Tirapazamine with cisplatin and vinorelbine in patients with advanced non-small-cell lung cancer: a phase I/II study

This phase I/II study was conducted to evaluate the safety and efficacy of tirapazamine in combination with cisplatin and vinorelbine for patients with advanced-stage IIIB/IV chemonaive non-small-cell lung cancer. Seventy patients with a Karnofsky performance status of > or = 60% were included. In the phase I part of the study, 21 patients were treated on day 1 with tirapazamine (escalating doses of 260, 330, or 390 mg/m(2)), cisplatin (75 or 100 mg/m(2)), and vinorelbine (25 or 30 mg/m(2)) for a maximum of 6 cycles every 4 weeks. Vinorelbine was repeated every week. In the phase II part of the study, 49 patients were treated on day 1 with tirapazamine 390 mg/m(2), cisplatin 100 mg/m(2), and vinorelbine 30 mg/m(2). The maximum tolerated dose was not reached. Muscle cramps, vomiting, nausea, tinnitus, neutropenia, and diarrhea were the most frequently reported adverse events in the phase I part of the study. Most of these events were grade 1 or 2. In the phase II part of the study, response rate was 47%, and median survival was 50 weeks. The most frequently reported adverse event was neutropenia. Asthenia, fever, anemia, vomiting, weight decrease, nausea, and muscle cramps were also noted. For patients treated at the maximum dose, dose reductions occurred 14% of tirapazamine cycles and in 4% of cisplatin cycles. The median number of cycles was 3. This regimen has a manageable toxicity profile. Response rate and median survival suggest that this combination might be more active than the cisplatin/vinorelbine combination. This triplet is currently being evaluated in a phase III study.     

Carboplatin, ifosfamide, and vinorelbine in the treatment of advanced non-small-cell lung cancer: a phase II study

The authors evaluated the efficacy and toxicity of the combination of carboplatin, ifosfamide, and vinorelbine in the treatment of advanced non-small-cell lung cancer. From March 1994 through March 1996, 56 previously untreated patients with stage IIIB or stage IV non-small-cell lung cancer with measurable lesions and good performance status were entered in the study. The chemotherapy schedule was as follows: carboplatin 100 mg/m2 and ifosfamide 1,500 mg/m2 with mesna on days 1, 2, and 3; vinorelbine 25 mg/m2 on days 1 and 8, every 21 days; for a total of six courses. Among 55 evaluable patients there were three complete responses (5%) and 22 partial responses (40%), for a response rate of 45% (95% confidence interval, 32-59%). The median response duration was 10.3 months (range, 2.5-27.7 months), and median survival time was 11.3 months (range, 1.1-28.1 months). The survival rate at 1 year was 48%. Toxicity included hematologic toxicity in 60% of the 247 treatment cycles administered, nausea, alopecia, and neuropathy. One pathologic complete response was observed in a patient with stage IIIB disease who became operable after four courses of chemotherapy. The outpatient treatment with carboplatin, ifosfamide, and vinorelbine shows activity in advanced non-small-cell lung cancer. The toxicity was well tolerated by patients with a good performance status.     

A phase II study of a daily x4 schedule of vinorelbine plus cisplatin for advanced non-small cell lung cancer

BACKGROUND: Because dose intensity may be important as a determinant response to vinorelbine, we explored the possibility of increasing the dose intensity of vinorelbine on a daily x4 schedule. METHODS: Between February 1998 and March 1999, 31 patients with previously untreated advanced non-small cell lung cancer were enrolled. Vinorelbine 15 mg/m2 and cisplatin 20 mg/ m2 were administered intravenously daily for 4 days and repeated every 21 days. RESULTS: A total 96 cycles were administered (median 3, range 1-6); 42% of vinorelbine and 39% of cisplatin injections were dose-reduced or delayed owing to toxicity. The actual dose intensity (DI) of vinorelbine was 17.7 mg/m2/week and that of cisplatin was 24 mg/m2/week. These figures represent 88 and 90% of the theoretical DI, respectively. The overall response rate was 40% (12/30, one CR). The main toxicity was myelosuppression: granulocytopenia WHO grade 3 and 4 in 24 patients (77%) and thrombocytopenia grade 3 in two patients (6%). The non-hematological toxicity was mild and tolerable. After a median follow-up of 7.5 months (range 3-21 months), the median progression-free survival and overall survival times were 5 months (95% CI, 3.8-6.2) and 8 months (95% CI, 4.5-11.5), respectively. CONCLUSIONS: This regimen has a comparable therapeutic activity in patients with advanced lung cancers. However, despite supportive care there were excessive hematological toxicities. In view of increased toxicity and similar efficacy, this regimen is not indicated outside a clinical trial.     

长春瑞滨联合奥沙利铂治疗老年晚期非小细胞肺癌

目的:评价长春瑞滨(NVB)联合奥沙利铂(OXA)治疗老年晚期非小细胞肺癌的疗效和毒副反应。方法:对住院治疗的老年晚期肺癌患者28例,用NVB联合OXA方案化疗,NVB25mg/m2ivd1、8,OXA130mg/m2ivd1,4周重复。结果:全组28例共完成78周期化疗,PR11例,有效率39.29%,中位生存期10.3个月,1年生存率32.14%,主要毒副反应为骨髓抑制和周围神经炎。结论:长春瑞滨联合奥沙利铂治疗老年晚期非小细胞肺癌有较好疗效,毒副反应可以耐受。     

三种化疗方案治疗晚期非小细胞肺癌的疗效分析

目的:评价MVP(MMC VDS PDD)、NP(Vinorelbine PDD)、TP(Paclitaxel PDD)三种化疗方案治疗晚期非小细胞肺癌的疗效.方法:114例晚期非小细胞肺癌患者分为3组,MVP组36例,MMC(丝裂霉素)8mg/m2,静脉推注,d1;Vindesine(长春地辛)3mg/m2,静脉点滴,d1,8;PDD(顺铂)80mg/m2,静脉点滴,d3.NP组4l例,Vinorelbine(长春瑞宾)25mg/m2,静脉点滴,d1,8,PDD 80mg/m2,静脉点滴,d3.TP组37例,Paclitaxel(紫杉醇)175mg/m2,静脉点滴,d1,PDD 80mg/m2,静脉点滴,d3.每4周为1周期,至少2周期.结果:MVP、NP及TP的有效率分别为33.2%、34.1%、40.5%;中位生存期分别为8.2个月、7.1个月、9.1个月;1年生存率分别为30.5%、34.1%、37.8%.主要不良反应MVP组为骨髓抑制及恶心、呕吐;NP组为骨髓抑制、恶心、呕吐及静脉炎;TP组为骨髓抑制、恶心、呕吐、肌肉关节疼痛及脱发.结论:MVP、NP及TP化疗方案在治疗晚期非小细胞肺癌的有效率、中位生存期及1年生存率相似,毒性可耐受.     

A phase II study of single-agent oral vinorelbine in patients with pretreated advanced non-small-cell lung cancer

PURPOSE: Intravenous vinorelbine has demonstrated its efficacy and tolerability in advanced non-small-cell lung cancer (NSCLC). An oral formulation of vinorelbine has been developed, and a number of phase II studies have shown its activity in chemotherapy-naive NSCLC, even in elderly patients, but no study has been performed to test activity and toxicity of oral vinorelbine in pretreated patients. The aims of our study were to investigate the activity and toxicity of oral vinorelbine in patients with NSCLC as salvage treatment. PATIENTS AND METHODS: Twenty pretreated patients with locally advanced (n = 6) and metastatic (n = 14) NSCLC entered the study. The schedule was oral vinorelbine 60 mg/m(2) once a week until progression or development of unacceptable toxicity. Median age was 70 years (range, 49-84 years). RESULTS: Seventeen patients were evaluable for response and all for toxicity. A median of 9 cycles were administered (range, 2-21 cycles). No objective responses were reported, 5 patients experienced stable disease, and 12 patients had progressive disease. Median time to progression was 2 months (range, 1-6 months), and median survival was 4 months (range, 1-13 months). Treatment was well tolerated, with grade 4 neutropenia in 1 patient (heavily pretreated); grade 2 diarrhea in 2 patients; asthenia in 2 patients; and abdominal pain in 1 patient. CONCLUSION: Oral vinorelbine 60 mg/m(2) once a week is a very safe schedule in heavily pretreated locally advanced and metastatic NSCLC; however, at this dose, the drug is inactive. Other phase II studies with oral vinorelbine 80 mg/m(2) weekly are warranted.     

Phase II study of vinorelbine/ifosfamide/cisplatin for the treatment of advanced non-small-cell lung cancer

PURPOSE:: to evaluate the combination of vinorelbine, ifosfamide and cisplatin(VIP) in patients with advanced nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS:: Seventy-six untreated patients with stages IIIB-IV NSCLC; thechemotherapy regimen consisted of vinorelbine (25 mg/sqm ondays 1 and 8), ifosfamide (3 g/sqm on day 1 with uroprotectivemesna), and cisplatin (80 mg/sqm on day 1). The cycles wereadministered on an out patient basis every 3 weeks. RESULTS:: Leukopenia was the most frequent toxicity: grades 3–4neutropenia was observed in 26% of the cycles and 19 episodesof febrile neutropenia were reported in 289 evaluable courses.Filgrastim 5 µg/kg was administered in 27% of the courses.Sixty-seven of 76 patients were evaluable for response: theoverall response rate was 51% (95% confidence interval 35%–%)with 2 complete responses (3%) and 32 (48%) partial responses.No significant differences in response rate were observed accordingto histology or stage of disease. The median time to progressionwas 6 months (range 1 to 29+) and the median overall survival10 months (range 1–33+). CONCLUSION:: The combination of vinorelbine, ifosfamide and cisplatin inthe dose and schedule employed in this trial shows an interestingresponse rate with acceptable toxicities. This regimen shouldbe tested in the multimodality therapy of stage IIIA/B NSCLC. vinorelbine, ifosfamide, cisplatin, non-small-cell, lung cancer     

S-1 plus cisplatin combination chemotherapy in patients with advanced non-small cell lung cancer: a multi-institutional phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non-small-cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m(2) twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. This schedule was repeated every 5 weeks. RESULTS: Of 56 patients enrolled in the study, 55 patients were eligible and analyzed. The median number of cycles administered was 3 (range, 1-12 cycles). Among these 55 patients, one complete response and 25 partial responses were observed with an overall response rate of 47% (95% confidence interval, 34-61%). The median survival time was 11 months and the 1-year survival rate was 45%. Hematologic toxicities of grades 3 and 4 included neutropenia (29%) and anemia (22%). No grade 4 nonhematologic toxicity was observed. Grade 3 toxicity included anorexia (13%), vomiting (7%), or diarrhea (7%). CONCLUSIONS: S-1 plus cisplatin combination chemotherapy showed a promising effectiveness with acceptable toxicity rates in patients with advanced NSCLC. These results warrant further investigations of this regimen including a randomized controlled trial for its use as a first line treatment for NSCLC.     

Toxicity of FED chemotherapy in non-small-cell lung cancer

Twenty-eight patients with metastatic and/or recurrent non-small-cell lung cancer were treated with a new sequential combination of escalating doses of cisplatin (50, 75, and 100 mg/m2 IV X 1) followed by 5-FU infusion (40 mg/m2/hour X 72) and etoposide (80 mg/m2/day X 3). Three patients received concurrent external radiation therapy. Eleven of the 28 (39%) had a partial response to chemotherapy. Four others had a minor response. One partial responder became a complete responder by surgical excision of residual cancer. Median time to response was 6 weeks followed by a median response duration of 4 months. In responders, chemotherapy was discontinued at the time of maximal response. Median survival was 7 months. Chemotherapy was well tolerated with absence of leucopenia, thrombocytopenia, and nausea and vomiting in a majority of courses. The common toxicities were alopecia (100%), leucopenia (35%), nausea and vomiting (30%), and electrolyte imbalances (27%). Reversible nephrotoxicity, thrombocytopenia, anemia, mucositis, and diarrhea were infrequent. The response rate in stage IV was less than in stage III. The combination of moderate doses of cisplatin, 5-FU infusion, and etoposide provides a new palliative chemotherapy that is well tolerated with concurrent/sequential radiation therapy and may be useful in the multimodality treatment of non-small-cell lung cancer.     

Vinorelbine plus low-dose cisplatinum with concomitant radiotherapy for the treatment of locally advanced or inoperable non-metastasized non-small-cell lung cancer (stage I-IIIB): a phase II study.

In a phase II study, we assessed the toxicity and efficacy of daily low-dose cisplatin (6 mg/m2) and weekly vinorelbine (15 mg/m2) with concurrent thoracic irradiation (60 Gy) for locally advanced non-metastasized non-small-cell lung cancer. The overall response rate was 65%, complete response 12% and the median overall survival was 64 weeks.     

Unfavorable therapeutic index of cisplatin/gemcitabine/vinorelbine in advanced non-small-cell lung cancer

In view of favorable reports with the 3-drug combination of PGV (cisplatin/gemcitabine/vinorelbine), this multicenter phase II study evaluated the therapeutic index of PGV in patients with advanced non-small-cell lung cancer (NSCLC). Thirty-two patients with stage IV NSCLC and 1 with stage IIIB were studied. There were 23 men and 10 women, with a median age of 63 years (range, 38-80 years). Twelve patients had a performance status (PS) of 0, and 21 patients had a PS of 1. Treatment consisted of cisplatin 50 mg/m2, gemcitabine 1000 mg/m2, and vinorelbine 25 mg/m2 all given intravenously on days 1 and 8, in 21-day cycles. Fifteen patients (45%; 95% confidence interval (CI), 28%-64%) achieved a partial response. Median response duration was 3 months (range, 1-9 months). The median and 1-year survival rates were 9.4 months and 39% (95% CI, 23%-58%), respectively. The median number of cycles was 4. Only 3 patients (9%) completed treatment without regimen modifications. Median dose intensity (% planned) was cisplatin 24 mg/m2/week (72%), gemcitabine 483 mg/m2/week (72%), and vinorelbine 12 mg/m2/week (72%). Toxicities were predominantly hematologic, with grade 3/4 neutropenia (67%), febrile neutropenia (21%), and thrombocytopenia (67%). There were 3 (9%) treatment-related deaths due to neutropenic complications. This study confirms the substantial antineoplastic activity of PGV. We observed a high rate of severe hematologic toxicity, especially febrile neutropenia, despite a lower delivered dose intensity of PGV. Given these results, PGV appears to offer no therapeutic advantage to current doublet regimens.     

Phase II trial of oral vinorelbine in combination with cisplatin followed by consolidation therapy with oral vinorelbine in advanced NSCLC

BACKGROUND: Among the cytotoxic agents commonly combined with cisplatin in the treatment of advanced NSCLC, vinorelbine has led to significant outcome improvements. Adding more than four cycles of the combination regimen increase toxicities. The availability of an oral form of vinorelbine appeared as a particularly convenient way to provide a consolidation treatment to patients who have achieved an objective response or stable disease. PATIENTS AND METHODS: This multi-centre phase II open-label, non-comparative study was designed to evaluate the treatment with four cycles of the combination chemotherapy with oral vinorelbine at the dose of 60 mg/m2 on day 1 and day 8 for the first cycle and then 80 mg/m2 plus cisplatin 80 mg/m2 on day 1 every 3 weeks followed for patients with objective response or stable disease by consolidation therapy with oral vinorelbine at 80 mg/m2 weekly on patients with unresectable localised or metastatic non-small-cell lung cancer (NSCLC). The primary endpoint was tumor response. The secondary objectives were progression free-survival, overall survival and toxicity assessment. Visual analogue scales (VAS) filled by the patients were also used to evaluate subjective changes under treatment, reflecting patients' clinical benefit. RESULTS: Fifty-six patients enrolled into the study from April 2001 to April 2002 received the combination regimen. Twenty-five patients (43.9%) also received the subsequent consolidation treatment. Partial tumor responses were obtained in 13 patients (26.5%, 95% CI 15.0-41.1) of 49 evaluable patients. Stable disease was observed in 22 (44.9%) of patients. The median duration of response was 6 months (95% CI 4.3-8.2). The median progression free-survival was 4.2 months (95% CI 2.8-6). The median overall survival time was 10 months (95% CI 7.4-14) and the 1 year survival was 42.6%. The main toxicities recorded were haematological. Grade 3 and 4 neutropenia were observed in 16 patients (29.1%). Nausea, vomiting and fatigue were the major non-haematological toxicities reported. Among the symptoms recorded by the patients on VAS scales (appetite, fatigue, pain, cough, dyspnea, haemoptysis), except anorexia, all symptoms were improved during the combination therapy and in the consolidation phase. CONCLUSION: This study confirms that the efficacy of the cisplatin/oral vinorelbine combination in NSCLC is comparable to cisplatin/I.V. vinorelbine. This study also suggests that consolidation therapy with vinorelbine alone may probably prolong the efficacy of the combination regimen. The convenience offered to patients by an oral form of vinorelbine is a definite asset for consolidation therapy.     

Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer

OBJECTIVE: Paclitaxel-cisplatin is considered to be a standard therapy for metastatic non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the activity and toxicity of this combination with vinorelbine or gemcitabine as front-line therapy in brain metastases from NSCLC. METHODS: Twenty-six chemotherapy-naive patients with an ECOG performance status of 0-2 were treated with paclitaxel (135 mg/m(2)) on day 1, cisplatin (120 mg/m(2)) on day 1, and either vinorelbine (30 mg/m(2)) on days 1 and 15 or gemcitabine (800 mg/m(2)) on days 1 and 8. Whole-brain irradiation was offered early in case of progression and later as consolidation treatment. RESULTS: All patients were evaluated for toxicity and 25 for response. An intracranial response rate was observed in 38% of the patients (95% CI: 22-59%). WHO grade 3-4 neutropenia and thrombocytopenia occurred in 31 and 4% of the patients, respectively. There was one treatment-related death. Non-hematological toxicities were mild. After a median follow-up of 46 months, the median overall survival for all patients was 21.4 weeks and the median time to progression was 12.8 weeks. CONCLUSIONS: Paclitaxel and cisplatin combined with vinorelbine or gemcitabine as front-line therapy in brain metastases seem to achieve responses similar to those for extracranial disease, suggesting a meaningful role in this setting.     

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.     

Oral vinorelbine in combination with cisplatin: a novel active regimen in advanced non-small-cell lung cancer.

BACKGROUND: A phase II trial of alternating i.v. and oral vinorelbine in combination with cisplatin was designed to determine the response rate, safety profile, progression-free survival, overall survival and quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-six chemotherapy-na?ve patients received cisplatin 100 mg/m(2) and i.v. vinorelbine 25 mg/m(2) on day 1, followed by oral vinorelbine 60 mg/m(2) on days 8, 15 and 22, every 28 days. RESULTS: After an independent review, the response rate was 33% [95% confidence interval (CI) 20% to 46%]. Median progression-free and overall survival were 5.5 months (95% CI 3.7-6.4) and 8.9 months (95% CI 8.8-11.7), respectively. The most frequent hematological toxicities were neutropenia (grade 3-4 in 73% of patients) and anemia (grade 3-4 in 11% of patients). Grade 3-4 infections and non-hematological toxicities occurred occasionally. QoL for lung cancer related symptoms was stable or improved. CONCLUSIONS: The efficacy and safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15 and 22) in combination with cisplatin in advanced NSCLC are similar to those of the standard regimen using exclusively i.v. vinorelbine, whereas ease of administration and patient comfort may favor the novel approach.     

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。     

口服长春瑞滨联合顺铂与静滴长春瑞滨联合顺铂治疗局部晚期或转移的非小细胞肺癌的Ⅱ期临床研究

目的:评价口服长春瑞滨联合顺铂和静滴长春瑞滨联合顺铂治疗局部晚期或转移的非小细胞肺癌（NSCLC ）的疗效，分析两组患者的无进展生存期、毒性反应以及治疗的安全性。方法:符合入组标准的患者按1:1 比例随机分配到口服长春瑞滨联合顺铂的试验组和静滴长春瑞滨联合顺铂的对照组。两组均接受每3 周一次的化疗方案。第一疗程中口服长春瑞滨按60mg/m2，d1、d8，静滴长春瑞滨按25mg/m2，d1、d8，顺铂均按80mg/m2，d1。若第一疗程中未出现严重的血液学毒性，第二疗程开始口服长春瑞滨的剂量增加至80mg/m2，静滴长春瑞滨的剂量增至30mg/m2。按RECIST标准评价肿瘤缓解情况，按NCI-CTC 2.0 版本评价毒
性分级。结果:中山大学肿瘤防治中心共入组39例合格受试者，试验组19例，对照组20例，两组受试者在性别、年龄、KPS 评分、临床分期、组织学类型及吸烟状况是均衡的。采用意向性人群分析方法。试验组和对照组的客观缓解率分别为31.6% 和42.1%（P=0.737），临床获益率分别为52.6% 和68.4%（P=0.508），中位无进展生存期分别为85天和115 天（P=0.705）。 两组主要的毒性反应均为中性粒细胞减少症、贫血、胃肠道反应、静脉炎。对照组2 级静脉炎发生率明显高于试验组（68.4% vs 21.1%），差异有统计学意义（P=0.008）。 其他的不良反应和Ⅲ～Ⅳ度的不良反应两组受试者未观察到有统计学差异。结论:口服长春瑞滨联合顺铂与静滴长春瑞滨联合顺铂的方案在治疗晚期非小细胞肺癌的疗效相似，毒副作用减轻，值得开展更大规模Ⅲ期临床研究进一步评价口服长春瑞滨在亚洲人群中的疗效和毒性。      

长春瑞滨联合顺铂治疗晚期非小细胞肺癌160例近期疗效

 目的　观察长春瑞滨 (NVB)和顺铂 (DDP)联合治疗晚期非小细胞肺癌 (NSCLC)的临床疗效及毒副作用。方法　 160例Ⅲb～Ⅳ期初次治疗的非小细胞肺癌 ,用NVB联合DDP(NP方案 )治疗 :NVB2 5mg/m2 ,静滴d1,8,DDP 80mg/m2 静滴d1。结果　有效率 (CR +PR) 55.6% ,中位缓解期 6.2个月。中位生存期 12 .2个月。主要毒副反应为骨髓抑制。结论　NP方案治疗晚期非小细胞肺癌疗效高 ,副反应少 ,病人可耐受 ,值得临床作为一线治疗推广     

Paclitaxel, cisplatin, and vinorelbine combination chemotherapy in metastatic non-small-cell lung cancer

Vinorelbine-cisplatin combination chemotherapy is a standard approach for the treatment of advanced non-small-cell lung cancer (NSCLC). The addition of paclitaxel as a third therapeutic agent seems promising. The aim of the present study was to evaluate the activity and toxicity of this new regimen. Forty-six nonselected and chemotherapy-naive patients with stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 2 were treated every 4 weeks with paclitaxel (135 mg/m2 given iv in 3 hours) and cisplatin (120 mg/m2 given iv in 6 hours) on day 1 and vinorelbine (30 mg/m2 given iv in 30 minutes) on days 1 and 15. All patients were evaluated for toxicity and response according to the intent-to-treat principle. An objective response was observed in 39% of the patients (95% CI: 25% to 55%). World Health Organization grade III to IV neutropenia, thrombocytopenia, and anemia occurred in 43%, 2%, and 17%, respectively. There was one treatment-related death. Nonhematologic toxicities were mild, mainly grade III nausea and vomiting in 20% of the patients. After a median follow-up period of 54 months, the median progression-free survival was 14.3 weeks and the median overall survival was 31.3 weeks. This three-drug chemotherapy combination is feasible, well tolerated, and shows activity in metastatic NSCLC.     

奥沙利铂加长春瑞滨与顺铂加长春瑞滨治疗晚期非小细胞肺癌的随机对照研究

目的探索奥沙利铂＋长春瑞滨（NL方案）与顺铂＋长春瑞滨（NP方案）治疗晚期非小细胞肺癌（NSCLC）的疗效、不良反应及患者的生活质量。方法可评价疗效的NSCLC患者以2：1比例随机分入治疗组与对照组。治疗组70例,化疗方案为长春瑞滨25mg／m^2静脉冲入,第1。8天;奥沙利铂130mg／m^2静脉滴注,第2天;21d为1个周期。对照组32例,化疗方案为顺铂80mg／m^2静脉滴注,分2—3d给予;长春瑞滨用法同治疗组。结果治疗组与对照组的有效率分别为35．7％和43．8％（P=0．4）,中位肿瘤进展时间分别为4．7个月和5．5个月（P=0．6）,1年生存率分别为38．5％和58．6％（P=0．07）。治疗组Ⅰ-Ⅱ度感觉异常发生率为68．4％,显著高于对照组的36．4％（P：0．0017）;而治疗组I一Ⅱ度粒细胞减少率为49．4％,显著低于对照组的70．6％（P：0．037）。两组患者各项生活质量评分差异无统计学意义。结论奥沙利铂＋长春瑞滨治疗晚期NSCLC疗效确切,患者耐受性良好,为晚期NSCLC的治疗提供了一种新的选择。