Phase I/II trial of dipyridamole, 5-fluorouracil,leukovorin, and mitoxantrone in metastatic breast cancer

Summary Based upon the hypothesis that dipyridamole would potentiate the cytotoxicity of mitoxantrone and the combination of 5-fluorouracil (5-FU) and leukovorin, we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m² by mouth every 6 h (700 mg/m²/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m² was given intravenously immediately prior to 5-FU 375 mg/ m² intravenously on days 1–5. Mitoxantrone 6 mg/m² was given as a single dose on day 3. Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m² days 1–2, 5-FU 375 mg/m² days 1–2, mitoxantrone 6 mg/m² on day 2, and dipyridamole 175 mg/m² every 6 h on days 0–3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.     

药物敏感试验指导肺癌合并恶性胸腔积液的顺铂联合其他药物胸腔内化疗

目的用药物敏感试验预测肺癌合并恶性胸腔积液癌细胞对顺铂联合其他药物的敏感度，观察其在指导此类患者的顺铂联合其他化疗药物胸腔内化疗的价值。方法将44例胸腔积液癌细胞阳性肺癌患者随机分为两组：药物敏感试验组（20例，有2例因体外药物敏感试验失败而被排除）和对照组（22例）。药物敏感试验组患者用三磷酸腺苷-肿瘤细胞药物敏感试验（ATP-TCA）法分别检测胸腔积液癌细胞对顺铂加香菇多糖、顺铂加甘露聚糖肽、顺铂加A群链球菌制剂、顺铂加干扰素、顺铂加金黄色葡萄球菌滤液制剂、顺铂加卡介苗多糖核酸、顺铂加红色诺卡菌细胞壁骨架、顺铂加白细胞介素-2的敏感度，并选择抑瘤率最高的联合化疗药物对患者进行胸腔内化疗，观察治疗后胸腔积液完全缓解率及胸腔积液癌细胞转阴率，并与对照组比较。结果药物敏感试验组患者对各联合化疗药物敏感的例数为：顺铂加香菇多糖14例、顺铂加甘露聚糖肽18例、顺铂加A群链球菌制剂17例、顺铂加干扰素10例、顺铂加金黄色葡萄球菌滤液制剂16例、顺铂加卡介苗多糖核酸15例、顺铂加红色诺卡菌细胞壁骨架17例、顺铂加白细胞介素-216例。药物敏感试验组完全缓解率为65．0％，对照组为27．3％（P〈0．05）。药物敏感试验组胸腔积液癌细胞转阴率为80．0％，对照组为45．5％（P〈0．05）。结论用药物敏感试验指导肺癌合并恶性胸腔积液的胸腔内个体化化疗可提高完全缓解率和胸腔积液癌细胞转阴率，该方法具有临床实用价值。     

两种化疗方案治疗晚期非小细胞肺癌的对比观察

目的比较化疗方案GP(吉西他滨和顺铂)和IVP(异环磷酰胺、长春地辛和顺铂)治疗晚期非小细胞肺癌(NSCLC)的疗效和毒性.方法将62例晚期NSCLC患者随机分成两组,治疗组30例,采用GP方案:吉西他滨1000 mg/m^2第1、第8 d静脉滴注,顺铂80 mg/m^2第1 d静脉滴注,4周为一周期;对照组32例,采用IVP方案:异环磷酰胺1200 mg/m^2第1～第3 d静脉滴注,长春地辛2.5 mg/m^2第1、第8 d静脉推注,顺铂80 mg/m^2第1 d静脉滴注,4周为一周期.2个周期后评价其疗效及毒性.结果治疗组无一例完全缓解,部分缓解6例,总有效率20.0%;对照组亦无一例完全缓解,部分缓解8例,总有效率25.0%.两组无统计学差异(P＞0.05),但治疗组毒性小于对照组.结论双药化疗方案GP治疗NSCLC的疗效不低于三药方案IVP,且毒副作用轻微,更易为晚期肺癌患者所接受.     

局部性尤文肉瘤综合治疗临床分析

目的　探讨局部性尤文肉瘤的综合治疗效果。方法　收集经综合治疗的 2 5例尤文肉瘤患者的临床资料 ,采用Kaplan Meier法进行分析、Logrank法检验 ,分析治疗方式和化疗周期对疗效的影响。结果　综合治疗局部性尤文肉瘤的有效率为 92 % (2 3 /2 5 )。治疗结束后病灶完全消退组患者的 1、3、5年生存率 (10 0 %、93 .8%和 81.3 % )明显高于病灶未完全消退组 (10 0 %、75 .0 %和 5 0 .0 % ) (均P <0 .0 5 )。行 6个周期化疗的患者 1、3、5年生存率 (10 0 %、93 .8%和 66.7% )高于 3个周期者 (88.9%、77.8%和 5 5 .6% ) (均P <0 .0 1)。局部采用手术或放疗对疗效无明显影响 (P >0 .0 5 )。结论　经综合治疗 ,局部性尤文肉瘤病灶完全消退者生存期明显延长 ,化疗周期的次数是影响疗效的重要因素。     

放疗化疗联合治疗局部晚期非小细胞肺癌43例

目的 探讨以顺铂为主的化疗方案加放疗对局部晚期非小细胞肺癌的疗效。方法 86例局部晚期非小细胞肺癌患随机分为治疗组及对照组各43例，放疗方案以CAP、EP、MVP或MOP，每人至少化疗两个周期，化疗后10～14天放射治疗，放疗采用^60Co外照射。结果 治疗组有效率83．7％，中位生存期14．5个月，对照组有效率67．4％，中位生存期10个月，两组不良反应为骨髓抑制、胃肠道反应。结论 以顺铂为主的化疗方案加放疗治疗局部晚期非小细胞肺癌的疗效较高，可提高肿瘤的局部控制率和延长生存期。     

腹壁下动脉插管化疗在子宫颈及阴道恶性肿瘤的应用

我科6年中对子宫颈及阴道恶性肿瘤施行腹壁下动脉插管化疗共34例,作为配合放疗及争取手术的综合疗法之一,提高晚期宫颈癌的放疗效果,对Ⅱ期早宫颈癌施行根治术者6例,但对腺癌、肉瘤及恶性黑色素瘤等效果差。     

多希紫杉醇联合顺铂治疗晚期非小细胞肺癌疗效观察

目的观察和评价多希紫杉醇联合顺铂(DP方案)治疗晚期非小细胞肺癌的疗效和毒性。方法将我科近几年收治的48例晚期非小细胞肺癌患者随机分为治疗组和对照组。治疗组采用多希紫杉醇联合顺铂(DP方案),对照组采用长春瑞滨联合顺铂(NP方案)。2周期化疗后进行疗效、毒性对比研究。结果治疗组和对照组近期有效率分别为45.5%和37.5%,疾病进展时间(TTP)分别为6.3和5.9个月,中位生存期分别为10.1和9.0个月,1年生存率分别为45.8%和39.4%,两组间比较差异均无显著性(P>0.05)。治疗组在恶心呕吐、骨髓抑制等毒性反应发生率方面低于对照组,差异有显著性(P<0.05)。结论多希紫杉醇联合顺铂治疗晚期非小细胞肺癌与NP方案相比较,疗效相似,但毒性反应低于NP组,患者更易耐受,可广泛应用于临床。     

潘生丁增强氨甲蝶呤的抗肿瘤作用

外源性核苷能抵消抗代谢药对肿瘤细胞的杀伤作用;核苷转运抑制剂潘生丁则能阻断核苷的这种抵消作用,从而增强抗代谢药的细胞毒性。本研究证明,胸苷和次黄嘌呤可明显抵消氨甲蝶呤对L1210细胞的杀伤作用,潘生丁则能有效地阻断核苷的抵消作用;潘生丁和两性霉素B合用可明显增强氨甲蝶呤对小鼠S180肉瘤的抑制作用,但不增强氨甲蝶呤对动物的毒性。提示潘生丁有可能应用于肿瘤联合化疗。     

Immediate versus delayed chemotherapy in patients with asymptomatic incurable metastatic cancer

Aim: To examine the evidence of benefit in initiating immediate chemotherapy in patients with newly diagnosed asymptomatic metastatic incurable cancer, compared with delaying chemotherapy until symptomatic progression. Methods: Through an extensive review of published reports, we examined the biological, clinical, psychological and ethical background of the issue and reported on the available clinical trial evidence in a variety of tumor types. Results: Only a limited number of clinical trials have directly examined the role of immediate versus delayed chemotherapy in patients with incurable asymptomatic metastatic cancer. Small studies in mesothelioma, colorectal cancer, breast cancer, myeloma, and low‐grade lymphoma suggest no survival benefit for the immediate initiation of chemotherapy. However, there was no evidence in other tumor types. Conclusion: The appropriate timing of chemotherapy initiation in an asymptomatic patient with metastatic cancer remains a substantial question in oncology. Many factors are likely to impact on the decision. However, little if any evidence demonstrates a clear advantage in the immediate initiation of chemotherapy in this setting.