磁导向载体阿霉素介入治疗原发性肝癌的临床研究

目的：观察磁导向载体阿霉素(MTC-DOX)肝动脉介入治疗原发性肝癌的有效性和安全性。方法：将Seldinger导管超选择插入肿瘤供血肝动脉，以脉冲给药的方式注入MTC-DOX，21天为一周期，连续用药2周期以上按照WHO标准进行评价。结果：不能手术的原发性肝癌患共11例入组，10例可以评价疗效，治疗后NC7例，PD3例，中位肿瘤进展时间(TTP)为182天，有3例临床症状减轻，有4例生活质量改善，1年生存率达到54．5％；11例可以评价毒性，毒副反应均较轻，主要为轻中度的肝区疼痛和发热，少数患有胃肠道反应和一过性转氨酶升高。结论：采用磁导向载体阿霉素介入治疗原发性肝癌靶向性特别好，疗效明显，同时毒性反应轻微，值得进一步研究。     

术前动脉灌注化疗结合手术治疗直肠癌疗效分析

目的 :总结和分析直肠癌术前介入灌注化疗 (Pre operativeArteraInfusionChemotherapy ,PAIC)的疗效及其优点 ,探讨直肠癌综合治疗的远期疗效。方法 :应用Seldinger方法经皮右侧股动脉穿刺 ,选择肠系膜下动脉或骼内动脉造影确定肿瘤位置后 ,注入化疗药物。术后一周进行直肠癌根治术。术后采用 5 氟尿嘧啶加甲酰四氢叶酸钙进行 6个疗程的化疗。以同期未行介入灌注治疗而手术的直肠癌患者作为对照组。结果 :PAIC组大多数患者症状、体征减轻 ,肿块缩小。介入灌注化疗前后病理检查发现肿瘤细胞有变性坏死 ,细胞核变性 ,胞浆凝固 ,间质炎细胞浸润及纤维增生等不同程度的改变。术后五年生存率 75 0 0 % ,对照组为 4 5 2 4 % ,对比差异有显著性意义 (P <0 0 5 )。结论 :术前介入灌注化疗作为直肠癌新辅助化疗方法之一是有效、安全的 ,并能提高直肠癌患者的术后长期生存时间。     

Multimodal therapy with intravenous biweekly leucovorin, 5-fluorouracil and irinotecan combined with hepatic arterial infusion pirarubicin in non-resectable hepatic metastases from colorectal cancer (a European Association for Research in Oncology trial).

BACKGROUND: The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter. RESULTS: The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months. CONCLUSION: The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation.     

手术加皮下埋藏腹腔化疗泵联合化疗治疗晚期上皮性卵巢癌的疗效观察

目的：对晚期上皮性卵巢癌患者行手术及术中皮下埋藏腹腔化疗泵联合化疗，并对其疗效进行评价，以期对治疗提供帮助。方法：1995年8月～1997年8月收治的卵巢癌患者中24例行手术及术中皮下埋藏化疗泵，术后采用CAP方案联合化疗。顺铂50～70mg／m^2腹腔灌注，阿霉素40～60mg／m^2、环磷酰胺600～800mg／m^2静脉注射，平均4～5周为一疗程，总疗程6～12个。结果：Ⅲ期患者总有效率为77．8％；3年生存率50．0％，5年生存率25．0％。结论：彻底的手术加腹腔泵灌注腹腔化疗及静脉化疗是治疗晚期上皮性卵巢癌的有效途径，可提高患者的生活质量及生存率。     

Feasibility trial of high-dose 7-day continuous-infusion ifosfamide given on an outpatient basis

 High-dose ifosfamide (HD-IFX) has shown significant antitumor activity in advanced sarcoma and breast carcinoma. The use of uroprotective agents and the availability of ambulatory continuous-infusion pumps has allowed dose escalation in the administration of ifosfamide (IFX) on an outpatient schedule. We report the results of a phase II trial of IFX given at high doses to heavily pretreated patients. IFX was infused at 2 g/m² per day for a total of 7 days through a central venous access, with cycles being repeated every 21 days. Mesna was given concomitantly at equimolar doses. No hematopoietic support was used. A total of 27 heavily pretreated patients whose disease had progressed during conventional-dose chemotherapy were included (14 sarcomas, 10 breast carcinomas, and 3 bladder carcinomas). Reversible neutropenia and gastrointestinal toxicity were the most frequently encountered toxicities. Only two patients developed transient renal failure, and two others developed central nervous system toxicity. No treatment-related death was observed. Of 22 patients who were evaluable for response, 6 (27%) showed an objective response (OR), all ORs being partial responses (PRs) with a median duration of 6 months, and 12 patients had stable disease (SD; 55%) with a median duration of 3.5 months. The median overall survival (OS) was 6 months. Three patients underwent high-dose chemotherapy after showing a response to our IFX schedule. We conclude that continuous-infusion IFX given in an outpatient setting is a feasible and active regimen that produces, a manageable toxicity profile in heavily pretreated breast cancer and sarcoma patients. Early institution of this schedule in less advanced stages could improve the results obtained. Received: 30 June 1996 / Accepted: 20 January 1997     

Phase II study of continuous-infusion high-dose ifosfamide in advanced and/or metastatic pretreated soft tissue sarcomas

Background: Ifosfamide has important activity in pretreated soft tissue sarcomas (STS), and recent data support a clinically significant dose-response relationship for this agent. Administration by continuous infusion and hematopoietic support have rendered dose intensification regimens possible by reducing both hematologic and non-hematologic toxicities. The optimal dose and schedule of ifosfamide when given at high doses remain to be defined. In a previous phase I study, we demonstrated the feasibility of a continuous infusion (c.i.) high-dose ifosfamide (HDI) regimen in the ambulatory setting for patients with advanced solid tumors. The objective of the present phase II study was to assess the antitumor activity and toxicity of such a schedule in patients with advanced pretreated STS.Patients and methods: Thirty-eight patients with advanced and/or metastatic STS, all pretreated with an anthracycline with or without standard-dose ifosfamide, were treated. Ifosfamide was given by c.i. at a dose of 3.5 g/m²/day over four consecutive days, with equidose mesna uroprotection over five days. G-CSF was added at a dose of 200 µg/m²/day subcutaneously from day 6 to day 12. Cycles were repeated every three weeks in the outpatient setting.Results: A total of 159 cycles of therapy were given (median 4 per patient, range 3–6). Treatment compliance was generally satisfactory. The major toxicity was hematologic, with six febrile neutropenic episodes requiring hospitalisation and parenteral antibiotics. Acute renal failure occurred in one patient after three cycles of therapy; central nervous system toxicity was mild. An overall response rate of 39% was observed (95% confidence interval, 26% to 55%), with one complete and 14 partial remissions. All but one of the responder patients had previously received standard-dose ifosfamide. The median response duration was nine months (range 5–21+ months), and the overall median survival ranged from 6–30+ months (median 13 months).Conclusions: High-dose ifosfamide is an active regimen in anthracycline- pretreated STS. Future clinical trials should be aimed at evaluating the impact of different administration schedules on clinical response and outcome. The potential role of HDI as front-line chemotherapy as well as in the adjuvant treatment of STS needs to be investigated in randomized trials.     

Donor Lymphocyte Infusion for the Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

The results of donor lymphocyte infusion (DLI) for treatment of relapse after bone marrow transplantation (BMT) are reviewed. Durable complete remission can be achieved at the molecular level for a majority (more than 70%) of patients with CML, when treated at early relapse. Results are less favourable for acute leukemias, although useful responses have been reported. Data are scarce though promising for myelodysplastic syndromes and multiple myeloma. Major treatment-associated toxicities are GVHD and bone marrow aplasia. The latter complication can be predicted by evaluating the level of residual donor-derived hematopoiesis. Modification of infused cells (CD8 negative selection or transduction with a suicide gene), addition of peripheral blood stem cells, and early implementation of escalating doses may counteract the complications and increase the response rate. Response rate is variably influenced by the presence of chronic GVHD after initial BMT, T-cell depleted BMT, underlying disease and stage at relapse, and the level of mixed chimerism. DLI is a direct demonstration of the graft-versus-leukemia effect (GVL). Because GVL after BMT is sometimes the predominant cause of cure, it may be advisable in such situations to redirect the conditioning regimens for BMT towards engraftment and less immediate cytotoxicity.     

Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with weekly high-dose 48-hour continuous-infusion fluorouracil for advanced colorectal cancer: A Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD) study

Purpose: The objective of this multicenter study was to compare the efficacy and toxicity profiles of a combination of 5-fluorouracil (5-FU) given by bolus injection together with intravenous leucovorin (LV) versus high-dose 5-FU in continuous infusion (CI) in the treatment of advanced colorectal cancer.Patients and methods: A total of 306 patients were randomized to receive either 5-FU 425 mg/m² given by bolus injection on days 1–5 plus intravenous (i.v.) LV 20 mg/m² every four to five weeks or 5-FU 3.5 g/m²/week in a 48-hour CI. Therapy was continued until disease progression. Second-line chemotherapy was allowed in both arms.Results: The response rates in 306 patients with measurable lesions were 19.2% (modulated arm) and 30.3% (CI arm, P < 0.05). The median progression-free survival times were 23.5 weeks (modulated arm) and 25 weeks (CI arm, P = NS). Median survival times were 42.5 weeks (modulated arm) and 48 weeks (CI arm, P = NS). There were no significant differences in grade 3–4 toxicity profiles but if we consider all grades we observed more mucositis in the modulated arm and more hand-foot syndrome in the CI arm.Conclusions: In terms of response rate, the continuous infusion regimen was more effective than the modulated regimen. There was no significant difference in survival and time to progression, and none in grade 3–4 toxicity.     

胃癌术前卡铂腹腔化疗肿瘤组织浓度测定及药代动力学研究

作者采用高效液相色谱法对１０例可切除进展期胃癌进行腹腔卡铂术前化疗药代动力学研究。卡铂３００ｍｇ／ｍ２加生理盐水７５０ｍｌ快速腹腔注射，１６０～１８０ｍｉｎ取腹腔液、门静脉及外周血，２４０～２７０ｍｉｎ取癌组织、癌旁正常组织、腹膜、大网膜、阴性淋巴结，测定总铂浓度。结果表明，腹腔液浓度最高，平均４８．１４μｌ／ｍｌ，门静脉次之为１０．１μｌ／ｍｌ，分别是外周血的８、１．６倍。被测组织中，腹膜浓度超出其它组织浓度（Ρ＜０．０５），癌组织含量高于正常组织。研究证明，卡铂术前腹腔化疗不仅提高腹腔、门静脉药物浓度，而且，在腹膜、癌组织内有一定聚积性，对于杀灭腹腔亚临床病灶，改善临床分期，控制医源性转移，提高治愈性手术切除率发挥重要作用。     

自体癌性胸腹腔积液蛋白质回输临床疗效观察

目的观察浓缩分离的癌性胸腹腔积液蛋白质自体静脉回输的临床疗效.方法采用透析、冷凝、变速离心和抽滤等技术对癌性积液中的蛋白质进行分离提取,将可溶性蛋白稀释在盐水中用于静脉回输.结果该方法提取的蛋白质可浓缩9.78倍,蛋白质浓度可达(262.32±52.36)g/L,其中IL-2、IL-4、IFN 和TNF的浓度(pg/L)分别达到53.34±9.67,47.55±9.25,57.43±15.75和73.50±15.17,提取后浓度明显增加(P<0.05).自体蛋白液回输后无一例发生发热、过敏等副反应,同时水肿也得到一定程度的控制.CD3 、CD8 细胞百分率,总蛋白及IgG浓度均无明显改变(P>0.05),但CD4 细胞百分率和CD4 /CD8 比值明显增加(P<0.05 ).结论通过透析、变速离心及抽滤等技术,可从癌性胸、腹腔积液中浓缩分离出适于静脉输注的蛋白质提取液.自体蛋白质回输以后,水肿得到一定程度的控制,并使CD4 细胞百分率和CD4 /CD8 比值提高.