3种方案治疗晚期肾癌的近期疗效良好,患者耐受性良好.     

Postoperative UFT Adjuvant and the Risk Factors for Recurrence in Renal Cell Carcinoma: A Long-Term Follow-Up Study

Background Radical nephrectomy is the standard therapy for low-stage renal cell carcinoma. However, recurrence sometimes develops even in patients who are considered to have undergone a curative resection of the primary tumor. The purpose of this study was to evaluate the usefulness of UFT (a 1: 4 mixture of tegafur and uracil) adjuvant and the risk factors for recurrence in renal cell carcinoma.
Methods A prospective randomized trial was conducted to compare the use of long-term oral UFT adjuvant with nonadjuvant therapy after a radical nephrectomy for Robson stage I or II renal cell carcinoma. A multivariate analysis was also performed to estimate the risk factors for recurrence.
Results A total of 71 patients were entered into this study, and 66 were evaluable (33 for each group). There was no significant difference in patient characteristics between the 2 groups. The nonrecurrence rate at 5 years after a radical nephrectomy was 80.5% and 77.1% in the UFT adjuvant group and the nonadjuvant group, respectively, with a median follow-up of 112.9 months; the difference was not significant. The toxicity of UFT was generally mild and tolerable. The tumor grade was found to be an important factor influencing recurrence.
Conclusion UFT cannot be universally recommended as an adjuvant therapy for radical nephrectomy in all patients with low-stage renal cell carcinoma.     

索拉非尼联合干扰素α一线治疗晚期肾癌Ⅳ期临床试验中期分析

目的 观察索拉非尼联合干扰素α(IFN-α)作为一线方案治疗晚期肾癌的疗效与安全性.方法 本研究为多中心、非随机Ⅳ期临床试验.入组初治的晚期肾癌137例.男102例,女35例.中位年龄56(18～81)岁.索拉非尼400 mg口服,2次/d;IFN-α 300万U,皮下注射,5次/周(d1～5),持续治疗,直至患者不能耐受或出现疾病进展.评价客观反应率、临床获益率、不良反应发生率.结果 完全缓解2例(1.5%),部分缓解43例(31.4%),客观有效率32.8%(45/137).截止到2009年2月底,中位随访时间11.9个月,疾病进展25例,中位无疾病进展时间尚未达到.常见不良反应为手足皮肤反应66例(48.2%)、脱发32例(23.4%)、皮疹28例(20.4%)、腹泻27例(19.7%)、发热23例(16.8%)、疲乏14例(10.2%),其中3～4级手足皮肤反应12例(8.8%).结论 索拉非尼联合IFN-α治疗晚期肾癌有效率32.8%,安全性良好,可作为晚期肾癌的一线治疗方案.     

Comparative clinical study of single and combination therapy of human lymphoblastoid interferon (HLBI) with 5-FU in the treatment of advanced renal cell carcinoma

A clinical trial using human lymphoblastoid interferon (HLBI) was done on patients with advanced renal cell carcinoma to compare the efficacy of monotherapy with that of combined administration with a 5-fluorouracil (FU) agent. A total of 24 patients with definitely diagnosed advanced renal cell carcinoma were enrolled in either of the HLBI treatments. Principally, the daily intramuscular injection of 3 million units of HLBI was done for 4 consecutive days and thereafter followed by twice of weekly injections. The combined agent used in the present study was 300 or 600 mg of 5-fluorouracil agent given orally. The efficacy of HLBI was evaluated according to direct assessment standard of chemotherapy to a solid tumor expelled by the committee of Japanese health and welfare ministry. Of 11 patients who received monotherapy, 3 had a partial response rate of 27.3 percent. While only one of 13 patients having received combined HLBI administration with oral 5-FU tablets showed a partial response with a response rate of 7.7 percent. A total of 4 patients partially responded to either HLBI treatment with a subsequent response of 16.7 percent. Partial response implied reduction of lung metastatic foci in 3 patients and primary lesion in one patient. There was observed untoward fever-up in all patients with HLBI injections which was relieved with acquired tachyphylaxis owing to repeated injections. Otherwise minimal adverse effects were temporary elevation of liver transaminase in 4 and leucopenia in 2 patients during the HLBI treatment both of which eventually returned to the normal level without discontinuation of HLBI therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of pulmonary metastasis from renal cell carcinoma with complete response to interferon-alpha and tegafur/uracil (UFT) but possibly UFT-induced liver dysfunction and leukoencephalopathy-like symptoms]

A 61-year-old man presented with gross hematuria. He underwent left radical nephrectomy under a diagnosis of left renal cell carcinoma without distant metastasis, but bilateral multiple pulmonary metastases appeared 2.5 months after the operation. Though the metastases responded well to combination therapy of interferon-alpha and a 1:4 mixture of tegafur and uracil (UFT), the side effects of liver dysfunction and leukoencephalopathy-like symptoms due to UFT appeared 7 months after the beginning of the chemotherapy. These side effects were improved after the cessation of UFT administration.     

Efficacy and safety of apatinib monotherapy in metastatic renal cell carcinoma (mRCC) patients: A single-arm observational study

BackgroundAntiangiogenic treatments play an important role in the therapeutic strategy for metastatic renal cell carcinoma. Apatinib is an oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. We aimed to assess the efficacy and safety of apatinib therapy in metastatic renal cell carcinoma patients.MethodsBetween January 2018 and November 2018, we enrolled 53 metastatic renal cell carcinoma patients. Apatinib was administered at an initial dose of 500 mg once daily. The disease control rate, objective response rate, progression-free survival, and adverse events were reviewed and evaluated.FindingsAmong the 53 patients, 14 achieved partial response and 31 achieved stable disease. Thus, the disease control rate was 84.9% and the objective response rate was 26.4%. The median progression-free survival was 11.2 months (95% confidence interval: 9.884–12.574). Most of the adverse events (AEs) were at grade 1 or 2, and the main grade 3 AEs were hypertension (5.7%), anemia (3.8%), and thrombocytopenia (3.8%).InterpretationApatinib showed promising efficacy and manageable toxicity in metastatic renal cell carcinoma patients, giving potent evidence to conduct further clinical trials.     

Lysis of autologous tumor cells by peripheral blood lymphocytes treated with IFN-alpha in patients with renal cell carcinoma]

Immunotherapy, consisting mainly of interferon (IFN) therapy, has been used to treat renal cell carcinoma refractory to radiotherapy and chemotherapy ever since IFN was reported to be effective against renal cell carcinoma in 1982. The efficacy of IFN is low, with the response rate being only about 20% and the method and duration of its administration have yet to be established. Using viable tumor cells obtained at nephrectomy, we discovered that IFN-alpha induced killer cells have a cytocidal effect on autologous renal cell carcinoma cells and that assaying the cellular immunity of the peripheral blood lymphocytes of 25 patients with renal cell carcinoma, using ACHN derived from human renal cell carcinoma as the target cells, is useful as a monitoring method during IFN-alpha therapy. Augmentation of the cytotoxicity of peripheral blood lymphocytes in response to administration of IFN-alpha was observed in all 25 cases. Cytotoxicity was activated to 5-426 LU compared with the control value of 1 LU or less before IFN therapy, when autologous renal cell carcinoma cells were used as the target cells. Cytotoxicity for ACHN cells in the control value before IFN-alpha therapy and 4 weeks after the institution of IFN-alpha administration and autologous tumor lysis in the induction assay were more strongly correlated than in the case of K562 cells. A strong correlation was also found between cytotoxicity for ACHN cells in the induction assay and 4 weeks after the institution of IFN-alpha administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

舒尼替尼治疗转移性肾癌的初步评价

目的 评价舒尼替尼治疗转移性肾癌的疗效和安全性. 方法转移性肾癌患者31例.男23例,女8例.中位年龄55(25～75)岁.31例中行原发肿瘤切除30例,仅行活检术1例,病理证实为肾细胞癌,并至少有1处可测量的转移病灶.初始患者均口服舒尼替尼50 mg/d,用药4周、间歇2周为1个周期,每2个周期行CT扫描以评价疗效. 结果全组可评价疗效24例,无完全缓解病例,部分缓解5例、疾病稳定15例、疾病进展4例,其中死亡1例.中断治疗4例,其中因高龄、全身情况差、不能耐受服药1例,因经济困难停药2例,因肝功能损害停药1例.3例因治疗时间短而未评价.全组客观反应率21%(5/24),疾病控制率83%(20/24),中位无疾病进展生存时间11个月,1年无进展生存率80%.常见不良反应是手足皮肤反应、腹泻、食欲差、口腔炎、出血倾向和血液学毒性,分别通过外敷、口服药物和补液治疗得到及制. 结论舒尼替尼对转移性肾癌的病情控制有显著效果,也存在一定不良反应,通过及时干预和处理,患者大多可以耐受其不良反应.     

Combination chemotherapy of human renal cell carcinoma in athymic nude mice with human lymphoblastoid interferon (HLBI) and UFT, 5-Fu

The effectiveness of interferon alpha (HLBI) for nude mouse transplantable human renal cell carcinoma 72nd general meeting, in combination with UFT and 5-Fu, was examined using, 1 x 10(7) IU/kg, 2 x 10(7) IU/kg HLBI; 25 mg/kg 5-Fu; and 10 mg/kg, 20 mg/kg UFT, administered for 10 consecutive days. The ratio of relative mean tumor weight of treated group to control group was under 42% for the combination of 25 mg/kg (I.P.) 5-Fu, 20 mg/kg UFT, and HLBI and the effect was particularly clear for the combination with 2 x 10(7) IU/kg which indicated a grade IIA histologic classification. In comparison with the control groups only UFT (20 mg/kg) and HLBI (2 x 10(7) IU/kg) showed significant inhibition when administered alone. Although none of the drugs had an inhibitory effect when administered alone, in combined use they showed a strong antitumor effect which was more than synergistic. Orally administered 5-Fu showed a statistically significant difference only in the combination with 2 x 10(7) IU/kg HLBI. Furthermore, the concentration of 5-Fu in the tumor tissue was not affected by the route of administration or drug combination, whereas that in the serum was below the limit of detection in the intraperitoneally administered cases, 0.0096 +/- 0.0079 microgram/ml, lower than the value for orally administered cases. The 5-Fu concentration was 0.026 +/- 0.012 microgram/ml for orally administered UFT which was significantly higher than the value obtained for orally administered 5-Fu. Thus, combination therapy of HLBI and UFT for renal cell carcinoma is expected to be clinically useful.     

Clinical efficacy of recombinant interleukin-2 for renal cell carcinoma and the effect of blood transfusion upon the immune response of these patients

We studied the efficacy and safety of recombinant interleukin-2 (rIL-2: S-6820) for the treatment of renal cell carcinoma as well as the effect of blood transfusion upon the immune response of these patients. Among 14 cases of renal cell carcinoma treated by i.v. infusion of rIL-2, a partial response (PR) was achieved in one patient, 10 patients had no change, and in 3 had the disease progressed. The overall efficacy rate was 7.1%. However, the rate increased to 12.5% in cases with pulmonary metastases and to 14.3% in cases without any blood transfusion within a year before treatment with rIL-2. No severe side effects were observed, except for central nervous system disturbance in one case. During the rIL-2 therapy, LAK activity was suppressed in the transfused patients. On the other hand, NK activity was augmented in transfused patients to the same degree as in non-transfused cases. No significant changes of lymphocyte count and the subsets of peripheral blood lymphocytes were observed in either group treated with rIL-2. Anemia and radical nephrectomy did not affect the immune response in these patient. Thus, it appeared that blood transfusion altered the immune response in patients treated with rIL-2. However, it could not be concluded that transfusion definitely had an adverse effect on the clinical efficacy of rIL-2 for renal cell carcinoma.     

Phase II trial of weekly intravenous gemcitabine administration with interferon and interleukin-2 immunotherapy for metastatic renal cell cancer

PURPOSE: Since metastatic renal cell carcinoma has a poor prognosis and treatment strategies, including hormone therapy, chemotherapy and immunotherapy, have little impact on the quality of life and global survival statistics, new interest has recently focused on the combination of immuno-chemotherapy using pyrimidine analogues, such as gemcitabine. MATERIALS AND METHODS: In a phase II study 16 patients with metastatic renal cell carcinoma were treated with 1,000 mg./m. gemcitabine intravenously on days 1, 8, 15 and 28 for 6 months, 3 MU (1 MU = 1 x 10(6) IU) interferon (IFN)-alpha intramuscularly 3 times a week and 4.5 million IU interleukin (IL)-2 subcutaneously daily for 5 days a week for 2 consecutive weeks every month for 6 months. Responding and nonprogressing cases were maintained on immunotherapy consisting of IFN-alpha and IL-2 for further 6 months. RESULTS: In 15 evaluable patients overall response rate (1 complete response plus 3 partial response) was 28% while stable disease was achieved in 7 (47%). Median survival duration was 20 months (range, 9 to 26+) and median time to tumor progression was 14 months (6 to 26+). The complete response lasted 24+ months and partial response lasted 16 months. The regimen was well tolerated with only 1 case of neutropenia (WHO grade 3), while anorexia, fatigue and flu-like symptoms were the most common toxicity problems but were never greater than grade 2. CONCLUSIONS: Despite the small sample size, this study demonstrates that gemcitabine combined with standard doses of IFN-alpha and low doses of IL-2 is effective treatment for metastatic renal cell carcinoma. This biotherapy was well tolerated and resulted in an optimum objective response and relatively long-term survival.     

Complete remission of advanced renal cell carcinoma by chemotherapy and surgical treatment: a case report

A rare case of metastatic renal cell carcinoma which represented complete remission by chemotherapy and surgical treatment is presented. A 59-year-old female was admitted to our hospital because of general fatigue, weight loss and appetite loss. The diagnosis of right renal tumor metastasized to both lungs and extending into the inferior vena cava was made by radiographic findings. Because of very poor general condition the first choice of treatment was chemotherapy with cisdichlorodiamine platinum, adriamycin, cyclophosphamide, 1-(2-tetrahydrofuryl)-5-fluorouracil) (UFT), and OK432. Five months after the beginning of chemotherapy both lung coin lesions disappeared completely, and radical nephrectomy including venacavotomy and tumor thrombectomy was performed. At present, 6 months after the radical nephrectomy, she is free from the disease and complete remission has been obtained by oral administration of 400 mg/day UFT and 5.0 KE OK432 intracutaneous injection every week.     

舒尼替尼治疗转移性肾癌的疗效和安全性分析:单中心37例总结

目的 评价舒尼替尼治疗转移性肾细胞癌的疗效和安全性.方法 2008年6月至2010年4月37例转移性肾细胞癌患者接受舒尼替尼治疗.其中男28例,女9例.年龄17～74岁,中位年龄52岁.行根治性肾切除手术33例,肾穿刺活检3例,腋窝转移淋巴结穿刺活检1例.vonHippel-Lindau综合征患者2例.肾透明细胞癌36例,其中伴颗粒细胞成分1例、伴肉瘤样分化4例,肾乳头状细胞癌1例.一线治疗30例,细胞因子或索拉非尼治疗进展后二线治疗7例.其中34例采用4/2方案,即口服舒尼替尼50.0 mg/d 4周,停用2周,6周为1个周期;3例予口服37.5 mg/d持续治疗,直至疾病进展或者出现不可耐受的不良反应.结果 中位随访时间12个月(8个周期).34例患者治疗2周期以上,可进行疗效评估.根据RECIST标准评价最佳疗效,部分缓解9例(26.5%),疾病稳定24例(70.6%),疾病进展1例(2.9%).客观反应率26.5%,疾病控制率97.1%.1年生存率95.8%(23/24),1年无进展生存率62.5%(15/24).主要不良反应包括血小板减少30例(81.1%)、甲状腺功能异常18/22例(81.8%)、手足反应27例(73.0%),白细胞减少23例(62.2%)、高血压18例(48.6%)等.大多数不良反应为1～2级,3级以上不良反应包括血小板降低8例(21.6%)、甲状腺功能异常4/22例(18.2%)、手足反应4例(10.8%)、血磷降低4例(10.8%)和腹泻2例(5.4%)等.10例(27.0%)在治疗过程中减量或停药,1例因严重乏力不能耐受终止治疗.通过对症支持,减量或停药,不良反应可控制并耐受.结论 舒尼替尼一线及二线治疗晚期转移性肾细胞癌可取得较高的疾病控制率,不良反应发生率多数轻而易耐受,严重不良反应较少且可控.

Abstract：

Objective To evaluate the efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma (RCC). Methods A total of 37 patients with metastatic RCC were treated with between June 2008 and April 2010, including 28 males and 9 females. The median age was 52 (17-74) years. All patients received a pathologic diagnosis of RCC, which consisted of 1 papillary cell carcinoma and 36 clear cell carcinomas, 4 of which accompanied with partial sarcoma differentiation. Thirty cases were treated with first line therapy and 7 cases showed progression on first-line cytokine or sorafinib therapy. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients, while another 3 patients received 37. 5 mg Qd continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. Results The median follow up was 12 months (8 cycles),range 1.5-19. 5 months (1-13 cycles). 26.5% (9/34) patients achieved partial responses, 70.6%(24/34) patients demonstrated stable disease over≥3 months and 1 (2. 9%) patient developed progressive disease. The objective response rate was 26.5%, and the disease control rate was 97. 1%.The 12 months' overall survival rate was 95.8% (23/24), and 12 months' progression-free survival rate was 62.5 % (15/24). The most common treatment-related adverse events were thrombocytopenia (30 cases, 81.1%), thyroid dysfunction (18/22, 81.8%) ,hand-foot syndrome (27 cases, 73.0%),neutropenia (23 cases, 62.2%) and hypertension (18 cases, 48.6%). The major grade 3 adverse events included thrombocytopenia (8 cases, 21.6%), hand-foot syndrome (4 cases, 10.8%) and diarrhea (2 cases, 5. 4%). Most adverse events were ameliorated by treatment interruption. Ten (27.0%) patients had dose decrement or drug discontinuation and 1 patient quit the treatment for intolerable fatigue. Conclusion The efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic RCC.     

索拉非尼增量治疗转移性肾癌的初步报告

目的 评价索拉非尼增量治疗转移性肾癌的疗效及安全性. 方法 16例复治的转移性肾透明细胞癌患者,中位年龄53(37～71)岁.男女比例3:1.既往均接受过肾癌根治术和至少1个方案的全身治疗,存在至少1个单径可测病灶,均服用索拉非尼,从800 mg/d逐渐增量至1200或1600 mg/d,直至不能耐受或病情进展,评价近期疗效、不良反应和无进展生存期. 结果 16例患者中位随访时间11(9～16)个月.客观有效(完全缓解加部分缓解)7例,临床受益(完全缓解加部分缓解加病灶稳定)13例.严重不良反应(≥3级)主要表现为手足皮肤反应25%(4/16)、黏膜炎19%(3/16)、腹泻19%(3/16)、高血压12%(2/16)和骨髓抑制12%(2/16),经剂量调整和一般对症治疗后短期内症状可消失或减轻到1～2级. 结论 索拉非尼增量治疗晚期肾癌可获较高的客观反应率,不良反应可控制,能延长高危患者的无进展生存期.     

Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial

BACKGROUND: The purpose of this study is to evaluate the efficacy of postoperative adjuvant chemotherapy using uracil and tegafur (UFT) for colorectal cancer. METHODS: In a multicenter trial among 43 institutions for patients who underwent curative resection of Dukes' B or C colorectal cancer, a surgery alone group (control group) and a treatment group (UFT group) to which UFT was administered at 400 mg/day for 2 years following surgery were compared. A total of 320 patients were registered between March 1991 and April 1994, and 289 of these patients were analyzed as a full-analysis set. RESULTS: The 5-year disease-free survival rate was 75.7% in the UFT group and 60.1% in the control group, respectively, and the stratified log-rank test showed the statistical significance ( P=0.0081). This difference was marked in rectal cancer ( P=0.0016) and, in particular, the local recurrence was reduced. No significant difference was observed in the 5-year survival rate. The incidence of adverse reactions on administration of UFT was low, and there was no serious adverse reaction. CONCLUSION: It is suggested that the consecutive administration of UFT at 400 mg/day was an effective and highly safe therapeutic method as postoperative adjuvant chemotherapy for rectal cancer.