三维适形加量放疗联合射频热疗治疗局部晚期前列腺癌的临床观察

目的：观察三维适形放射治疗（３ＤＣＲＴ）配合射频热疗治疗局部晚期前列腺癌的近期疗效及耐受性。方法：２３例局部晚期前列腺癌（Ⅲ ～Ⅳ期）患者均行全盆腔放射治疗５０Ｇｙ后进入三维适形放射治疗配合射频热疗。三维适形放射治疗共行２４～２６Ｇｙ。射频热疗使用ＺＲＬ-Ⅰ型热疗仪,射频频率为１３.５６ＭＨｚ,射频电容式透热疗法,每周２次,共行３周。结果：２３例患者全部完成治疗计划。前列腺癌原发病灶完全缓解（ＣＲ）占３４.８％,部分缓解（ＰＲ）占４７.８％,无变化和进展（ＮＣ＋ＰＤ）占１7.４％。总有效率（ＣＲ＋ＰＲ）８２.６％。据ＲＴＯＧ分级急性膀胱炎１～２级１７.４％（４／２３）,急性直肠炎１～２级３９.１％（９／２３）,骨髓抑制发生率１～２级３４.３％（７／２３）,无３级以上不良反应。２３例患者中位随访时间为２８个月。随访率为１００％。结论：三维适形放射治疗配合射频热疗治疗局部晚期前列腺癌的近期疗效好,并发症发生率低。     

三维适形放疗联合多西紫杉醇同期化疗治疗老年局部晚期非小细胞肺癌临床研究

目的：研究三维适形放射治疗联合多西紫杉醇同期化疗治疗老年局部晚期非小细胞肺癌疗效和不良反应。方法：84例局部晚期非小细胞肺癌患者随机分成A组和B组,A组40例采用三维适形放射治疗,总剂量66—70Gy／33—35次,6—7周完成。B组44例采用三维适形放射治疗联合多西紫杉醇同期化疗。结果：两组患者的总有效率分别为57．9％和80．5％,其中CR率分别为7．9％和29．3％,P〈0．05。两组1、2年生存率分别65．7％vs80．5％和39．5％vs53．7％（P〉0．05）。A组患者中位生存期为10．5个月,B组患者为19．5个月。两组患者早期放射反应主要为Ⅰ—Ⅱ级放射性食道炎和骨髓抑制,后期放射反应主要为Ⅰ-Ⅱ级放射性肺炎,发生率两组接近。结论：三维适形放射治疗联合多西紫杉醇同期化疗治疗局部晚期非小细胞肺癌疗效优于单纯三维适形放射治疗。     

食管癌治疗后纵隔淋巴结转移的三维适形放射治疗

目的 探讨食管癌治疗后纵隔淋巴结转移三维适形放疗的价值。方法 44例食管癌患者治疗后2～60个月发生纵隔淋巴结转移，手术后18例，手术加放疗后6例，放疗后20例。单纯适形放疗30例，加用常规放射治疗14例。结果 急性放射性气管炎发生率Ⅰ～Ⅱ级27．3％(12／44)、Ⅲ～Ⅳ级20．5％(9／44)；急性放射性食管炎发生率Ⅰ～Ⅱ级31．8％(14／44)、Ⅲ～Ⅳ级11．4％(5／44)；近期疗效为完全缓解(CR)31．8％(14／44)，部分缓解(PR)50％(22／44)。1、2年生存率分别为72．7％(32／44)、40．9％(18／44)。结论 三维适形放射治疗食管癌治疗后纵隔淋巴结转移有较好的疗效，患者均能耐受。     

三维适形放射治疗常规外照射后复发的食管癌

目的：研究三维适形放射治疗常规放射治疗后复发的食管癌可行性。方法：20例食管癌放射治疗后复发病例，实施适形放射治疗，照射剂量为45～60Gy，3．0Gy／次，1次／d，5d／周。结果：急性放射性食管炎发生率1～2级65％(13／20)、3级35％(7／20)；急性放射性气管炎发生率1～2级35％(7／20)、3级5％(1／20)；骨髓抑制发生率1～2级50％(10／20)、3级0％(0／20)；总有效率为100％，其中完全缓解(CR)80％(16／20)，部分缓解(PR)20％(4／20)。1、2年生存率分别为69．2％(9／13)、42．9％(3／7)。结论：三维适形放射治疗常规外照射后复发的食管癌有较好的近期疗效，早期并发症较低，能为患耐受，晚期并发症的发生率及远期疗效有待进一步观察。     

同期放化治疗局部晚期非小细胞肺癌的临床研究

目的：观察同期放、化疗加适形(3D-CRT)补量放疗治疗局部晚期非小细胞肺癌的近期疗效和毒副反应。方法：36例局部晚期非小细胞肺癌(Ⅲa或Ⅲb期)患进入同期放化疗加适形补量组，全部患均行TP方案(紫杉醇140～160mg／m^2 d1给予；顺铂60～80mg／m^2 d1或分2～3d给予；21d为1个周期)化疗加常规放射治疗结合3DCRT补量同步治疗。结果：36例全部完成治疗计划，肺原发灶完全缓解（CR)占19．4%，部分缓解(PR)占75．0％，无变化和进展(NC PD)占5．6％，总有效率(CR PR)为94．4％；1～2级急性骨髓抑制发生率为89％，3～4级为36％。1～2级放射性食管炎和放射性肺炎的发生率分别为44％和11％，无3～4级发生率。12、18月生存率分别为78．9％、63．2％，12、18月局部控制率为68．4%、47．4％。结论：同期放化疗加适形补量治疗局部晚期非小细胞肺癌能为绝大多数患耐受，有较好的近期疗效。     

三维适形放射治疗高龄肺癌30例临床分析

目的 探讨三维适形放射治疗(three-dimensional conformal radiotherapy，3D-CRT)治疗Ⅰ～Ⅲ期高龄非小细胞肺癌的疗效及副作用。方法 对30例行3D-CRT治疗的Ⅰ～Ⅲ期高龄非小细胞肺癌进行回顾性分析。30例患者共设46个靶区。靶区剂量归一到等中心处，分割剂量3～5Gy，总量42～66Gy，3～5次／周，周剂量≤15Gy。结果 总1、2、3年生存率及中位生存期分别为65．8％、41、2％、20、6％、23个月。肿瘤1、2、3年局部控制率分别59．8％、31．1％、28．3％。放射性肺炎发生率为16．7％(5／30)，其中≥3级放射性肺炎发生率为6．7％(2／30)，1例因放射性肺炎而死亡。放射性肺纤维化发生率为10、0％(3／30)，均为1～2级。放射性食管炎的发生率分别为43．3％(13／30)．均为1～2级。结论 利用3D-CRT治疗提高肿瘤剂量，从而提高高龄肺癌的生存率，并发症低，是治疗高龄肺癌的较好手段。     

适形放疗与常规放疗结合治疗Ⅲ期肺鳞癌疗效分析

自1996年10月—2000年10月对118例Ⅲ期肺鳞癌常规放射治疗40—50Gy(平均44．6Gy)后的残留病灶再行适形放疗。肿瘤边缘单次处方剂量平均为6．8Gy，间隔1—2d，总照射剂量平均为39．4Gy。肿瘤靶体积(GTV)0．8cm^3-148．6cm^3，平均36．6cm^3，计划靶体积(PTV)3．6cm^3—213．5cm^3，平均51．4cm^3。近期肿瘤退缩率分别为CR30．5％(36／118)、PR53．4％(63／118)、NR11．9％(14／118)和PD4．2％(5／118)，总有效率(CR PR)83．9％。1、2、3年生存率分别为68．6％(81／118)、35．6％(31／87)和12．2％(6／49)，局部控制率分别为92．4％(109／118)、85．1％(74／87)和79．6％(39／49)。急性放射性肺炎Ⅰ—Ⅱ级27．1％(32／118)，Ⅲ级3．4％(4／118)，Ⅳ级0(0／118)。急性放射性食管炎Ⅰ—Ⅱ级16．1％(19／118)，Ⅲ—Ⅳ级0(0/118)。骨髓抑制Ⅰ—Ⅱ级9．3％(11／118)，Ⅲ—Ⅳ级0(0／118)。晚期放射性食管反应Ⅲ级1例，放射性肺损伤Ⅱ级1例。结果说明，对Ⅲ期肺鳞癌常规放疗后再行适形放疗局部加量照射，患者可耐受，疗程短，提高肿瘤控制率，延长生存期，是局部剂量升级的有效方法。     

调强适形放疗联合化疗及射频热疗对局部晚期非小细胞肺癌的疗效研究

目的研究调强适形放疗联合化疗及射频热疗,治疗局部晚期非小细胞肺癌的疗效及不良反应。方法将84例NSCLC患者随机分成两组（治疗组与对照组）,每组42例。治疗组采用调强适形放疗,常规分割2 Gy/次,每周5次,总剂量60 Gy/30次;化疗采用NP方案,与放疗同步进行,并同时行射频热疗,每周2次。对照组单纯采用NP方案化疗。结果治疗组放射性肺炎发生率为2.4%,放射性食管炎发生率为26.2%,Ⅰ～Ⅱ度白细胞下降发生率为47.6%,Ⅲ度白细胞下降发生率为14.3%,中位生存期为17.6个月,1、2、3年生存率分别为63.5%、38.5%、29.5%,而对照组Ⅰ～Ⅱ度、Ⅲ度白细胞下降发生率分别为42.9%、11.9%,中位生存期为11.3个月,1、2、3年生存率分别为41.0%1、2.4%4、.0%。结论调强适形放疗联合同期化疗及射频热疗治疗局部晚期非小细胞肺癌,可明显提高患者局部控制率及1、2、3生存率,且不良反应小。     

三维适形放射治疗配合化疗治疗局部晚期非小细胞肺癌

目的：观察三维适形放射治疗（3DCRT）配合化疗治疗局部晚期非小细胞肺癌的耐受性及近期疗效。方法：24例局部晚期非小细胞肺癌（Ⅲa或Ⅲb期）患者进入三维适形放射治疗加化疗组，全部患者均行NP方案（N：去甲长春花碱25mg/m^2第1、8天给予；P：顺铂60－80mg/m^2第1天或分2－3d给予；21d为1个周期）化疗加3DCRT同步治疗。结果：24例全部完成治疗计划，肺原发灶完全缓解（CR）占16．7％，部分缓解（PR）占75．0％，无变化和进展（NR＋PD）占8．3％，总有效（CR＋PR）率为91．7％，纵隔转移淋巴结完全缓解（CR）占36．4％，部分缓解（PR）占63．6％，无变化和进展（NR＋PD）占0％，总有效（CR＋PR）率为100％。白细胞下降发生率为95．8％，其中3、4级白细胞下降为54．2％；放射性食管炎和放射性肺炎的发生率分别为54．2％和12．5％，均有1、2级。结论：三维适形放射治疗配合化疗治疗局部晚期非小细胞癌能为绝大多数患者耐受，有较好的近期疗效。     

适形放射治疗Ⅱ-Ⅲ期非小细胞肺癌初步报道

目的：研究三维适形放射治疗非小细胞肺癌(NSCLC)的疗效、副反应及患者的耐受性。方法：2000年10月～2001年7月，25例不能手术的Ⅱ-Ⅲ期非小细胞肺癌采用常规全纵隔或半纵隔 患侧肺门 原发病灶前后两野对穿外照射，照射肿瘤的剂量达8MV-X DT40～41．4Gy／20～23次／4～4．4周后，由CMS公司FOCUS2．6．1三维治疗计划系统设计、DVHs评价和优化适形治疗计划。计划靶区为临床靶区外放1．0～1．5cm，计划适形照射总剂量为25～30Gy，2．5～3Gy／次，1次／天，5天／周，肺作不均质密度校正，照射方法均为非共面野。按RTOG和WHO标准观察急性放射反应及近期疗效，评价患者的耐受性。结果：25例患者均顺利完成治疗，肿瘤中位剂量70．12Gy(62．45Gy～71．40Gy)。近期疗效为CR16．0％(4／25)，PR56．0％(14／25)，NC20．0％(5／25)，PD8．0％(2／25)，总有效率为72．0％(18／25)。根据RTOG分级，急性放射性食管炎1～2级24．0％(6／25)，3级4．0％(1／25)；急性放射性肺炎1～2级16．0％(4／25)，3级4．0％(1／25)；骨髓抑制1～2级16．0％(4／25)；心脏损伤1～2级12．0％(3／25)；随访至2002年7月，死亡7例，一年生存率75．15％。25例患者的中位随访期为14个月(6～18个月)，随访率为96％。结论：由于提高了分割量及总剂量，三维适形放射治疗不能手术的非小细胞肺癌可取得较好的近期疗效，并且经剂量-体积直方图(DVHs)优化治疗计划，减少了正常组织的照射剂量，使治疗能为患者耐受。由于样本较小，病例仍在进一步累积中，晚期并发症的发生率及远期疗效有待进一步观察。     

Toxicology and pharmacokinetics of (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38)

Preclinical studies on toxicology and pharmacokinetics were performed for (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38) in rats and a dog after ld₁₀ and ld₅₀ assessment in mice. In drug-treated rats, ura and creatinine concentrations were 1,4-1.9 times those in control rats. Histopathology showed necrosis of tubular epithelium of the kidneys, which was comparable to damage observed after treatment with cisplatin (CDDP), and extensive necrosis of crypt epithelium, especially in the ileum.Similar to CDDP, TNO-38 was emetic in the dog. Non-specific subacute inflammatory changes were observed in the ileum. Renal damage was much less pronounced.Half-lives of distribution and elimination were 6.2 min and 5.2 days, respectively. The cumulative excretion of Pt in urine over 1 and 7 days after drug treatment was 38.3 and 49.3% of the dose, respectively. Twelve weeks after drug administration, Pt concentrations were highest in kidneys and liver.TNO-38 is adequately water soluble. Its reported antitumour activity is consistently lower than that of CDDP. The drug's toxicity was, in general, comparable to that of CDDP. Its pharmacokinetic profile was very similar to that of CDDP. It is concluded that TNO-38 should probably not be further evaluated in clinical studies.     

Antitumor effects of three platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-platinum (II) monohydrate (DWA2114R), cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP), in mice.

(-)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R), cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP) were compared for their antitumor effects and nephrotoxicity-inducing activities at the same dosage (1/8, 1/4, 1/3, 1/2, 2/3 or 3/4 of the LD10 or LD10) on the basis of their intravenous lethal doses in mice. DWA2114R was effective against murine tumor lines, Colon 26 and Colon 38 carcinomas, M5076 ovarian sarcoma and P388 L1210 leukemias, implanted subcutaneously (s.c.). Triple injection every other day of DWA2114R was more effective than a single injection at each sublethal dose. The antitumor effects of DWA2114R against these tumors were more effective than or were similar to those of CBDCA and CDDP. The antitumor effect against CDDP-resistant L1210 leukemia implanted s.c. was only observed in the treatment of DWA2114R, but not in CBDCA and CDDP. No excellent antitumor effects of three platinum complexes were observed against Lewis lung carcinoma and B16 melanoma implanted s.c. even at triple injection every other day, and no effect was obtained against Meth-A fibrosarcoma under similar conditions. While the treatment of CDDP showed marked increases in levels of blood urea nitrogen and of urinary protein and sugar at effective doses in the antitumor evaluations, the treatment of DWA2114R as well as CBDCA showed no increase in these parameters. These results indicate that DWA2114R represents a desirable second generation antitumor platinum complex.     

Clinical trials of Herceptin(R) (trastuzumab)

This report summarises the clinical efficacy and safety findings from clinical trials of the new anti-HER2 monoclonal antibody Herceptin(R) (trastuzumab). Data from pivotal trials indicate that trastuzumab is active when added to chemotherapy in patients with advanced metastatic breast cancer. In particular, the combination significantly prolonged the median time to disease progression, increased the overall response rate, increased the duration of response, and improved median survival time by approximately 25% compared with chemotherapy alone. Furthermore, trastuzumab is active as a single agent in women with HER2-positive metastatic breast cancer, inducing durable objective tumour responses. In total, 15% of patients who had received extensive prior treatment for metastatic disease had an objective response. The median duration of response was 9.1 months following administration of single-agent trastuzumab. Notably, 2% of patients were free of disease progression at 6 months. The safety profile of trastuzumab either given alone or in combination was favourable.     

In vitro evaluation of dichloro-bis(pyrazole)palladium(II) and dichloro-bis(pyrazole)platinum(II) complexes as anticancer agents

Introduction  Cisplatin (cis-diamminedichloroplatinum) was first identified for its anti-bacterial activity, and was later also shown to be an efficient anticancer agent. However, the therapeutic use of this anticancer drug is somewhat limited by its toxic side effects, which include nephrotoxicity, nausea, and vomiting. Furthermore the development of drug-resistant tumours is commonly observed following therapy with cisplatin. Hence there is a need for improved platinum derived drugs to overcome these limitations. Aims  Apoptosis contributes significantly to the cytotoxic effects of anticancer agents such as cisplatin; therefore in this study the potential anticancer properties of a series of pyrazole palladium(II) and platinum(II) complexes, [(3,5-R₂pz)₂PdCl₂] {R = H (1), R = Me (2)} and [(3,5-R₂pz)₂PtCl₂] {R = H (3), R = Me (4)}, were evaluated by assessment of their pro-apoptotic activity. Methods  The induction of apoptosis was measured in CHO cells by the detection of phosphatidylserine (PS) exposure using the annexin V and APOPercentage™ assays; DNA fragmentation using the Terminal deoxynucleotide transferase dUTP Nick End Labelling (TUNEL) assay; and the detection of activated caspase-3. Results  The platinum complexes were shown to be considerably more active than the palladium complexes, with complex 3 demonstrating the highest level of cytotoxic and pro-apoptotic activity. The LD₅₀ values for complex 3 and cisplatin were 20 and 70 μM, respectively, demonstrating that the cytotoxic activity for complex 3 was three times higher than for cisplatin. Various human cancer cell lines, including CaSki, HeLa, as well as the p53 mutant Jurkat T cell line were also shown to be susceptible to complex 3. Conclusions  Collectively, this in vitro study provides insights into action of palladium and platinum complexes and demonstrates the potential use of these compounds, and in particular complex 3, in the development of new anticancer agents.     

Synergism of cytotoxicity between cis-diaminedichloro-platinum-(ii) and cis-diamine(1,1-cyclobutanedicarboxylate)-platinum-(ii)

In an attempts to increase the antitumor effect and to reduce normal tissue toxicity, the combined cytotoxic effect of cis-Diamminedichloroplatinum (II) (CDDP) and cis-diammine(1,1-cyclobutane dicarboxylate) platinum (II) (CBDCA) was investigated using HeLa and colon 26 cell lines and the combination index (CI). Cytotoxicity of the combination of CDDP and CBDCA on 27 surgically resected specimens of human gastric and colorectal adenocarcinomas was also evaluated using the in vitro succinate dehydrogenase inhibition (SDI) test. The CI values varied with the dose ratio examined (1:1-1:6) of CDDP and CBDCA, with findings that CI<1, synergy, was obtained at fraction affected (Fa)>0.75 for HeLa cells and at Fa<0.9 for colon 26 cells in cases of a dose ratio of 1:1 to 1:2. Of all 27 clinical human adenocarcinomas, the succinate dehydrogenase (SD) activity was significantly lower in cancer cells concomitantly exposed to both CDDP and CBDCA than in those exposed to either drug alone. These positive effects of a combination of two platinum analogues on human malignant tissues have heretofore not been reported, which would warrant the clinical application of this combination for human malignant tumors.