LFP和FP方案治疗晚期食管癌的研究

目的 探讨晚期食管癌应用ＬＦＰ方案治疗的疗效与毒副作用,方法 １９９４年１月至９１９７年１２月我院内科用ＬＦＰ方案（低剂量ＣＦ＋５－Ｆｕ＋ＰＤＤ）与ＦＰ方案（５－Ｆｕ＋ＰＤＤ）非随机对照治疗晚期食管癌５８例,全部病例经病理学或细胞学确诊,并有可测量的临床及Ｘ线观察指标,２组临床情况基本相同,具可比性。结果 ＬＦＰ方案治疗３０例,ＣＲ１例（３．３％）ＰＲ１６例（５３．３％）有效率（ＣＲ＋ＰＲ）５６．     

口服大剂量CF加PF方案与PF方案联合放射治疗晚期鼻咽癌疗效比较

目的：对比观察口服大剂量醛氢叶酸,５－ＦＵ,ＤＤＰ（ＰＦＬ）与ＰＦ方案联合治疗晚期及复发转移的鼻咽癌的疗效。方法 １９９６～１９９８年间,１００例局部晚期及复发转移的鼻咽癌,非随机分为ＣＦ组（ＰＦＬ方案）５１例,对照组（ＰＦ方案）４９例。晚期初治采用放化疗综合治疗（Ｃ＋Ｒ）复发转移采用单纯化疗（Ｃ）。结果 ＣＦ组初治２８例,其ＣＲ率,有效率分别为６４．２％,８５．７％,中位生存期２１月（４－３３月     

DDP,5Fu／CF加干扰素治疗晚期鼻咽癌的初步报告

目的：评价ＤＤＰ＋５Ｆｕ／ＣＦ＋ＩＮ（干扰素）方案治疗晚期鼻咽癌的疗效和毒性反应。方法：本文采用ＤＤＰ＋５Ｆｕ／ＣＦ＝ＩＮＦ（ＤＤＰ２０ｍｇ／ｍ＾２×５，５Ｆｕ３００ｍｇ－４００ｍｇ／ｍ＾２×５，ＩＮＦ３×１０＾６Ｕ×３）方案共治疗晚期鼻咽癌２６例；结果：２５例可评价儿，总有效率（ＣＲ＋ＰＲ）８０％（２０／２５），ＣＲ率１２％，中位缓解期４．８月（２－１２月）。在放疗和／七化疗后复发转移的２１例中     

顺铂或卡铂加氟脲嘧啶对中晚期鼻咽癌诱导化疗的疗效对比

为比较两种铂类药物单疗程治疗鼻咽癌的临床疗效及毒副作用，作者于１９９６年３月～１０月，将３４例有颈淋巴结转移的中晚期鼻咽癌患者分为两组（每组各１７例）分别采用ＣＢＰ３００ｍｇ／ｍ２，第１天，５－Ｆｕ１０００ｍｇ／ｍ２，第１～５天或ＤＤＰ１００ｍｇ／ｍ２，第１天５－Ｆｕ１０００ｍｇ／ｍ２，第１～５天两种化疗方案进行放疗前单疗程诱导化疗。ＣＢＰ组ＣＲ＋ＰＲ（ＯＲ）为５２．９４％，ＤＤＰ组为６４．７１％，Ｐ＞０．０５，无显著性差异。两组ＷＢＣ值多在第３周最低，第４周回升。ＣＢＰ＋５－Ｆｕ组ＷＢＣ均值从第１周起均较ＤＤＰ＋５－Ｆｕ组低，按ＷＨＯ毒性与分级标准，两组ＷＢＣ值下降分级比较，３＋４度者，ＣＢＰ＋５－Ｆｕ组４７．０６％（８／１７），ＤＤＰ＋５－Ｆｕ组１１．７６％（２／１７），Ｐ＜０．０５，有显著性差异。本组资料提示ＣＢＰ与ＤＤＰ对中晚期ＮＰＣ诱导化疗疗效相近，ＣＢＰ不需水化，可在门诊执行，两组对ＷＢＣ的抑制均在第３周最重，且ＣＢＰ对ＷＢＣ影响要较ＤＤＰ严重     

ELFP治疗24例晚期上消化道癌的近期疗效分析

本文总结我院１９９４年２月至１９９６年１月，将醛氢叶酸（ＣＦ）合并５－氟脲嘧啶（５－Ｆｕ）足叶乙甙（ＶＰ－１６）及顺铂（ＰＤＤ），构成ＥＬＦＰ联合化疗方案治疗晚期食道癌和胃癌２４例，总有效率６２．５％（１５／２４），其中ＣＲ８．３％（１／２４），ＰＲ５４．２％（１３／２４）毒副作用主要为胃肠道反应，胃髓抑制，脱发。     

大剂量醛氢叶酸加5-Fu、卡铂治疗晚期鼻咽癌近期疗效观察

２０例晚期鼻咽癌患者经用ＨＤＣＦ／５－Ｆｕ＋卡铂联合化疗，可评价１９例，取得ＣＲ１例、ＰＲ１２例、ＭＲ５例、ＰＤ１例，有效率（ＣＲ＋ＰＲ）６８．４％。毒性反应主要有；白细胞降低、口腔粘膜炎等，但多数见于Ⅰ－Ⅱ级，绝大多数病人可以耐受。ＨＤＣＦ／５Ｆｕ＋铂联合化疗是目前治疗晚期鼻咽癌的有效方案之一。     

HDCF/5-Fu、DDP联合方案治疗晚期鼻咽癌的近期疗效分析

为了提高５－Ｆｕ＋ＤＤＰ方案治疗复发、转移性鼻咽癌的临床疗效，对２８例晚期ＮＰＣ患者给予２个以上疗程的ＨＤＣＦ／５－Ｆｕ＋ＤＤＰ方案化疗，结果ＣＲ２例、ＰＲ１１例、ＭＲ６例、ＳＤ４例、ＰＤ５例，总有效率为（ＣＲ＋ＰＲ）４６．４％，中位缓解期５．４个月（２～１６个月）。毒性反应主要有ＷＢＣ下降、恶心呕吐、口腔粘膜溃烂等。ＨＤＣＦ／５－Ｆｕ＋ＤＤＰ方案较传统的单用５－Ｆｕ＋ＤＤＰ方案疗效有明显提高，但毒性反应亦较重     

大剂量醛氢叶酸（HDCF）、5－Fu、DDP联合治疗晚期鼻咽癌的初步报告

我们以ＨＤＣＦ／５－Ｆｕ＋ＤＤＰ（或Ｃａｒｂｏｐｌａｔｉｎ）方案治疗转移、复发或晚期鼻咽癌２７例。２３例可评价客观疗效，取得ＣＲ２例，ＰＲ１４例，ＳＤ６例和ＰＤ１例，总有效率（ＣＲ＋ＰＲ）６９．６％。中位缓解期４月（１－１１月），目前仍有７例在缓解中。１１例因鼻咽癌骨转移引起的骨痛，化疗后疼痛缓解率达１００％，毒性反应以白细胞下降，口腔炎、恶心、呕吐和皮肤色素沉着为主。绝大多数病人均可耐受，未见肝、肾功能损害及因毒性致死的病例。作者认为，ＨＤＣＦ／５－Ｆｕ＋ＤＤＰ联合方案是目前治疗鼻咽癌的新的较有效的化疗方案，部分病例对ＤＤＰ（Ｃａｒｂｏｐｌａｔｉｎ）＋５－Ｆｕ抗药时，本方案仍可奏效。如果严格控制５－Ｆｕ的剂量在３５０－５００ｍｇ／ｍ２／天，其毒性是可逆的，值得继续探索其实际的临床价值。     

PF方案化放治疗晚期鼻咽癌的远期疗效

目的探索用ＰＤＤ／５－Ｆｕ方案化放治疗晚期鼻咽癌的疗效。方法１９８９年１２月～１９９０年１２月间,选择７６例Ⅲ、Ⅳ期鼻咽癌患者,先作３周期ＰＤＤ（２０ｍｇ（ｍ２）－１ｄ－１,ｉｖ,第１～５天）和５－Ｆｕ［７００ｍｇ（ｍ２）－１ｄ－１,连续静脉滴注,第１～５天］诱导化疗,随后尽快作放疗,此为综合治疗组。以１９８９年作单纯放疗的８６例晚期鼻咽癌患者作对照组。两组放疗方法、时间／剂量分割均相同。结果化疗有效率为８９．３％,完全缓解率为１８．４％。综合治疗组（综合组）总的５年生存率为４８．７％,对照组为３３．７％（Ｐ＞０．０５）。综合组Ｔ２Ｎ３和Ｔ２～４Ｎ３患者的５年生存率为４４．１％和３９．５％,均明显高于对照组的２１．６％及２０．４％（Ｐ＜０．０５）。结论ＰＦ方案化放治疗提高了Ｔ２～４Ｎ３患者的５年生存率。     

低剂量醛氢叶酸,5—氟尿嘧啶和顺铂治疗晚期食管癌50例临床观察

我们从１９９４年１０月－１９９８年１０月采用由低剂量醛氢叶酸（ＣＦ）、５－氟尿嘧啶（５－Ｆｕ）和顺铂（ＰＤＤ）组成的ＬＦＰ方案治疗晚期食管癌５０例,与同期用５－Ｆｕ和ＰＤＤ组成的ＦＰ方案治疗晚期食管癌４８例对照,比较两组的近期疗效与毒副反应。结果显示...     

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.