顺铂和替加氟联合放疗治疗中晚期食管癌疗效观察

目的观察顺铂和替加氟联合放疗治疗食管癌的临床疗效及其毒副反应。方法2003年1月至2006年2月对60例食管癌患者采取顺铂20mg·m-2·d,替加氟750mg·m-2·d,连用5天,序贯放疗60~70Gy/6~7周。结果60例患者中,CR24例,PR18例,SD9例,PD9例,RR(CR+PR)为70·0%,主要毒副作用为骨髓抑制、恶心呕吐。肝肾功损害及口腔炎、静脉炎等较轻。结论顺铂和替加氟联合放疗治疗食管癌疗效好,耐受性好值得推广应用。     

紫杉醇联合草酸铂、卡培他滨三药方案治疗晚期转移性鼻咽癌的临床研究

目的探讨紫杉醇联合草酸铂、卡培他滨三药方案治疗晚期转移性鼻咽癌的疗效及不良反应。方法2002年1月至2005年1月，110例晚期转移性鼻咽癌病人入组：试验组55例患者．第1天应用紫杉醇135mg／m^2、草酸铂130mg／m。静脉滴注，口服卡培他滨1650mg／m^2／d，连服l-14d，每3周为一个周期，连用2-4个周期；对照组55例患者，第1-5天应用DDP 20mg／m^2、5-Fu 0．5g／m^2静脉注射，3周为一个周期，连用2-4个周期；治疗结束2-4周后评价疗效。结果试验组疗效可评价55例，对照组疗效可评价53例。试验组与对照组有效率分别为（CR＋PR）50．9％（28例）和32．1％（17例），两者差异有统计学意义（P〈0．05）。试验组和对照组中位生存时间为10．6个月和8．6个月，两者差异有统计学意义（t〈0．05）。安全性方面：试验组Ⅳ反应主要为手足综合征8例（14．5％）、骨髓抑制2例（3．6％）和消化道毒性4例（7.3％）；对照组Ⅳ反应主要为消化道毒性8例（15.1％）、骨髓抑制2例（3.8％）。结论紫杉醇联合草酸铂、卡培他滨三药方案对晚期转移性鼻咽癌的疗效较DDP＋5-Fu有优势，且不良反应可以耐受。     

Increased aneuploidy in spermatozoa from testicular tumour patients after chemotherapy with cisplatin, etoposide and bleomycin

Testicular cancer is the most common neoplasia occurring in the young male population. The PEB (cisplatin, etoposide and bleomycin) adjuvant chemotherapy usually proposed after orchidectomy in non seminomatous tumours, and in metastatic seminomas, has improved the long-term survival of these patients. Following an azoospermic period, sperm cell recovery is generally observed after treatment delivery, but little is known about the genetic consequences on these new spermatozoa. To estimate the chromosomal consequences of this chemotherapy on sperm cells during the period of recovery of spermatogenesis, sperm cell aneuploidy was studied in testicular cancer patients, at 6-18 months after PEB adjuvant chemotherapy delivery, using fluorescence in-situ hybridization (FISH) of chromosomes 7, 16, 18, X and Y with specific DNA probes. A significant increase in the frequency of diploidy and disomy for chromosomes 16, 18 and XY was observed in treated patients compared with a healthy control group. Spermatozoa aneuploidy occurring during the spermatogenesis recovery period might be a possible side effect of the PEB regimen. Thus, practitioners should be advised to provide counselling about the need for an appropriate duration of contraception. Moreover, genetic counselling should be offered in cases of pregnancy occurring soon after the end of chemotherapy.     

After chemotherapy,functional humoral response capacity is restored before complete restoration of lymphoid compartments

Chemotherapy has, besides the beneficial effects, several adverse effects. Suppression of the immune system is one of the most important problems. Infections caused by encapsulated bacteria like Streptococcus pneumoniae are responsible for a major part of infectious problems during and after treatment. The splenic marginal zone is essential in the initiation of an immune response to encapsulated bacteria. In this study, we analysed the effects of three different cytostatic agents on humoral immune responses. We found a reduced, but detectable immune response capacity at two days after treatment although the marginal zone B cell population is severely reduced at this time point. Twenty-four days after cessation of treatment, the immune response capacity was largely restored although lymphoid compartments were still not completely restored at that time point. Apparently, the presence of only few marginal zone B cells is sufficient to evoke a rise in antibody titres and although antibody titre increases are low, even small rises are most likely clinically relevant.     

Fluoropyrimidine chemotherapy in a rat model: comparison of fluorouracil metabolite profiles determined by high-field 19F-NMR spectroscopy of tissues ex vivo with therapy response and toxicity for locoregional vs systemic infusion protocols

A Sprague-Dawley rat model with DS sarcoma transplanted in the thigh was used to compare transcatheter locoregional i.a. and systemic i.v. administration of 5-fluorouracil (FU) at 12 dose-rate schedules: 25, 50 and 100 mg/kg; bolus, 1, 5 and 24 h infusions. In experiment A tumor (62/67 animals) as well as liver and kidney (56/67 animals) were excised 1 h after a single bolus or 1 h infusion or at the end of 5 and 24 h infusions. (19)F-NMR spectroscopy at 11.7 T was used to quantitate FU and its metabolites in ca. 1 g of tissue at 4 degrees C. In experiment B analogous FU treatments were repeated for 5 days (rats 80+11 controls). Tumor volumes vs time, various blood parameters and survival times were recorded, and a log growth rate parameter log GR, a response index RI, and a toxicity index TI were calculated. The i.a. vs i.v. ratios for tumor concentrations of FU and total anabolites (F-Nucl) were >1 for nearly all treatments and increased with infusion time at the higher doses. F-Nucl in tumor correlated linearly with total fluorine concentration (Tot. F range 30-1100 nmol/g) over all treatments (r=0.92, slope=0.45, p<0.0001). For non-bolus i.v. treatments [FU+F-Nucl] decreased linearly with decreasing FU dose rate (r(2)=0.74, zero intercept), while i.a. treatments showed non-linear behavior. For non-bolus treatments the mean log GR per treatment group showed a negative correlation (r=-0.87) with log[F-Nucl]. The most effective non-toxic treatments were 25 mg/kg over 5 or 24 h; the i.a. route was superior to i.v. on the basis of [FU+F-Nucl], RI, the reduction in log GR, and Kaplan-Meier survival statistics. For liver and kidney Tot. F (>83% FU catabolites) reached ca. 3-4 and 6-7 micromol/g, respectively, at the highest dose rates for either route; F-Nucl were detected only for Tot. F>500 nmol/g and increased exponentially as Tot. F increased (toxic treatments). The concentrations of the main catabolite (alpha-fluoro-beta-alanine, FBAL) in tumor did not correlate with Tot. F but rather with FBAL levels in kidney (r=0.90, all treatments), indicating that uptake of liver-derived FBAL from the circulation is the major source of FBAL in tumor.     

选择性髂内动脉插管灌注对盆腔恶性肿瘤介入性治疗的手术研究与探索

本文旨在探讨盆腔恶性肿瘤的介入性治疗问题。对45例患有盆腔恶性肿瘤的患者,采用Seldinger法,经双侧股动脉插管,先端选择性导入对侧髂内动脉;或一侧导入肠系膜下动脉,另侧导入髂内动脉,留置导管12小时,使用突击剂量持续灌注化疗药物。并经手术、B超、CT、内窥镜及指检等方法进行化疗前后的对比观察。结果:其中病灶消失持续1个月以上者9例、病灶缩小50％以上并持续超过一个月者23例、缩小不足50％且增大未达25％者9例、增大超过25％以上者4例,总有效率为71.1％。10例患者出现了脱发及皮肤色素沉着,1例患者出现下肢动脉栓塞,10例出现了不同程度的消化道反应等。结论:本法损伤小,操作简便安全,可多次重复术式:选择性强,药效持久均衡且毒副作用小;可提高手术切除率,也为不能手术的癌肿提供一种较理想的治疗手段。     

Genetic and teratogenic effects of cancer treatments on gametes and embryos

Male and female germ cells vary in their sensitivity to the mutagenic effects of chemotherapy and radiotherapy, depending on their stage of maturation and the agent used. Although sperm DNA damage exists following treatment, no increase in genetic defects or congenital malformations was detected among children conceived to parents who have previously undergone chemotherapy or radiotherapy. The use of assisted reproductive technologies and micromanipulation techniques might increase this risk; hence caution should be exercised. In female cancer patients, miscarriage and congenital malformations are not increased following chemotherapy. However, when IVF and embryo cryopreservation is practised between or shortly after treatment, possible genetic risks to the growing oocytes exist, and hence the babies should be screened. During pregnancy, the potential teratogenic effects of chemotherapy influence the choice and timing of therapy. Termination is usually recommended in the first trimester. Second- and third-trimester exposure does not usually increase the teratogenic risk and cognitive development, but it may increase the risk of poor obstetric outcome and fetal myelosuppression. During the first two weeks after fertilization of the embryo, radiation is lethal but not teratogenic. High doses of radiation during pregnancy induce anomalies, impaired growth and mental retardation, and there may be an increased risk of childhood leukaemia and other tumours in the offspring.     

Mitoxantrone combined to vincristine,cyclophosphamide and fluorouracil in advanced breast cancer

Summary In our wide experience of treating advanced breast carcinoma with chemotherapy, the combination of doxorubicin (DOX), vincristine (VCR), cyclophosphamide (CPM) and fluorouracil (FU) gave a complete plus partial response rate of over 60%, with 100% alopecia and frequent cardiac toxicity depending on total dose.After the EORTC Clinical Screening Group phase II trial we have conducted an expected difference method comparative phase II trial using the combination DOX, VCR, CPM, FU and the combination of MTX (10mg/m²), VCR, CPM and FU on a population of 50 breast carcinoma patients similar to those taking part in the first study.The reasons for similarity of action will be presented and discussed.     

Additive cytotoxicity of adriamycin and a naturally occurring growth inhibitor extracted from bovine aorta

A factor of nominal molecular weight 6K–10K Daltons, isolated from bovine aorta, has previously been shown to inhibit neovascularization and tumor growth in vivo and the growth of some tumor cells as well as endothelial cells in culture. This factor, termed A-10, was tested alone and in combination with Adriamycin against TA3Ha mammary adenocarcinoma cells in tissue culture. It was found to have cytotoxicity additive to that of Adriamycin in inhibiting the growth of these cells. In vitro and animal studies show that the sequence of Adriamycin A-10 is superior to either agent alone in delaying the appearance of palpable tumors after subcutaneous injection of 10⁵ pre-treated tumor cells in the tail of strain A mice. While the growth rate of the primary tumor was not affected by such treatment, survival was prolonged to a greater degree by the this sequence than by either of these agents used alone. A-10 treatment reduced the number of metastases to the adrenal gland but not to lung, liver, or lymph nodes. It did, however, reduce the size of metastases to para-aortic lymph nodes.     

Radiotherapy and combination chemotherapy with carmustine,vincristine, and procarbazine (BVP) in primary brain tumors

Summary 26 patients with astrocytoma grade 11–111, and 36 with malignant glioma (astrocytoma grade IV or glioblastoma) were submitted three days after surgery to a cycle of combination chemotherapy, including BCNU, VCR, PCZ (BVP). Eighteen days after surgery, patients received 40 Gy (astrocytoma grade 11–111) or 45 Gy (malignant glioma) of megavoltage whole-brain irradiation, with an additional boost to the tumor bed of 20 Gy, delivered in 6 weeks. Vincristine was injected weekly during radiotherapy. At the end of radiotherapy, patients received BVP every 6 weeks for at least 8 cycles or until a recurrence or progressive disease. Performance status of grade 1 or 2 was achieved in 15 (60%) and in 5 (20%), respectively, of patients with astrocytoma grade 11–111 after 6 months, and in 6 ps. (29%) and in 9 ps. (42%) after 12 months of follow-up. Only 2 (5.5%) and 18 (64%) patients with malignant glioma achieved a performance status of grade 1 or 2 after 6 months, and these proportions are 6% and 35%, respectively, after 12 months. After a 5-year follow-up, 59% of patients with astrocytoma are still alive, with a median survival time of 60+ months, whereas only 4% of patients with malignant glioma are alive, with a median of 11.2 months.