长春瑞滨联合奥沙利铂治疗晚期非小细胞肺癌的临床研究

目的：观察长春瑞滨（NVB）联合奥沙利铂（LOHP）治疗晚期非小细胞肺癌的临床疗效及不良反应。方法：将经病理组织学或细胞学确诊为非小细胞肺癌的患者作为研究对象，60剜患者随机分为治疗组和对照组，各30例。治疗组给予NVB加LOHP治疗，21天为一周期，用2周期；对照组给予NVB加DDP（顺铂）治疗，21天为一周期，用2周期。结果：总有效率治疗组为43．3％，对照组为40．0％（P〉0．05）。不良反应以白细胞减少、恶心、呕吐以及周围神经炎为主，Ⅲ～Ⅳ度的恶心、呕吐、肾功能损害及心功能不全主要发生在对照组，周围神经炎主要发生在治疗组（P〈0．05）。结论：长春瑞滨联合奥沙利铂治疗晚期非小细胞肺癌的近期疗效与长春瑞宾联合顺铂治疗的疗效相似，均有较好的疗效。但长春瑞滨联合奥沙利铂组的不良反应比长春瑞滨联合顺铂组轻，病人更容易耐受，可以作为晚期非小细胞肺癌的一线治疗方案，更适宜老年患者及心肺功能不全的患者。     

长春瑞滨联合顺铂治疗非小细胞肺癌40例疗效观察

目的 观察长春瑞滨（NVB）联合顺铂（DDP）治疗非小细胞肺癌的疗效与毒性。方法 对40例非小细胞肺癌（NSCLC）患者采用长春瑞滨联合顺铂治疗：NVB 25mg/m^2,静脉点滴，第1、8天；DDP 30mg/m^2,静脉点滴，第1、3天。结果 有效率（CR＋PR）为40％。腺癌有效率为35％；鳞癌有效率为42％。2组有效率比较无显著性差异（P＞0．05）。初治者的有效率为44％，复治者的有效率为33％，2组有效率比较无显著性差异（P＞0．05）。不良反应：WBC下降Ⅲ度52％、Ⅳ度为18％；PLT下降Ⅲ度5％、Ⅳ度为18％，其他不良反应较轻微。结论 NP方案治疗NSCLC疗效较好，不良反应可以耐受。     

长春瑞滨联合铂类治疗中晚期子宫内膜癌

目的：比较长春瑞滨和紫杉醇分别与铂类联合治疗中晚期子宫内膜癌的近期疗效及毒副反应。方法：33例晚期子宫内膜癌，治疗组（NP方案组）21例，长春瑞滨＋顺铂或卡铂化疗，长春瑞滨25mg／m^2，静注d1、8；顺铂25mg／m^2，静注d1～3，或卡铂（300mg／m^2或者AUC4～5）静脉滴注d1。对照组（TP方案组）12例：紫杉醇135～150mg／m^2，静注d1；顺铂或卡铂用法同前。结果：全组均完成2周期以上化疗，其中CR4例．PR14例，NC10例，PD5例。有效率（CR＋PR）54．54％。NP方案组，CR2例，PR9例，有效率（CR＋PR）52．38％；TP方案组，CR2例，PR5例，有效率（CR＋PR）58．33％，两组间无统计学差异（P〉0．05）。副反应主要为骨髓抑制、白细胞、血小板减少，Ⅲ～Ⅳ度发生率，NP组为71．43％，TP组为75．0％（P〉0．05）。结论：长春瑞滨＋铂类联合与紫杉醇＋铂类联合化疗治疗中晚期子宫内膜癌有相同的疗效且毒副反应可以耐受。     

国产长春瑞滨联合顺铂治疗晚期乳腺癌的临床观察

目的观察国产长春瑞滨（商品名：盖诺）联合顺铂方案治疗晚期乳腺癌的临床疗效及毒性反应．方法运用国产长春瑞滨25mg／m2，d1，d8加顺铂25mg／m^2，d1-3治疗晚期乳腺癌52例．结果总有效率达48．1％，CR2例，PR23例。主要不良反应为骨髓抑制，胃肠道反应和静脉炎。白细胞减少的发生率76．9％，其中Ⅲ～Ⅳ度达36．5％；恶心、呕吐的发生率67.3％，多为Ⅰ～Ⅱ；静脉炎的发生率11．5％．结论国产长春瑞滨联合顺铂对中晚期乳腺癌疗效确切，且毒性可以耐受，可以作为晚期乳腺癌病人的二线治疗方案。     

肺癌联合化疗中顺铂或奥沙利铂两组疗效对照研究

目的：观察多西紫杉醇联合顺铂与多西紫杉醇联合奥沙利铂治疗晚期非小细胞肺癌（NSCLC）的近期疗效和毒副作用。方法：118例不能手术或术后复发转移的Ⅲ期-Ⅳ期NSCLC患者随机分组，接受多西紫杉醇联合顺铂或多西紫杉醇联合奥沙利铂方案，化疗2周期-3周期后评价疗效。结果：多西紫杉醇联合顺铂组有效率为49．9％，部分缓解率为44．8％；多西紫杉醇联合奥沙利铂组有效率为48．3％，部分缓解率为45．0％，两组近期疗效比较无统计学意义（P〉0．05）。多西紫杉醇联合顺铂组Ⅲ＋Ⅳ度白细胞下降21例（36．2％），而多西紫杉醇联合奥沙利铂组9例（15％），（P〈0．05）；Ⅲ＋Ⅳ度消化道反应在多西紫杉醇联合顺铂组为12例（20．7％），多西紫杉醇联合奥沙利铂组仅4例（6．7％），（P〈0．05）。多西紫杉醇联合顺铂组发生神经毒性6例（10．3％），多西紫杉醇联合奥沙利铂组55例（91．7％），（P〈0．05）。结论：多西紫杉醇联合顺铂或奥沙利铂是治疗晚期非小细胞肺癌（NSCLC）较有效的方案。     

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。     

紫杉醇与长春瑞滨联合顺铂治疗晚期非小细胞肺癌

目的比较紫杉醇（T）及长春瑞滨（N）联合顺铂（P）治疗Ⅲb／Ⅳ期非小细胞肺癌（NSCLC）的疗效、毒副反应。方法对晚期非小细胞肺癌48例，分别应用TP和NP方案化疗，治疗2周期评价疗效和毒副反应。结果44例可评价疗效，两组近期有效率分别为45．0％和46．8％，无显著性差异（x^2=2．25，P=0．512）。两组间主要毒性反应为消化道反应和骨髓抑制，其Ⅲ、Ⅳ度反应发生率无统计学差异（P〈0．05），TP组过敏性休克2例，心衰2例，但对症处理后均恢复，无死亡病例。NP组无过敏性休克和心脏毒性反应。结论两方案的近期疗效和血液毒性及消化道毒性反应相近，但应用紫杉醇时应注意过敏性休克和心衰的发生，一旦发生，如及时对症处理，一般无严重后果。两方案均为目前非小细胞肺癌较好的治疗方案。     

长春瑞滨联合顺铂方案治疗晚期非小细胞肺癌

目的 研究长春瑞宾(NVB)联合顺铂(DDP)方案(NP方案)治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副作用方法：91例经病理或细胞学诊断非小细胞肺癌患者，其中腺癌56例，鳞癌27例，肺泡细胞癌4例．大细胞肺癌3例；细胞学涂片为癌细胞1例。初治80例，复治11例；Ⅲ期32例(Ⅲa期2例，Ⅲb期30例)．Ⅳ期59例，采用长春瑞滨(NVB)25mg/m^2，第1、8天静滴；顺铂(DDP)90～loomg/m^2静滴，21天为1个周期结果：部分缓解(PR)37例，稳定(SD)30例，进展(PD)24例，总有效率为40．6％(95％CI：30．5％～50．7％)：中位进展期5月(95％CI：4～6月)，中位生存期13月(95％，CI：11～15月)，一年生存率52.7％(95％CI：42.4％～62．9％)。WHOⅢ Ⅳ度白细胞下降占40．7％，为主要血液毒性结论：长春瑞滨联合顺铂治疗晚期’NSCLC疗效确切，毒副反应性可耐受，价格适中，为符合国情的治疗晚期非小细胞肺癌的方案。     

长春瑞滨联合顺铂治疗晚期非小细胞肺癌

目的：观察长春瑞滨联合顺铂治疗晚期非小细胞肺癌的疗效和毒副反应。方法：对经病理组织学或细胞学证实的46例晚期非小细胞肺癌患者，给予长春瑞滨与顺铂联合治疗，其中长春瑞滨25mg/m^2、静脉滴注，第1、8天给药；顺铂90mg/m^2，静脉滴注，分为第1～3天给药。21天为一周期，每位患者治疗3周期。结果：全组完全缓解2例，部分缓解19例，稳定21例，进展4例，总有效率为45．6％。最常见的毒副反应为骨髓抑制，Ⅲ度～Ⅳ度白细胞、白血板减少率分别为47．8％和8．7％，其余毒性反应均轻微可耐受。结论：长春瑞滨联合顺铂治疗晚期非小细胞肺癌疗效较好，毒性可以耐受。     

紫杉醇、顺铂方案与长春瑞滨、顺铂方案治疗晚期非小细胞肺癌疗效比较

目的 观察紫杉醇（TAX）、顺铂（DDP）组成的TP方案与长春瑞滨（NVB）、顺铂（DDP）组成的NP方案治疗晚期非小细胞肺癌（NSCLC）的疗效和毒副反应。方法 102例Ⅲ—Ⅳ期NSCLC病人随机分为TP方案组48例：TAX135—150mg／m^2，d1；DDP25mg／m^2，d1-3；NP方案组54例：NVB40mg／次，d1、d8，DDP25mg／m^2，d1-3。结果 TP方案组有效率52．1％，中位缓解期5．4个月；NP方案组有效率53．7％，中位缓解期5．0个月。两组近期疗效及中位缓解期比较均无显著性差异（P〉0．05）。两组主要毒副反应为骨髓抑制、恶心呕吐、脱发及关节肌肉疼痛在TP方案组明显，静脉炎在NP方案组多见，两组比较有显著性差异（P〈0．05）。结论 TP方案和NP方案是治疗晚期NSCLC较有效的方案。两组疗效相似，毒副反应均可耐受。     

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.     

Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer.

BACKGROUND: The Lung Cancer Cetuximab Study is an open-label, randomized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone, in patients with advanced EGFR-expressing, non-small-cell lung cancer (NSCLC). End points of the study are activity, safety and pharmacokinetics. PATIENTS AND METHODS: Following randomization, for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m(2), day 1) and vinorelbine (25 mg/m(2) on days 1 and 8) alone or following cetuximab treatment (initial dose 400 mg/m(2), followed by 250 mg/m(2) weekly thereafter). RESULTS: Eighty-six patients were randomly allocated to the study (43 per arm). Confirmed response rates were 28% in the cisplatin/vinorelbine arm (A) and 35% in the cetuximab plus cisplatin/vinorelbine arm (B). Median progression-free survival (PFS) was 4.6 months in arm A and 5.0 months in arm B, with PFS rates at 12 months of 0% and 15%, respectively. Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0% and 16%, respectively. The cetuximab combination was well tolerated. CONCLUSION: In the first-line treatment of advanced NSCLC, the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone.     

Long term analysis of survival in the European randomized trial comparing vinorelbine/cisplatin to vindesine/cisplatin and vinorelbine alone in advanced non-small cell lung cancer

In the period 1989-1991, 612 patients with inoperable stage IIIA/B and IV non-small cell lung cancer (NSCLC) were randomized in a phase III trial comparing three chemotherapy regimens. Survival data at five and six years of follow-up confirm the overall benefit of treatment with a combination of vinorelbine and cisplatin compared to vindesine plus cisplatin or vinorelbine alone. Of the 612 patients randomized at the start of the study, 17 have survived beyond five years. Of these patients, eight had entered the trial with metastatic disease. Multivariate analysis to detect prognostic factors suggested a possible interaction between the effect of having cisplatin in the chemotherapy received and baseline performance status. Subgroup analysis subsequently confirmed that the survival benefit of the vinorelbine plus chemotherapy regimen is evident only in patients with initial World Health Organization performance status (PS) of 0-1. Among these patients, the one-year survival rate is 38% for the vinorelbine/cisplatin arm, 29% for vindesine/cisplatin and 34% for vinorelbine alone. The corresponding figures for median survival are 43, 33 and 36 weeks. Among inoperable NSCLC patients with a PS of 2, who appear from this trial not to have benefited from the presence of cisplatin in their chemotherapy, use of single agent vinorelbine is an appropriate treatment option.     

Epirubicin/vinorelbine as first line therapy in metastatic breast cancer

This study was aimed at investigating the toxicity and activity of the combination epirubicin and vinorelbine in chemotherapy-naive patients with metastatic breast cancer. Fifty-one patients with measurable or evaluable metastatic breast cancer entered the study. The regimen consisted of epirubicin 90 mg/m² as a slow i.v. infusion on day 1, followed by vinorelbine 25 mg/m² by 30-minute intravenous infusion on days 1 and 8; the courses were repeated every 21 days for a maximum of 8 cycles. All the patients were assessable for toxicity and 47 were evaluable for response according to the World Health Organization (WHO) criteria.Objective responses were observed in 33 out of 47 evaluable patients (70.2%; 95% C.I. 55.1%–82.6%) with 4 complete (8.5%) and 29 partial responses (61.7%); 11 patients had stable disease (23.4%) and 3 patients progressed while on treatment. The median time to progression was 10 months (range 1 – 21) and the median overall survival was 23 months (range 2 – 32+). Neutropenia was the most frequent toxicity: a grade 4 neutropenia (WHO) was reported in 70% of 252 courses with a median duration of 3 days (range 1–6). Seventeen episodes of febrile neutropenia were observed but only 1 patient required hospital admission. Other hematologic toxicities were negligible. One patient experienced a paralytic ileus requiring hospitalization; no peripheral neuropathy such as muscle weakness or paresthesia was observed. No treatment-related cardiotoxicity was reported. The encouraging response rate achieved with epirubicin/vinorelbine, the easily manageable toxicities of the combination, and its feasibility in an outpatient setting make this combination worthy of further comparative trials with standard regimens.     

A multicenter prospective phase II randomized trial of epirubicin/vinorelbine versus pegylated liposomal doxorubicin/vinorelbine as first-line treatment in advanced breast cancer. A GOIM study

Background

To evaluate activity and tolerability of two anthracycline-containing regimens as first-line treatment for anthracycline-naïve relapsed breast cancer patients.

Methods

Patients with relapsed breast cancer not previously treated with adjuvant anthracyclines were randomly assigned to epirubicin/vinorelbine (arm A: EPI/VNB, EPI 90 mg/m² on day 1, VNB 25 mg/m² on days 1,5 plus G-CSF subcutaneously on days 7-12, with cycles repeated every 21 days), or to pegylated liposomal doxorubicin/VNB (arm B: PLD/VNB, PLD 40 mg/m² on day 1, VNB 30 mg/m² on days 1, 15, with cycles repeated every 4 weeks). Primary objective was to evaluate the efficacy of the two regimens in terms of response rate, secondarily toxicity, progression free survival and overall survival.

Results

One hundred and four patients have been enrolled (arm A 54, arm B 50): characteristics were well balanced between the 2 arms. Responses were as follows: arm A, 3 (5.6%) CR, 20 (37%) PR, (ORR 42.6%, 95%CI 29.3%-55.9%); arm B, 8 (16%) CR, 18 (36%) PR, (ORR 52%, 95%CI 38.2%-65.8%). Median progression free survival was 10.7 months in arm A (95% CI, 8.7-12.6), and 8.8 months in arm B (95% CI, 7.1-10.5). Median overall survival was 34.6 months in arm A (95%CI, 19.5-49.8) and 24.8 months in arm B (95%CI, 15.7-33.9). As toxicity concerns, both treatment regimens were well tolerated; myelosuppression was the dose-limiting toxicity, with G3-4 neutropenia occurring in 18.5% and 22% of the patients of arm A and B, respectively. No relevant differences in main toxic effects have been observed between the two arms, except for alopecia, more common in arm A, and cutaneous toxicity, observed only in arm B. No clinical congestive heart failures have been observed, one case of tachyarrhythmia was reported after the last EPI/VNB cycle, and two reversible ≥ 20% LVEF decreases have been observed in arm A.

Conclusions

Both anthracycline- containing regimens evaluated in the present study seem to be active and with a satisfactory tolerability in anthracycline-naïve relapsed breast cancer patients.     

Phase I/II study of paclitaxel and vinorelbine in metastatic breast cancer

Paclitaxel and vinorelbine are among the most active new agents in metastatic breast cancer. Both in vitro and in vivo studies have shown that the combined administration of these two microtubule-targeting agents is feasible and worthwhile. Based on the promising preclinical data, patients with metastatic breast cancer no longer amenable to conventional treatment were entered into a phase I/II study in which the vinorelbine dose was fixed at 30 mg/sqm and paclitaxel was started at 90 mg/sqm and then subsequently escalated by 30 mg/sqm per step. Cycles were repeated every 21 days. Hematopoietic growth factor support was provided from the 4th dose level onwards. Grade III neutropenia was observed only in 2 patients treated at the 5th dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occured in all three patients treated at the 6th dose level. Other toxicities were mild. Paclitaxel 210 mg/sqm and vinorelbine 30 mg/sqm was the selected combination for phase II. Overall response rate in 34 evaluable patients was 38% (95% confidence interval (C.I.), 22% to 54%). In particular, 3 complete responses (9%) and 10 partial responses (29%) were observed. The observed level of antitumor activity, with an overall response rate of 38% and a median duration of response of 12 months, is of interest, since the study was targeted only to anthracycline-pretreated patients, most of whom had adverse prognostic features. The evaluation of a combination of vinorelbine and paclitaxel as first-line therapy in metastatic breast cancer seems worthwhile and is currently undergoing.     

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     

A case of recurrent lung cancer successfully treated with vinorelbine and cisplatin/carboplatin

A 73-year-old male underwent lobectomy with ND2a lymph node dissection and resection of the superior vena cava for right lung cancer in December 1998 at Akita University Hospital. Histopathological examination demonstrated moderately differentiated adenocarcinoma (pT4 (SVC) N2M0, Stage IIIB). He received 1 course of a combination of cisplatin (CDDP) and etoposide (ETP) as postoperative adjuvant therapy. In March 2001, he again underwent partial resection of the right lung (S8) due to recurrence. In December 2001, a new left lung metastatic tumor was found. The patient was transferred to our hospital, where he was given 1 course of vinorelbine (NVB) 25 mg/m2 (day 1, 8) and CDDP 80 mg/m2 (day 1). Subsequently, he received 2 courses of vinorelbine (NVB) 25 mg/m2 (day 1, 8) and carboplatin (CBDCA) 430 mg/body (day 1). After the chemotherapy, a complete response (CR) of metastatic lesions was achieved. Adverse reactions were grade 3 neutropenia, grade 2 alopecia and grade 1 nausea/vomiting. The combination of vinorelbine and platinum agent (CDDP/CBDCA) is a useful regimen in treating recurrent non-small-cell lung cancer.     

Schedule-dependent synergism of vinorelbine and 5-fluorouracil/UFT against non-small cell lung cancer

Elderly patients with advanced non-small cell lung cancer (NSCLC) require chemotherapy that is effective and minimally toxic. We evaluated the activity of a combination of vinorelbine and 5-fluorouracil (5-FU)/UFT (a fixed combination of tegafur and uracil) in vitro and in vivo to establish a rationale for clinical use. The cytotoxic activities of various combinations of vinorelbine and 5-FU, the active metabolite of tegafur, were analyzed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazlium bromide (MTT) assay and isobologram technique in vitro, using 3 NSCLC cell lines (A549, PC14, and Ma10). Sequential exposure to vinorelbine followed by 5-FU showed additive or synergistic activity against all 3 NSCLC cell lines tested. The reverse sequence showed no synergism. Antitumor activity and survival prolongation after treatment with different combinations of vinorelbine and UFT were evaluated in nude mice bearing PC14 xenografts. Treatment with vinorelbine before UFT was associated with higher antitumor activity, less toxicity, and longer survival than the reverse sequence. To clarify the underlying mechanism by which the combination exerts the synergistic effects, the expression of thymidylate synthase (TS) was assessed by Western blot analysis in vitro and by immunohistochemical analysis in an animal model. Vinorelbine suppressed the 5-FU-induced increase in TS protein in A549 cells. In PC14 tumor tissues of animal models, TS expression in cancer cells was suppressed by vinorelbine. Our data suggest that treatment with vinorelbine injection before oral UFT may have synergistic activity against NSCLC. This synergistic activity may be attributed to increased chemosensitivity to UFT caused by vinorelbine-induced suppression of TS.