输注经照射的HLA部分相合的异基因单个核细胞治疗晚期肾细胞癌

背景与目的：肾细胞癌是一种对免疫治疗敏感的肿瘤,包括了非清髓性异基因移植。然而由于严重的毒性,许多转移性肾细胞癌并不适合非清髓性异基因移植。这促使了其他一些新的异基因免疫治疗的发展。本研究评价输注经照射的HLA部分相合的异基因单个核细胞治疗晚期肾细胞癌的有效性和安全性。方法：选择经病理证实的晚期肾细胞癌患者,予输注经照射的HLA部分相合的异基因单个核细胞。每2个月输注1次,治疗有效或稳定者继续输注,直至疾病进展或出现不能耐受的不良反应或患者（或供者）拒绝继续使用。结果：8例患者进入本研究。6例患者每次输注后每日口服沙利度胺100mg至300mg两个月,1例达到持久的完全缓解（CR）,5例稳定（SD）,2例进展（PD）。8例患者的中位疾病无进展时间为292d,中位生存时间为879d以上。毒性反应轻微。结论：输注经照射的HLA部分相合的异基因单个核细胞治疗晚期肾细胞癌有了一定疗效,值得进一步研究。     

Phase II trial of thalidomide in renal-cell carcinoma.

BACKGROUND: Thalidomide has been reported to yield anti-tumor activity in cancer. We performed a phase II trial of this drug in patients with metastatic renal cell carcinoma to determine its efficacy. PATIENTS AND METHODS: Patients with proven metastatic renal cell cancer, measurable progressive disease and a performance status of 0-2 were enrolled in this study. Thalidomide was given daily at a starting dose of 400 mg, followed by a 400 mg increment to 800 mg and then to 1200 mg with 6-12 weeks at each dose level. The response rate at 6 months was the primary end point. Toxicity, overall survival, tumor vascularization depicted on color Doppler ultrasonography and serum vascular endothelial growth factor, basic fibroblast growth factor, interleukin-12 and tumor necrosis factor-alpha levels were secondary end points. RESULTS: Forty patients were enrolled. Two partial responses were observed (5%) and disease remained stable in nine patients after 6 months. Median survival was 10 months. Toxicity was high, with frequent manifestations of fatigue, constipation and lethargy. The incidence of neuropathy detected on electromyography (EMG) attained 70% at 6 months, and 100% in patients on thalidomide for 12 months. Nine patients developed venous thromboembolism during the first 12 weeks of treatment, and three of them experienced pulmonary embolism. One unexpected (and unexplained) death occurred. CONCLUSIONS: Despite undisputed, albeit marginal, activity in renal cell cancer, high-dose thalidomide cannot be recommended using this schedule since the level of toxicity is high.     

Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma.

PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.     

Lipomatous meningioma of the brain harboring metastatic renal-cell carcinoma: A case report

A 70-year-old woman presented with mild left hemiparesis and intermittent global headache. Magnetic resonance imaging showed a 6×6×6-cm tumor in the right frontal lobe, and abdominal computed tomography revealed a 8×8×7-cm mass lesion in the left kidney. Magnetic resonance imaging showed that the brain tumor consisted of a central hyperintense cystic component and an outer hypointense component. The patient underwent total surgical excision of the intracranial mass. Histological and immunohistochemical examination showed that the lesion was a lipomatous meningioma harboring metastatic renal-cell carcinoma. Both of these tumors are rare. The magnetic resonance imaging findings are indicative of but not specific to meningioma harboring metastatic tumor.     

沙利度胺联合介入治疗中晚期肝癌疗效观察

目的评价沙利度胺联合介入治疗中晚期肝癌的临床疗效。方法89例中晚期肝癌患者随机分为口服沙利度胺 肝动脉灌注栓塞化疗组(TLD TACE组)和单纯肝动脉灌注栓塞化疗组(TACE组)。结果TLD TACE组近期有效率、1年局控率分别为57.5%和65.0%,明显高于TA-CE组的34.5%和43.1%。不良反应以腹胀、便秘、头晕、嗜睡最常见,患者可耐受。结论沙利度胺联合介入治疗中晚期肝癌疗效明显,不良反应轻,具有一定的临床应用价值。     

卡瑞利珠单抗联合沙利度胺治疗晚期肝细胞癌的疗效及安全性

目的:评估卡瑞利珠单抗联合沙利度胺在晚期肝细胞癌患者中的疗效和安全性。方法:收集2019年7月至2020年7月既往全身治疗进展或不耐受的晚期肝细胞癌患者24例,给予卡瑞利珠单抗200 mg静脉滴注,每3周给药1次;沙利度胺100 mg起始,1周后增至200 mg,每晚1次口服。评价疗效及安全性。结果:共24例患者纳入研究,其中1例完全缓解,8例部分缓解,9例疾病稳定,4例疾病进展,客观缓解率为37.5%（9/24）,疾病控制率为75.0%（18/24）。2例患者在随访期间死亡,死亡原因为疾病进展导致的多器官衰竭,中位PFS为6.5个月（95%CI,5.15~7.85）。最常见的不良反应是反应性皮肤毛细血管增生症（41.7%）、血小板减少（33.4%）、γ-谷氨酰转肽酶升高（25.0%）、白细胞减少（20.8%）和转氨酶升高（29.2%）,1例3级血小板减少事件,2例3级转氨酶升高事件,未发现4级及以上的不良反应。结论:卡瑞利珠单抗联合沙利度胺在晚期肝细胞癌患者中显示出一定的疗效和可控的安全性。对于既往全身治疗进展或不耐受的晚期肝细胞癌患者来说,这可能代表了一种新的治疗选择。     

Mitomycin-C and metronidazole in the treatment of advanced renal-cell carcinoma

Fifteen patients with advanced renal-cell carcinoma were treated with the combination of mitomycin-C 14-20 mg/m2 i.v. every 7 weeks and metronidazole 1,500 mg/m2 p.o. 12 and 1 h before and 6 and 24 h after the mitomycin-C. Of 12 patients evaluable for response, three (25%) responded with partial remissions. Myelosuppression did not appear to be increased over that seen with mitomycin-C alone. Pulmonary toxicity occurred in three patients and was fatal in two. The incidence of pulmonary toxicity was probably increased over that seen with mitomycin-C alone. Renal toxicity was also seen. Based on this small study, it was our feeling that this dose-schedule of metronidazole did not appear to result in enough of an augmentation of the efficacy of mitomycin-C against renal-cell carcinoma to justify the incidence of serious toxicity.     

Phase II trial of titanocene dichloride in advanced renal-cell carcinoma

Titanocene dichloride was capable of inhibiting the growth of different types of human tumors in vitro. A total of 14 patients with metastatic renal-cell carcinoma (RCC) received 270 mg/m² titanocene dichloride every 3 weeks for 6 weeks. Although the toxicities and side effects encountered were mild to moderate, no partial or complete response was detectable. In conclusion, titanocene dichloride has no advantage in the therapy of RCC. Received: 18 February 1998 / Accepted: 23 April 1998     

Partial response to lonidamine of advanced bladder carcinoma: a case report

A 76 year old woman presented with locally advanced papillary transitional cell carcinoma. The patient had elsewhere had trans-urethral resection and radiotherapy and declined salvage cystectomy. She was treated with Lonidamine (150 mg X 3/day p.o. Repeat CT scan after 8 months showed partial remission. This response was unchanged after 28 months Lonidamine therapy.     

沙利度胺联合肝动脉化疗栓塞治疗中晚期肝癌的临床研究

探讨沙利度胺(TLD)联合肝动脉化疗栓塞(TACE)治疗中晚期原发性肝癌的临床疗效及不良反应。120例患者随机分为观察组和对照组各60例,观察组在TACE基础上加口服TLD,对照组不用TLD。近期疗效显示,观察组肿瘤完全缓解(CR)8例,部分缓解(PR)45例,无变化(SD)4例,进展(PD)3例,总有效率为88.3%,对照组为65.0%(P=0.037)。两组未见严重不良反应发生。随访3年,观察组1、2和3年生存率分别为75.0%、69.8%和55.2%;对照组为48.3%、42.9%和33.3%,P<0.05。初步研究结果提示,应用TLD联合TACE治疗中晚期原发性肝癌疗效明显,不良反应轻,具有较好的临床应用价值。     

Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report

Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well-tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules.     

Stereotactic ablative radiotherapy with CyberKnife for advanced thymic carcinoma: a case report

Thymic carcinoma is a rare but lethal mediastinal cancer. The optimal treatment for advanced thymic carcinoma is not yet established. This report is the first known of stereotactic ablative radiotherapy (sabr) with CyberKnife (Accuray, Sunnyvale, CA, U.S.A.) as definitive therapy for thymic carcinoma.The patient, a 70-year-old woman with thymic carcinoma, invasion into neighboring organs, and pleural metastases—underwent CyberKnife sabr at 40 Gy in 5 fractions for two lesions, one in the thymus and one in the right paraspinal pleura. After 61 months of observation, a partial response was observed in the irradiated fields. However, disease progression in the non-irradiated pleura was noted. The patient underwent salvage CyberKnife sabr for the four initially nonirradiated pleural lesions. Computed tomography images obtained 10 months after the salvage therapy revealed a partial response.The patient is living, with progression-free irradiated lesions and no radiation-related toxicity. CyberKnife sabr is feasible for patients who are unable to undergo either surgery or conventionally fractionated radiation therapy.     

Successfully resected advanced gastric carcinoma after combined chemotherapy of TS-1 plus CDDP--a case report

A 66-year-old man complained of epigastralgia and a close examination was done. A type 3 gastric carcinoma was found. The tumor invading the pancreas and swelling lymphnodes around the stomach were confirmed according to abdominal CT. We considered it difficult to resect the tumor completely, and so we used combined chemotherapy of TS-1 plus CDDP. TS-1 was taken at 120 mg/day for 28 days followed by 14 days rest. CDDP was injected at 140 mg on day 8. Because the tumor in the stomach changed to scar and swelling lymphnodes diminished after two courses of therapy, total gastrectomy was done. After operation, combined chemotherapy of LV and 5-FU resulted in no recurrence to date. Although combined chemotherapy of TS-1 plus CDDP is effective for advanced gastric carcinoma, the number of days TS-1 is taken and the duration of the preoperative chemotherapy must be investigated in forthcoming study.     

重组人血管内皮抑素联合GC方案治疗晚期非小细胞肺癌1例报道

A 43-year-old female with a 3-month history of paroxysmal irritating cough presented progressive chest tightness and shortness of breath. Laboratory data showed elevated carcino-embryonic antigen (CEA). Further imaging studies revealed a soft tissue mass shadow was in right middle lobe lung with mediastinal and sub-carinal lymph nodes enlarged. Biopsy diagnosis: moderately and poorly differentiated adenocarcinoma of the lung. Clinical diagnosis: central non-small cell lung cancer (NSCLC) of right middle lobe (C_IVT₄N₂M₁), lung adenocarcinoma G2-3, malignant pleural effusion, pericardial effusion, hilar and mediastina lymph node metastases. After 4 cycles of endostar plus GC therapy, imaging studies revealed showed soft tissue mass in right middle lobe disappeared, and evaluation of short-term result was complete remission (CR). PFS has been seven months till now. Therefore, this report provided strong evidence that endostatin combined GC treatment for advanced NSCLC is safe and effective, which can prolong survival and improve quality of life.     

拓僖联合栓塞治疗中晚期原发性肝癌57例疗效分析

目的观察拓僖(HCPT,羟基喜树碱冻干粉针)为主的灌注化疗联合碘油栓塞治疗原发性中晚期原发性肝癌(PHC)的疗效和毒副作用.方法采用HCPT加氟尿嘧啶(5-Fu)、吡柔比星(THP)肝动脉灌注联合碘油(LP)肝动脉栓塞的化疗栓塞治疗方案,治疗中晚期原发性肝癌患者57例.结果 57例患者共接受化疗栓塞112次.部分缓解(PR)17例,稳定(NC)26例,进展(PD)14例,生存率6个月为81.8%,1年为54.5%,2年为22.7%.除进展病例外,患者临床症状(食欲减退、乏力、肝区疼痛等)均有不同程度改善.不良反应主要表现为发热、肝区疼痛、肝功波动、消化道症状和轻度骨髓抑制.在严重肝硬化基础上并发肝癌的患者肝动脉化疗栓塞后恢复缓慢.结论以HCPT为主灌注化疗联合肝动脉栓塞方案治疗中晚期肝癌,有可能延长患者生存期,提高生存质量,副作用小,但对于合并肝硬化的患者需要同时加强保肝治疗.