国产盐酸拓扑替康治疗小细胞肺癌临床观察

目的:评价国产拓扑替康治疗小细胞肺癌(SCLC)的临床疗效和不良反应。方法:初治和复治患者26例。拓扑替康单药治疗剂量为1.2mg/(m2·d),联合剂量为1.0mg/(m2·d),静脉滴入30min,连用5d。联合卡铂剂量为350mg/m2,21d为1个周期,2个周期评价疗效。结果:26例中,25例可评价疗效。CR1例,PR17例,有效率72％。初治的有效率为80％,复治的有效率为54％。3例脑转移的患者,2例PR。主要毒副反应为骨髓抑制,Ⅲ-Ⅳ度中性粒细胞减少19例,Ⅲ-Ⅳ度血小板减少11例。非血液毒性较轻,可耐受。结论:拓扑替康单药治疗复发SCLC疗效确切,联合卡铂可以耐受,疗效增加。主要的毒副反应是中性粒细胞和血小板减少。     

拓扑替康联合顺铂治疗卵巢癌22例疗效观察

卵巢癌早期诊断率低,患者就诊时往往已为中晚期,全身化疗仍然是治疗的主要方法。我们以国产拓扑替康(TPT)联合顺铂(DDP)治疗22例卵巢癌患者,总结报道如下。1临床资料1.1一般资料2002年8月16日～2005年10月22日,鞍山市中心医院肿瘤内科应用TPT联合DDP治疗经手术后病理学确诊的22     

大剂量异环磷酰胺联合方案治疗青少年晚期软组织肉瘤

研究大剂量异环磷酰胺(IFO)治疗多柔比星(ADM)和常规剂量IFO失败的青少年晚期软组织肉瘤的疗效及不良反应。对27例青少年晚期软组织肉瘤(术后化疗10例,进展期患者17例)采用IFO总量12g/m2持续静脉滴注6d治疗,每3周为1个疗程。进展期17例患者CR5例,PR2例,总有效率41.18%,随访4~48个月,中位生存期(22±3.35)个月,中位缓解时间(7.00±1.75)个月。主要不良反应为骨髓抑制,Ⅲ、Ⅳ度中性粒细胞减少占48.57%。初步研究结果提示,大剂量IFO治疗青少年晚期软组织肉瘤有一定的疗效,对常规ADM及IFO治疗失败后可作为挽救治疗方法。     

盐酸拓扑替康治疗34例小细胞肺癌的临床疗效观察

为了观察盐酸拓扑替康(和美新)治疗小细胞肺癌(small-cell long cance,SCLC)的疗效及毒副反应.对经病理组织学或细胞学确诊的34例SCLC患者予以盐酸拓扑替康1.5 mg/(m2·d),静脉滴入,持续30 min,连用5 d,21 d为1个周期,至少2个周期以上.34例患者中,CR 2例(5.88%),PR 13例(38.23%),NC 10例(29.41%),PD 9例(26.47%),总有效15例(44.12%).初治者8例,有效4例(4/8).复治者26例,有效11例(42.31%),中位生存期27周.毒性反应以白细胞减少及胃肠道反应常见.初步研究结果提示,单用盐酸拓扑替康治疗SCLC有较好的疗效,且毒性小,可以耐受和易控制.     

异环磷酰胺与羟基喜树碱联合治疗中晚期难治性非小细胞肺癌的疗效观察

非小细胞肺癌(non-small cell lung cancer,NSCLC)约占肺癌的80%,且大多数确诊时已属ⅢB或Ⅳ期,失去手术治疗机会。化疗在NSCLC的治疗中占很重要的地位,特别是含铂类的联合化疗方案化疗疗效得到公认与肯定。但对铂类耐药及化疗后病情进展的难治性NSCLC治疗相当棘手。我们采用异     

依立替康联合顺铂二线治疗小细胞肺癌的临床观察

为观察依立替康(lrinotecan,CPT-Ⅱ)联合顺铂(DDP)二线治疗小细胞肺癌(small-cell lung cancer,SCLC)的疗效和不良反应,对22例既往经一线化疗方案治疗失败的SCLC患者采用CPT-Ⅱ 60 mg/m2,静脉滴入,d1、d8、d15;DDP 60 mg/m2,静脉滴入,d1化疗.28 d为1个周期,至少完成2个周期以上.22例患者中除1例出现Ⅳ度腹泻退出化疗,21例患者均完成所需周期化疗.其中1例CR,8例PR,有效率(CR+PR)42.9%(9/21).常见治疗毒性为乙酰胆碱综合征(9.1%,2/22)、延迟性腹泻(18.2%,4/22)、Ⅱ～Ⅲ度白细胞减少(81.8%,18/22)和Ⅱ～Ⅲ度中性粒细胞减少(72.7%,16/22)、仅1例出现Ⅳ度腹泻,主要为血液学毒性.初步研究结果提示,CPT-Ⅱ联合DDP作为二线化疗方案治疗SCLC有效,毒副反应可以耐受.     

拓扑替康诱导卵巢癌细胞自噬的实验研究

目的:检测拓扑替康(TPT)对卵巢癌OVCAR3细胞的增殖抑制作用,观察TPT诱导OVCAR3细胞自噬现象,初步探讨其发生的可能机制。方法:采用不同浓度的TPT处理卵巢癌OVCAR3细胞,MTT法测定TPT对OVCAR3细胞增殖的抑制作用,吖啶橙(AO)染色观察酸性小体(AVO)形成,MDC荧光染色检测自噬囊泡。免疫印迹法检测TPT对OVCAR3细胞LC3-Ⅱ和Beclin1蛋白的影响。结果:TPT对OVCAR3细胞生长有显著的抑制作用,且此作用呈明显的剂量依赖性,IC50为0.057μg/mL。TPT可诱导OVCAR3细胞产生AVO。MDC荧光染色显示,TPT可诱导OVCAR3细胞产生自噬囊泡。采用0.05μg/mL TPT处理OVCAR3细胞24h后,免疫印迹法显示,随着时间的推移LC3-Ⅱ和Beclin1蛋白水平表达个逐渐增加,提示TPT诱导的OVCAR3细胞自噬可能与Bec-lin1蛋白有关。结论:TPT对OVCAR3细胞有显著的抑制作用,TPT可以诱导OVCAR3细胞发生自噬,TPT诱导OVCAR3细胞自噬可能与Beclin1蛋白上调有关。     

依立替康联合顺铂二线治疗小细胞肺癌的临床观察

为观察依立替康(lrinotecan，CPT-Ⅱ)联合顺铂(DDP)二线治疗小细胞肺癌(small-cell lung cancer，SCLC)的疗效和不良反应，对22例既往经一线化疗方案治疗失败的SCLC患者采用CP-Ⅱ60mg／m^2，静脉滴入，d1、d8、d15，DDP60mg／m^2，静脉滴入，d1化疗。28d为1个周期，至少完成2个周期以上。22例患者中除1例出现Ⅳ度腹泻退出化疗，21例患者均完成所需周期化疗。其中1例CR，8例PR，有效率(CR PR)42．9％(9／21)。常见治疗毒性为乙酰胆碱综合征(9．1％，2／22)、延迟性腹泻(18．2％，4／22)、Ⅱ～Ⅲ度白细胞减少(81．8％，18／22)和Ⅱ～Ⅲ度中性粒细胞减少(72．7％，16／22)、仅1例出现Ⅳ度腹泻，主要为血液学毒性。初步研究结果提示，CPT-Ⅱ联合DDP作为二线化疗方案治疗SCLC有效，毒副反应可以耐受。     

30例儿童神经母细胞瘤的综合治疗疗效观察

背景和目的：神经母细胞瘤是儿童期常见实体肿瘤之一。主要的治疗手段是手术、化疗和放疗等综合治疗,然而晚期患者治愈率仍然低,如何提高治愈率值得进一步研究。本研究主要总结我中心治疗儿童神经母细胞瘤的疗效,探讨合理的治疗策略。方法：回顾性分析我科采用化疗联合手术或放疗综合治疗的30例7个月--13岁的神经母细胞瘤患者临床资料。Evan分期：Ⅱ期2例,Ⅲ期12例,Ⅳ期15例,ⅣS期1例;化疗主要采用CAV与EP方案交替。(CAV：CTX 750mg／m^2d1,VCR 1．5mg／m^2d1,ADR 50mg／m^2d1;EP：VM26或VP-16 60mg／m^2d1-5,DDP 20mg／m^2d1-5)。化疗4～8疗程后能手术尽量手术,术后继续化疗或放疗;不能手术则继续化疗。ⅣS期则仅用CTX加VCR化疗。结果：30例患者单纯化疗获得完全缓解2例(6．7％),部分缓解21例(70％),无变化6例(20％),PD 1例(3．3％),化疗总有效率(CR PR)76．7％(23例)。21例部分缓解者中,9例(43％)获得手术切除,其中4例手术切除获得CR,1例行放疗获得CR。全组2年总生存率47．8％,Ⅱ／ⅣS期100％,Ⅲ期34％,Ⅳ期22％。CAV方案Ⅲ／Ⅳ级骨髓抑制占41．2％,EP方案则占26．6％。结论：化疗联合手术或放疗是治疗神经母细胞瘤的主要方法,CAV／EP方案是目前治疗神经母细胞瘤疗效较好的方案之一,毒性可耐受,晚期神经母细胞瘤预后差,值得进一步研究和探讨新的治疗方法。     

Second malignancies in children with neuroblastoma after combined treatment with 131I-metaiodobenzylguanidine

BACKGROUND: (131)I-metaiodobenzylguanidine ((131)I-MIBG) is selectively taken up by cells of neural crest origin, allowing targeted radiotherapy of tumors such as neuroblastoma (NB) and pheochromocytoma. Radiotherapy may provide additional benefits in the treatment of NB, with moderate side effects such as hematologic and thyroid toxicity. However, with longer follow-up, other complications might occur. We describe our experience with second cancers occurring in children treated with (131)I-MIBG and chemotherapy. METHODS: The clinical records of 119 consecutive NB cases treated with (131)I-MIBG at a single institution between 1984 and 2001 were reviewed for the occurrence of a second malignant neoplasm (SMN). RESULTS: Overall, five cases of SMN occurred in the study patients. In particular, two cases of myeloid leukemia, one of angiomatous fibrous histiocytoma, one of malignant schwannoma, and one case of rhabdomyosarcoma were detected. The schwannoma and the rhabdomyosarcoma developed within the residual neuroblastic mass after first-line therapy. CONCLUSIONS: Should (131)I-MIBG treatment become more broadly employed in the therapeutic strategy for neuroblastoma, the risk of second cancer will have to be taken into consideration. The organization of an international registry of subjects treated with (131)I-MIBG might better define the frequency and features of second malignancies following this radiometabolic approach.     

Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer.

PURPOSE: Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were evaluated in a randomized, multicenter study of patients with small-cell lung cancer (SCLC) who had relapsed at least 60 days after completion of first-line therapy. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV (cyclophosphamide 1,000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg) infused on day 1 every 21 days (n = 104). Eligibility included the following: bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of less than or equal to 2, and adequate marrow, liver, and renal function. Response was confirmed by blinded independent radiologic review. RESULTS: Response rate was 26 of 107 patients (24.3%) treated with topotecan and 19 of 104 patients (18.3%) treated with CAV (P = .285). Median times to progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P = .552). Median survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P = .795). The proportion of patients who experienced symptom improvement was greater in the topotecan group than in the CAV group for four of eight symptoms evaluated, including dyspnea, anorexia, hoarseness, and fatigue, as well as interference with daily activity (P< or =.043). Grade 4 neutropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV courses (P<.001). Grade 4 thrombocytopenia and grade 3/4 anemia occurred more frequently with topotecan, occurring in 9.8% and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively (P<.001 for both). Nonhematologic toxicities were generally grade 1 to 2 for both regimens. CONCLUSION: Topotecan was at least as effective as CAV in the treatment of patients with recurrent SCLC and resulted in improved control of several symptoms.     

Very high dose cyclophosphamide with imidazole carboximide and vincristine sulfate in the treatment of stage IV neuroblastoma

To address the problem of drug dosage as a limiting factor for successful chemotherapy, seven patients with Stage IV neuroblastoma were treated with very high dose cyclophosphamide with imidazole carboximide (DTIC) and vincristine sulfate in conjunction with intensive supportive care. None of the patients experienced a complete response. The major toxicity was myelosuppression, complicated by significant infections. Toxicity was significantly more severe in this study than in similar regimens using these three drugs at conventional doses. Although the number of patients in this study was small and most had received prior therapy, our data do not support the efficacy of very high dose cyclophosphamide in the treatment of Stage IV neuroblastoma.     

Smooth-muscle antibodies in children with neuroblastoma

Smooth-muscle antibodies (SMA) were detected in 16 of 18 (89%) children with neuroblastoma and in 43 of 172 (25%) pediatric hospital patients without malignancies. The SMA were mainly of the IgG class. The most common immunofluorescence pattern was SMA-V (vessel) and titers did not exceed 1:160. Absorption and immunodiffusion tests with action (from rabbit skeletal muscle) showed that the SMA associated with neuroblastoma are mainly directed against actin, although different antigen specificities (myosin, meromyosin) are probably involved in some cases. In both chronic active hepatitis and neuroblastoma, SMA would represent a specific response to intracellular contractile proteins (mainly actin) induced by tissue damage. A feedback role in controlling cellular proliferation has been postulated for experimentally raised SMA. This would be relevant in cases of malignancy.     

Biochemical monitoring of children with neuroblastoma

In this article, a short review is given of the biochemical aspects of diagnosis, estimation of prognosis and follow-up of neuroblastoma in children. The importance of determination of patterns of DOPA-metabolites, rather than single metabolite assay, is stressed and illustrated by patient cases. Also the relevance of urinary cystathionine and beta-amino-isobutyric acid is indicated.     

Prognosis in Black children with neuroblastoma.

Thirty white and 15 black children with neuroblastoma were compared with respect to survival. Patient age and tumor stage at diagnosis were similar in the two groups, as was duration of symptoms prior to diagnosis. There was no significant difference between the white and black children in regard to median duration of survival or percentage of long-term survivors. The results of this study indicate that race is not a factor in the prognosis of this tumor.     

Topotecan in the treatment of elderly patients with relapsed small-cell lung cancer

BACKGROUND: Almost 70% of all patients with lung cancer in the United States are>65 years of age, and the incidence of small-cell lung cancer (SCLC) increases with age until the eighth decade of life. However, elderly patients are underrepresented in clinical trials and are often suboptimally treated. The validity of age as a prognostic factor for toxicity or survival remains controversial. PATIENTS AND METHODS: To investigate the safety and efficacy of topotecan (an approved treatment for relapsed SCLC) in older patients, we performed a retrospective analysis in patients >or= 65 years of age versus patients < 65 years of age from 5 large topotecan trials. In all 5 trials, patients received topotecan 1.5 mg/m2 per day via a 30-minute intravenous infusion on days 1 through 5 of a 21-day cycle. Efficacy and tolerability outcomes were assessed for both age groups. RESULTS: Topotecan was similarly tolerated in both age groups, with generally manageable hematologic toxicity. The incidence, duration, and onset of severe hematologic toxicities did not vary significantly with age. In the<65 age group, grade 4 neutropenia and leukopenia were reported in 72% and 32% of patients, respectively; in the >or= 65 age group, grade 4 neutropenia and leukopenia were reported in 77% and 31% of patients, respectively. Grade 4 thrombocytopenia was less common in the<65 age group. Nonhematologic toxicities, median time to progression, and overall survival were comparable between groups. CONCLUSION: This is the first demonstration of the safety and efficacy of topotecan in older patients with recurrent SCLC. Future studies are needed to fully characterize the role of topotecan in the treatment of older patients.     

Risk factors for scoliosis in children with neuroblastoma

PURPOSE: To determine the risk factors for scoliosis in children treated for neuroblastoma. METHODS AND MATERIALS: From 1957 to 1997, 58 children with neuroblastoma were treated at one institution and have survived a minimum of 5 years. There were 35 boys and 23 girls with a median age of 6 months (range, 2 weeks to 15 years) at initial diagnosis. Primary site was located in the adrenal gland in 25 (43.1%), abdominal/nonadrenal in 16 (27.6%), thoracic in 12 (20.7%), cervical in 3 (5.3%), and pelvic region in 2 (3.5%). The International Neuroblastoma Staging System (INSS) stage was Stage 1 in 10 (17.2%), Stage 2A in 7 (12.1%), Stage 2B in 5 (8.6%), Stage 3 in 22 (37.9%), Stage 4 in 4 (6.9%), and Stage 4S in 10 (17.2%). Thirty-three (56.9%) received chemotherapy whereas 5 (8.6%) had a laminectomy as part of the surgical procedure. Twenty-seven (46.6%) received radiotherapy (RT). Beam energy was 1.25 MV in 11 (41%), 250 kV in 10 (37%), 4 MV in 4 (15%), and 6-MV photons in 1 patient. One patient received 300 cGy in 1 fraction total skin RT using 6-MeV electrons. For the remaining patients, fraction size was 100 cGy in 6 (22%), 150-180 cGy in 11 (41%), 200 cGy in 4 (15%), and 250-300 cGy in 3. Three patients had total body irradiation at 333 cGy for 3 fractions. For all children who received RT, median total dose was 2000 cGy (range, 300-3900 cGy). Patients who were treated with RT had plain films of the irradiated area every 1 to 2 years until at least the age of puberty. Median follow-up was 10 years (range, 5-46 years). RESULTS: The overall 5-, 10-, and 15-year scoliosis-free rates were 87.6%, 79.0%, and 76.0% respectively. Twelve (21%) developed scoliosis at a median time of 51 months (range, 8-137 months). The degree of scoliosis was mild (< or =20 degrees ) in 8 (67%). Four had scoliosis ranging from 30 degrees to 66 degrees ; 3 of these patients required surgical intervention, whereas 1 had an underlying Duchenne muscular dystrophy which manifested itself 8 years after diagnosis of neuroblastoma. Median time to scoliosis was 23 months (range, 8-54 months) in children who had a laminectomy. On multivariate analysis, both history of laminectomy (p = 0.0005) and use of RT (p = 0.0284) were found to be risk factors for development of scoliosis. Gender, age at diagnosis, INSS stage, primary site, and use of chemotherapy were not found to be significant. Both RT fraction size and beam energy were also not significant, but increasing total RT dose was found to be significant (p = 0.0039). The 15-year scoliosis-free rates were 20% for children who had a laminectomy and 81.3% for those who did not have a laminectomy. The 15-year scoliosis-free rates for children treated with RT doses 0 cGy, 1-1750 cGy, 1751-2300 cGy, and >2300 cGy were 91.7%, 87.5%, 51.4%, and 44.4% respectively. CONCLUSIONS: Treatment-related factors, namely laminectomy and radiotherapy, were found to increase the risk of scoliosis in patients with neuroblastoma. Children who had a laminectomy were more likely to manifest scoliosis earlier. Increasing RT dose was found to impact adversely on the development of scoliosis.