长春瑞宾联合顺铂治疗进展期非小细胞肺癌50例临床观察

目的观察长春瑞宾联合顺铂治疗进展期非小细胞肺癌的疗效及毒副反应。方法长春瑞宾25mg／m^2d1,8，静脉滴注，顺铂25mg／m^2，d1～3，静脉滴注，21天为1周期，至少两周期以上评价疗效。结果50例可评价疗效的患者中，完全缓解（CR）2例，部分缓解（PR）19例，总有效率为42．0%（21／50），疗效分析显示Ⅲb期有效率为44．8％，Ⅳ期有效率为38．1％（x^2=0．227，P=0．634）。50例患者中位生存期（MST）10．0个月，其中Ⅲb期MST13．6个月，Ⅳ期MST8．6个月（X^2=0．239，P=0．601）。50例患者1年生存率42．0%，其中Ⅲb44．8％（13／29），Ⅳ期38．1％（8／21）（X^2=0．245，P=0．596）。主要毒副反应为骨髓抑制和消化道反应，白细胞减少为76.0％（Ⅱ～Ⅳ级为28．0％），血小板减少为42．0%（Ⅲ～Ⅳ级为2．0％），消化道反应为72．0％（Ⅲ～Ⅳ级为12．0％），静脉炎为48．0％（Ⅲ～Ⅳ级为6．0%），脱发为46．0％（Ⅲ～Ⅳ级为6．0%）。结论长春瑞宾联合顺铂治疗进展期非小细胞肺癌为有效的一线联合化疗方案。     

Combination chemotherapy with S-1 and cisplatin for non-small cell lung cancer

S-1 is a newly developed oral anti-tumor agent, which contains 5-chloro-2, 4-dihydroxypyridine and potassium oxonate to strengthen biological activities of 5-fluorouracil. Response rate of S-1 for advanced non-small cell lung cancer was reported to be 12.5-22%. Response rate of combination chemotherapy with S-1 plus cisplatin (CDDP) was reported to be 47%, and the median survival time was 11 months. Adverse events of the combination chemotherapy were milder than other combination chemotherapy described before. Therefore, S-1 plus CDDP combination chemotherapy is a future candidate for phase III clinical study.     

Combination chemotherapy without cisplatin in the treatment of advanced non-small cell lung cancer

Cisplatin-based combinations are standard regimens in the treatment of advanced non-small cell lung cancer. Survival improvement has been achieved using this therapy. However, the high toxicity induced by cisplatin-based doublets urges the research of alternate treatments. Newest cytotoxic compounds yield a better efficacy-toxicity ratio. Platinum-free doublet regimens based on new drugs are expected to offer the patient an improved survival without decreasing his quality of life. Treatment-allocated time and period with high grade toxicity could be considered as wasted from the patient point of view. QUALY methods based on time without symptoms and toxicity allow the accurate evaluation of this end-point. This brief state-of-the-art deals with methodological statements highlighted by the first publications of randomized studies comparing non-platinum-based doublets with either single-drug chemotherapy or standard cisplatin-based doublets.     

Combination chemotherapy of ifosfamide, cisplatin and vindesine for non-small cell lung cancer

Twenty patients with advanced non-small cell lung cancer were treated with a combination chemotherapy consisting of ifosfamide (IFX), cisplatin (CDDP) and vindesine (VDS). The treatment schedule was IFX 1.3 g/m2 i.v., on days 1-5, CDDP 20 mg/m2 i.v., on days 1-5, and VDS 3 mg/m2 i.v., on days 1 & 8, and, in principle, the regimen was repeated every 4 weeks. Of 19 evaluable patients, there were 1 CR, 7 PR, 10 NC and 1 PD, with an overall response rate of 42.1%. The median duration of responses was 7.45 months, and the median survival time of all patients was 13.2 months. The major toxicities occurring were hematologic toxicity, alopecia, gastrointestinal toxicity and peripheral neuropathy. Hematologic toxicity was severe and was judged to be dose limiting, but clinically manageable. These results indicate that this combination chemotherapy is active against non-small cell lung cancer and deserves further studies.     

Surgical adjuvant chemotherapy in non-small cell lung cancer

In two different controlled prospective randomized trials the Lung Cancer Study Group has shown that adjuvant CAP chemotherapy is effective in prolonging the disease-free survival. These studies indicate that the adjuvant chemotherapy has its effect by way of diminishing systemic recurrences and that the adjuvant therapy is more effective in non-squamous than in squamous disease. In addition, the benefit of the treatment is more apparent in patients with more advanced, though resectable, disease. It is also becoming clear that chemotherapy either alone or in combination with radiation therapy can result in relatively high response rates in patients with disease localized to the thorax. Indeed, many of these individuals can then undergo surgical resection. It remains to be determined, however, whether or not this preoperative therapy will be effective in prolonging survival. In the future it is quite likely that optimum therapy will involve the use of preoperative treatment either with chemotherapy alone or a combination of chemotherapy and radiation therapy, followed postoperatively with adjuvant chemotherapy with a non-cross resistant regimen. In addition, a major problem is brain recurrences. Indeed the brain was the most frequent site of first recurrence systemically in many of these studies. Thus, more effective therapy directed at CNS disease will have to be developed before major breakthroughs can be anticipated in the surgical adjuvant therapy of lung cancer.     

艾迪注射液对晚期非小细胞肺癌NP方案化疗的影响

Objective:To evaluate the effects of Aidi injection on vinorelbine plus cisplatin(NP) chemotherapy for advanced non-small cell lung cancer(NSCLC).Methods:Ninety eight patients with advanced NSCLC were randomized to receive either NP alone or NP plus Aidi injection every 3 weeks.The primary endpoint was overall survival;secondary endpoints included overall response rate,time to progression,and safety.Results:The median overall survival time was 11.6 months in NP plus Aidi-treated patients and 10.1 months in NP alone-treated ones,and 1-and 2-year survival rates were higher in the former(47% and 22%) than the latter(42% and 15%).The overall response rates in Aidi injection plus NP-treated patients tended to be higher but not statistically significant compared with NP alone-treated ones.The occurrence rates of grades 3 or 4 toxicities,e.g.fatigue,nausea,vomiting,appetite loss,leucopenia,thrombocytopenia and anemia,were lower in Aidi injection plus NP-treated patients than NP alone-treated ones,although not significantly different between them.Conclusion:Aidi injection promotes NP chemotherapeutic effects,reduces the toxicities,and improves the patients' tolerance to chemotherapy as well.It may be an effective adjunct to chemotherapy in patients with NSCLC.     

A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non-small cell lung cancer

BACKGROUND: A combination of cisplatin and vinorelbine chemotherapy is effective in cases of advanced non-small cell lung cancer, but the optimum administration schedule for both drugs has not yet been defined. The aim of this study was to determine the maximum dose of vinorelbine that can be tolerated while receiving a fixed dose of cisplatin every 3 weeks and to observe the response in Japanese patients with advanced non-small cell lung cancer who had not previously received chemotherapy. METHODS: Cisplatin was given at a dose of 80 mg/m2 on day 1. Vinorelbine was administered on days 1 and 8 at a starting dose of 25 mg/m2 that was then increased by 5 mg/m2 increments. This treatment was repeated every 3 weeks. RESULTS: Twenty-one patients received a total of 54 chemotherapy cycles consisting of three different vinorelbine dosages. Toxicity and efficacy were evaluated in all of the patients. The main dose-limiting toxicity was neutropenia. Grades 3-4 leukopenia and neutropenia were observed in 57% and 86% of all cycles, respectively. These conditions were reversible and did not result in death from toxicity. The most severe non-hematological toxicity symptom was a grade 3 infection and reaction at the site of injection. The maximum tolerated dose of vinorelbine was 35 mg/m2. The objective response was noted in one of six patients at dose level 1, in four of 12 patients at dose level 2 and in two of three patients at dose level 3. CONCLUSION: The recommended doses were 80 mg/m2 for cisplatin and 30 mg/m2 for vinorelbine. The combination of cisplatin and vinorelbine repeated every 3 weeks is well tolerated and has shown promising anti-tumor activity against non-small cell lung cancer.     

去甲长春花碱联合顺铂治疗中晚期非小细胞肺癌的临床研究

目的　评价去甲长春花碱 (vinorelbine ,NVB)联合顺铂 (cisplatin ,DDP)治疗非小细胞肺癌的近期疗效、毒副反应、中位生存期及生存率。方法　对 2 2 0例不能手术的非小细胞肺癌患者采用NVB联合DDP化疗 ,NVB 2 5～ 3 0mg/(m2 ·d) ,第 1、5 (或第 8)天 ;DDP 60～ 80mg/(m2 ·d) ,第 2天 ,2 8天为一周期。完成两周期以上评价疗效 ,观察毒副反应并进行随访。结果　全组有效率 (RR)为 3 0 .9% ( 68/2 2 0 ) ,初治者有效率为 3 1.3 % ( 5 1/163 ) ,复治者为 2 9.8% ( 17/5 7)。全组中位生存期 8.3月 ,1年生存率 3 9.2 3 % ,2年生存率 19.3 1% ,3年生存率 6.3 2 %。主要毒性反应为骨髓抑制和消化道反应。结论　NVB联合DDP是治疗非小细胞肺癌有效且耐受性好的方案 ,骨髓抑制为其剂量限制性毒性。     

Phase II study of docetaxel and vinorelbine as adjuvant chemotherapy for resected non-small cell lung cancers

Purpose

For patients with resected stage II–III non-small cell lung cancers (NSCLCs), adjuvant cisplatin-based chemotherapy improves survival over surgery alone. For cisplatin ineligible patients, there is no standard adjuvant option. We evaluated drug delivery and toxicity of docetaxel and vinorelbine in patients who could not receive cisplatin.

Methods

Patients with completely resected stage IB–III NSCLCs were treated with up to 4 cycles of docetaxel and vinorelbine at the recommended phase II dose. The primary endpoint was drug delivery compared to historical delivery of adjuvant cisplatin plus vinorelbine. Secondary endpoints were toxicity and feasibility.

Results

Twenty-five patients were enrolled. Overall, 13/25 (52 %, 95 % CI 34–70) completed 4 cycles, and 19/25 (76 %, 95 % CI 60–87) completed ≥3 cycles. Twenty of 25 patients (80 %) experienced a Grade 3 or 4 adverse event.

Conclusions

Delivery of this dose and schedule of docetaxel and vinorelbine was difficult with a dose delivery comparable to cisplatin plus vinorelbine, and cisplatin plus docetaxel, used in this setting.     

Adjuvant chemotherapy for radically resected non-small cell lung cancer: a retrospective analysis of 311 consecutively treated patients

BACKGROUND: The impact of adjuvant chemotherapy (CT) in the management of resectable non-small cell lung cancer (NSCLC) is highly debated. The aim of the study was to evaluate the outcome of this category of patients, treated at the Military Hospital Bucharest (surgery) and Institute of Oncology Bucharest (CT). PATIENTS AND METHODS: We retrospectively analyzed the survival data according to various patients' characteristics, the corresponding pattern of relapses, along with the data concerning the CT program. RESULTS: A number of 311 consecutively treated patients (pts.), between January 1994 and October 2002, were evaluated. All patients were radically resected and received adjuvant CT. Chemotherapy was planned to be cisplatin-based and to be delivered for six cycles. In addition, 141 pts. (45%) received post-operative irradiation (RT). demographics: sex, M 252 (81%)/F 59 (19%) and median age: 58 (range 31-75). Stage: I 55 (17%), II 71 (23%), III A 140 (45%) and III B 45 (15%). After a median follow-up of 46 months, the overall median survival (MS), considering all the patients, was 42 months and the 5-year survival rate (5-year SR) was 44%. According to stage, MS and 5-year SR were as follows: Stage I = not reached/94%; Stage II = 54 months/59%; Stage III A = 28 months/37% and Stage III B= 18 months/27%. According to lymph node status, the MS was not reached for pN-negative pts. and 26 months for pN-positive pts. (P = 0.0002), while the 5-year SR was 75% versus 35%, respectively. Platinum-based CT was delivered in 295 pts. (95%). The medium number of cycles was five. A number of 86 (28%) relapses were recorded, of which 50 (16%) were distant, 25 (8%) local and 11 (4%) distant and local. The sites of the 50 distant relapses were BRA 24 (48%), OSS 10 (20%), PUL 6 (12%) and OTH 10 (20%). CONCLUSION: Our analysis shows good long-term survival data for adjuvant CT following surgery in NSCLC, which looks comparatively superior to those communicated for surgery-only series. Pathologic invasion of the lymph nodes has a strong adverse effect on patients' outcome. The positive impact of CT in this setting is indirectly sustained by the pattern of relapses, which place the brain sanctuary on the first rank. Overall, the patients' compliance was good and we delivered a medium of five cycles of adjuvant platinum-based CT.     

Postoperative adjuvant chemotherapy for non-small cell lung cancer

Patients with completely resected non-small-cell lung cancer (NSCLC) are subjects for postoperative adjuvant treatment. Recently, several randomized trials with a large number of enrolled patients have shown that platinum-based chemotherapy has potential for improving survival among patients with completely resected NSCLC in Western countries. In Japan, uracil-tegafur was also shown to improve survival among patients with completely resected stage I adenocarcinoma. This review evaluated the role of adjuvant chemotherapy, based on the results of randomized trials and meta-analyses.     

CLINICAL EFFICACY OF VINORELBINE PLUS CISPLATIN IN ADVANCED NON-SMALL CELL LUNG CANCER

A clinical study of the efficacy of vinorelbine plus cisplatin regimen in the management of advanced NSCLC was performed in 35 patients. Five of the 35 patients failed to finish one cycle of chemotherapy with this regimen because of severe and intractable leukopenia or rapid progress of the disease. Tumor response and toxicity were evaluated in the remaining 30 cases. Results showed that, with this regimen, the objective response rate (CR PR) was 46.7%. The most common toxicity was leukopenia; other side effects included alopecia, gastrointestinal reactions, slight and transient renal and hepatic impairment and peripheral neuropathy. It suggested that vinorelbine plus cisplatin is a safe and effective regimen in the management of advanced NSCLC.     

NSCLC患者外周血淋巴细胞多药耐药基因的表达与长春瑞滨化疗疗效的相关性研究

目的：检测多药耐药基因（MDR-1）在非小细胞肺癌患者外周血淋巴细胞中的表达，探讨MDR-1的表达与肺癌的病理类型及分期的关系及与长春瑞滨联合铂类化疗疗效之间的关系。方法：采用逆转录聚合酶链反应（RT—PCR）技术检测46例非小细胞肺癌患者外周血中MDR-1的表达水平，并与30例健康对照组进行比较。非小细胞肺癌患者均采用NP方案治疗，2个治疗周期后评价疗效。结果：非小细胞肺癌组外周血淋巴细胞MDR-1阳性检出率36．95％（17／46），其中腺癌9例阳性，鳞癌7例阳性，腺鳞癌1例阳性，Ⅰ期1例阳性，Ⅱ期3例阳性，Ⅲ期7例阳性，Ⅳ期6例阳性，而健康对照组仅1例阳性。MDR-1表达阳性的非小细胞肺癌患者应用长春瑞滨联合铂类化疗的有效率明显低于MDR-1表达阴性者，差异具有统计学意义。结论：非小细胞肺癌患者外周血淋巴细胞MDR-1表达水平较高，与肺癌的病理类型及分期无关；与长春瑞滨联合铂类化疗的临床疗效具有一定的相关性，临床上可根据MDR—1表达情况，制定个体化的化疗方案。     

多西紫杉醇联合顺铂治疗79例晚期非小细胞肺癌

为观察多西紫杉醇联合顺铂(DDP)两种方案治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副反应,将79例晚期NSCLC患者随机分为3周剂量组和每周剂量组。3周剂量组:多西紫杉醇75mg/m2,d1;DDP80mg/m2。分3～5d静脉滴入,21d为1个周期。每周剂量组:多西紫杉醇35mg/m2,d1、d8、d15;DDP80mg/m2,分3～5d静脉滴入,28d为1个周期。每例患者至少应用2个周期。结果:3周剂量组和每周剂量组有效率分别为36.8%和34.1%(χ2=0.063,P=0.802),初治患者有效率分别为45.5%和46.2%,复治患者有效率分别为33.3%和28.6%。常见的毒副反应为骨髓抑制及消化道反应,反应程度以Ⅰ～Ⅲ度为主。初步研究结果提示,多西紫杉醇联合DDP治疗晚期NSCLC两种方案疗效相当,毒副反应每周剂量组较3周剂量组轻微。     

Docetaxel and cisplatin as second-line chemotherapy for advanced non-small cell lung cancer

AIMS AND BACKGROUND: Docetaxel and cisplatin are both active against non-small cell lung cancer (NSCLC). This pilot study evaluated the efficacy and toxicity of docetaxel and cisplatin as second-line chemotherapy for patients with advanced NSCLC. PATIENTS AND METHODS: Eleven patients with advanced NSCLC who had no response to platinum-based treatment or had recurrence after a partial response were enrolled (2 stage III B, 9 stage IV; 8 men, 3 women). Median age was 58 years (range, 40 to 74 years). Seven patients had an Eastern Cooperative Oncology Group performance status of 0, and four had a performance status of 1. Four weeks or more after the end of previous therapy, all 11 patients received docetaxel 60 mg/m2 and cisplatin 80 mg/m2 on day 1 every four weeks. RESULTS: Two patients (18.2%) achieved a partial response,five (45.4%) patients had stable disease, and four (36.4%) patients showed progressive disease after initiation of second-line therapy. Median survival was 277 days. Median time to disease progression was 101 days, and the one-year survival rate was 36.4%. Hematological toxicities were moderate. Grade 3 and 4 leukocytopenia and neutropenia were observed in five (45.4%) patients. Grade 3 anemia occurred in one (9 .1%) patient. No severe non-hematological toxicities were observed except grade 3 nausea in two (18.2%) patients. CONCLUSIONS: The regimen of docetaxel and cisplatin has reasonable efficacy with moderate toxicity as second-line chemotherapy for patients with previously treated, advanced NSCLC.     

NP和GP方案治疗晚期非小细胞肺癌疗效分析

目的:评价NP和GP两组化疗方案治疗晚期非小细胞肺癌(nonsmallcelllungcancer,NSCLC)的疗效和不良反应。方法:将有明确的病理学和(或)细胞学诊断的63例晚期NSCLC患者分为两组,NP组33例,国产长春瑞滨(盖诺,NVB)25mg/m2,静脉推注,d1、d8;顺铂(DDP)80～90mg/m2,静脉滴入,d1;GP组30例,吉西他滨(健择,GEM)1.25g/m2,静脉滴入,d1、d8;DDP80～90mg/m2,静脉滴入,d1。两组同时配合水化利尿,每21d为1个周期,化疗3个周期后评价疗效,化疗期间记录不良反应。结果:NP与GP方案的有效率分别为36.3%和40.0%,中位生存时间分别为12.2和12.0个月,1年生存率分别为47.2%和43.5%,2年生存率分别为21.1%和17.8%。不良反应主要为血液学毒性和恶心、呕吐。结论:NP和GP两组化疗方案在治疗晚期NSCLC的近期疗效、中位生存期、1年和2年生存率方面相近,化疗不良反应可耐受。     

诺维本联合顺铂治疗NSCLC 90例临床观察

目的 评价诺维本（ｎａｖｅｌｂｉｎｅ,ＮＶＢ）与顺铂（ｃｉｓｐｌａｔｉｎ,ＤＤＰ）联合治疗非小细胞肺癌（ｎｏｎ－ｓｍａｌｌ ｃｅｌｌ ｌｕｎｇ ｃａｎｃｅｒ,ＮＳＣＬＣ）的疗铲及毒副反应。方法 自１９９４年４月至１９９８年１２月对９０例中晚期ＮＳＣＬＣ患者进行ＮＶＢ＋ＤＤＰ联合化疗,第１、８天用ＮＶＢ２５～３０ｍｇ／ｍ＾２,第３天用ＤＤＰ６０～８０ｍｇ／ｍ＾２,每２８天为一周期,每例患者至少完成２