NP方案与TP方案治疗晚期非小细胞肺癌临床分析

目的评价NP方案、TP方案治疗晚期非小细胞肺癌的疗效和毒副反应.方法 NP方案:长春瑞滨(NVB) 25 mg/m2,快速静脉滴注,第1、8天;顺铂(PDD)45 mg/m2,静脉点滴,第1～2天.TP方案:紫杉醇(PTX)135 mg/m2,静脉点滴,第1天,持续3 h;PDD 80 mg/m2,静脉点滴,第2天.21 d为一周期.结果 NP组30例,CR 2例(6.7%),PR 12例(40.0%),SD 12例(40.0%),总有效率46.7%;TP组29例,CR 1例(3.4%),PR 12例(41.4%),SD 11例(37.9%),总有效率44.8%.NP组和TP组中位缓解时间分别为5.5个月和4.5个月.初治优于复治(NP组为72.7%对31.6%,P=0.0308;TP组为75.0%对33.3%,P=0.0480);Ⅲb期优于Ⅳ期(NP组为77.8%对33.3%,P=0.0288;TP组为85.7%对31.8%,P=0.0176).剂量限制性毒性主要为骨髓抑制,NP组较TP组稍重,白细胞、血小板减少发生率分别为66.7%、51.7%和33.3%、31.0%.TP组脱发、周围神经毒性/疼痛较NP组重,而NP组静脉炎及胃肠道反应较TP组重.无Ⅳ度反应出现,患者均能够较好地耐受,不影响化疗继续进行.结论 NP方案、TP方案治疗晚期非小细胞肺癌安全有效,既可用作一线方案,也可用作二线方案,且二者无明显交叉耐药性,可互为挽救方案.     

Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan.

BACKGROUND: To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan (IP) in patients with untreated advanced non-small-cell lung cancer (NSCLC) by a non-inferiority design. PATIENTS AND METHODS: A total of 602 patients were randomly assigned to one of four regimens: cisplatin 80 mg/m(2) on day 1 plus irinotecan 60 mg/m(2) on days 1, 8, 15 every 4 weeks (IP) carboplatin AUC 6.0 min x mg/mL (area under the concentration-time curve) on day 1 plus paclitaxel 200 mg/m(2) on day 1 every 3 weeks (TC); cisplatin 80 mg/m(2) on day 1 plus gemcitabine 1000 mg/m(2) on days 1, 8 every 3 weeks (GP); and cisplatin 80 mg/m(2) on day 1 plus vinorelbine 25 mg/m(2) on days 1, 8 every 3 weeks (NP). RESULTS: The response rate, median survival time, and 1-year survival rate were 31.0%, 13.9 months, 59.2%, respectively, in IP; 32.4%, 12.3 months, 51.0% in TC; 30.1%, 14.0 months, 59.6% in GP; and 33.1%, 11.4 months, 48.3% in NP. No statistically significant differences were found in response rate or overall survival, but the non-inferiority of none of the experimental regimens could be confirmed. All the four regimens were well tolerated. CONCLUSION: The four regimens have similar efficacy and different toxicity profiles, and they can be used to treat advanced NSCLC patients.     

紫杉醇联合顺铂及长春瑞滨联合卡铂治疗老年晚期非小细胞肺癌的临床对照研究

为了探讨紫杉醇联合顺铂及长春瑞滨联合卡铂方案对老年晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)的疗效和毒副反应,选取初治晚期NSCLC65例,分别应用TP(紫杉醇 顺铂)、NE(长春瑞滨 卡铂)方案治疗。每例均完成2个周期化疗后评价疗效及毒副反应。结果两组患者近期有效率TP组为41·9%(13/31),NE组为41·2%(14/34),差异无统计学意义,P>0·05。中位生存期TP组8·1个月,NE组7·2个月,差异无统计学意义,P>0·05。两组毒副反应均以骨髓抑制、脱发及恶心呕吐为主,TP组恶心呕吐发生率为87·1%,NE组为73·5%,白细胞减少TP组为74·9%,NE组为85·3%。两组病例均无化疗相关死亡发生。初步研究结果提示,TP、NE联合方案是治疗老年晚期NSCLC有效且耐受性较好的方案。     

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。     

Bavituximab plus paclitaxel and carboplatin for the treatment of advanced non-small-cell lung cancer

Objective

Bavituximab is a phosphatidylserine (PS)-targeting monoclonal antibody with immune-modulating and tumor-specific vascular targeting properties. Preclinical studies have shown activity against numerous solid tumors and at least an additive effect in combination with chemotherapy. This study evaluated bavituximab in combination with paclitaxel and carboplatin in patients with previously untreated, locally advanced or metastatic non-small-cell lung cancer (NSCLC).

Patients and methods

This phase II, open-label study (NCT00687817) was conducted in 49 patients with stage IIIB/IV NSCLC utilizing a Simon two-stage design. Patients were treated with up to six cycles of carboplatin area under the concentration–time curve (AUC) 5 plus paclitaxel 175 mg/m² every 21 days with weekly bavituximab 3 mg/kg followed by bavituximab monotherapy until progression or unacceptable toxicity.

Results

The primary efficacy endpoint of overall response rate (ORR) was 40.8% (complete response [CR] 2.0%, partial response [PR] was 38.8%). Median progression-free survival (PFS) and overall survival (OS) were 6.0 and 12.4 months, respectively. Treatment-related adverse events (AEs) occurred in 40.8% of patients. The most common treatment-related AEs were anemia (10.2%), asthenia, vomiting, paresthesia, anorexia, and fatigue (6.1% each). One patient with a central, cavitating squamous tumor developed fatal hemoptysis and aspiration.

Conclusion

Bavituximab in combination with paclitaxel–carboplatin as first-line therapy demonstrated a tolerable safety profile and potential efficacy in this single-arm phase II trial in patients with advanced local or metastatic NSCLC. Randomized trials with this regimen are in progress.

ClinicalTrials.gov identifier

NCT00687817.     

Cost-effectivenes of paclitaxel plus cisplatin in advanced non-small-cell lung cancer.

The aim of this study was to assess the cost-effectiveness of combination chemotherapy with paclitaxel/cisplatin, compared with standard etoposide/cisplatin in patients with advanced non-small cell lung cancer (NSCLC). We obtained the primary survival and resource utilization data from a large three-arm randomized trial comparing: paclitaxel 135 mg m(-2) by 24-h intravenous (i.v.) infusion + cisplatin; paclitaxel 250 mg m(-2) by 24-h i.v. infusion + cisplatin + granulocyte colony-stimulating factor (G-CSF); and standard etoposide/cisplatin in patients with stage IIIb or IV NSCLC. We also modelled the regimens with paclitaxel 135 mg m(-2) + cisplatin administered as an outpatient by 3-h infusion, as clinical data suggest that this is equivalent to 24-h infusion. We collected costing data from the Ottawa Regional Cancer Centre and applied it to the resources consumed in the randomized trial. We integrated these data into the Statistics Canada POpulation HEalth Model (POHEM), which generated hypothetical cohorts of patients treated with each regimen. The POHEM model assigned diagnostic work-up, treatment, disease progression and survival characteristics to each individual in these cohorts and tabulated the costs associated with each. We did sensitivity analyses around the costs of chemotherapy and its administration, and the survival differences between the two regimens. All costs are in 1997 Canadian dollars ($1.00 Canadian approximately Pound 0.39 sterling). The perspective is that of the Canadian health care system. In the trial, the two paclitaxel-containing arms had almost identical survival curves with a median survival of 9.7 months compared with 7.4 months for etoposide/cisplatin. As administered in the trial, paclitaxel/cisplatin cost $76,370 per life-year gained (LYG) and paclitaxel/cisplatin/G-CSF $138,578 per LYG relative to etoposide/cisplatin. However, when modelled as an outpatient 3-h infusion, paclitaxel/cisplatin was moderately cost-effective at $30,619 per LYG. When compared with historical controls treated with best supportive care, this regimen of paclitaxel/cisplatin cost $4539 per LYG. Assuming a 3-h paclitaxel infusion yields the same survival advantage as the 24-h infusion did in the randomized trial, paclitaxel/cisplatin is a cost-effective improvement over standard etoposide/cisplatin for patients with advanced non-small cell lung cancer.     

长春瑞宾联合顺铂或顺铂/丝裂霉素一线治疗不可手术非小细胞肺癌

目的比较长春瑞宾联合顺铂和丝裂霉素(MNP)和长春瑞宾联合顺铂(NP)一线治疗晚期非小细胞肺癌(NSCLC)的疗效与安全性.方法65例经细胞学或病理确诊的NSCLC患者分别接受MNP或NP方案化疗.长春瑞宾25 mg/m2静注,d18 c;顺铂为75 mg/m2,静脉滴注d1;MNP方案中丝裂霉素用法为6 mg/m2,静注第1天.两方案均每3周重复,两周期后评价疗效,并随访毒副反应.结果两组中位化疗周期数均为3.NP组PR为11例,总体有效率为33%;PD 5例(15%);MNP组PR为12例(38%),PD为5例(16%),与NP组相比,差异无显著性(P＞0.05).常见副反应有白细胞减少、贫血、便秘、恶心、呕吐等.MNP组Ⅲ与Ⅳ度白细胞减少症发生率高达41%;有3例因中性粒细胞减少并发感染而发热,其中1例死亡.NP与MNP组中位生存期分别为12与11个月,差异无统计学意义.结论长春瑞宾联合顺铂和丝裂霉素一线治疗晚期NSCLC在疗效上不优于长春瑞宾联合顺铂,毒副反应增加;不应作为晚期NSCLC的常规一线方案.     

长春瑞滨联合顺铂治疗非小细胞肺癌

目的：观察长春瑞滨（诺维本,ＮＶＢ）联合顺铂（ＤＤＰ）治疗非小细胞肺癌的疗效。方法：６０例患者分别用ＮＰ（ＮＶＢ加ＤＤＰ）方案和ＭＮＰ「丝裂霉素（ＭＭＣ）联合ＮＶＢ与ＤＤＰ」方案治疗。结果：ＮＰ和ＭＮＰ组有效率分别为４２．９％（１２／２８）和４６．９％（１５／３２）,两者无显著差异（Ｐ〉０．０５）。分析诸多因素对疗效的影响发现,病期早较病期晚疗效好,鳞癌比腺癌疗效好。骨髓抑制为限制性毒性,白细胞下     

Phase II randomized trial of vinorelbine and gemcitabine versus carboplatin and paclitaxel in advanced non-small-cell lung cancer.

BACKGROUND: The purpose of this study was to compare quality of life and overall toxicity in patients with advanced non-small-cell lung cancer (NSCLC) treated with vinorelbine-gemcitabine (VG) or carboplatin-paclitaxel (Taxol) (CP). PATIENTS AND METHODS: A total of 165 previously untreated patients were randomized to the two regimens. Quality of life was assessed by the Lung Cancer Symptom Scale (LCSS). Overall toxicity and secondary efficacy end points were evaluated by standard WHO criteria. RESULTS: There was no significant difference in overall quality of life between the two treatments. Neutropenia, thrombocytopenia, peripheral neuropathy, and alopecia, were more common in the CP arm, whereas constipation was more frequent in the VG arm. Response rates were 14.6% in the VG arm and 16.9% in the CP arm. Median survival times were 7.8 and 8.6 months, and 1 year survival rates were 38.4% and 31.9%, respectively. CONCLUSIONS: Patients treated with VG experienced lower toxicity, but overall quality of life was similar in both arms. Efficacy seemed comparable between VG and CP. Our study shows that VG is a viable alternative to platinum-based chemotherapy in patients with advanced NSCLC.     

吉西他滨联合顺铂或卡铂治疗晚期非小细胞肺癌的近期疗效

目的 :观察吉西他滨 (gemcitabine)联合顺铂与吉西他滨联合卡铂治疗晚期非小细胞肺癌的疗效和毒性反应。方法 :10 6例经病理组织学或细胞学证实的晚期非小细胞肺癌患者分为GP和GC两组 ,GP组应用吉西他滨 10 0 0mg/m2 ,静滴 ,第 1、8天 ;顺铂 30mg/m2 ,静滴 ,第 1～ 3天。GC组应用吉西他滨 10 0 0mg/m2 ,静滴 ,第 1、8天 ;卡铂ACU =5 ,静滴 ,第 1天。 2 1天为 1个周期 ,连用 2个周期评价疗效。结果 :GP组和GC组有效率 (CR PR)分别为 4 8.1%和 4 4 .2 % (P >0 .0 5 ) ;中位疾病进展时间分别为 6 .8个月和 6 .2个月 (P >0 .0 5 ) ;毒性反应中GP组消化道毒副反应较GC组大 ,差异有显著性 ;骨髓毒性两组相当 ,差异无显著性。结论 :吉西他滨联合顺铂及吉西他滨联合卡铂两方案治疗晚期非小细胞肺癌疗效均较好 ,毒性反应轻微 ,患者耐受良好 ,尤其吉西他滨联合卡铂的消化道反应轻 ,患者易于接受 ,值得临床进一步研究。     

长春瑞滨加卡铂或顺铂治疗晚期非小细胞肺癌的比较

目的 :观察比较长春瑞滨加卡铂与长春瑞滨加顺铂治疗晚期非小细胞肺癌的疗效及不良反应。方法 :178例晚期非小细胞肺癌患者分别接受长春瑞滨加卡铂 (NC)与长春瑞滨加顺铂 (NP)方案治疗 ,两组患者一般特征具有可比性 (P >0 0 5 )。结果 :NC组及NP组有效率分别为 4 3 7% ( 38/ 87)及 4 5 1% ( 4 1/ 91)。NC组中位生存期 11个月 ,1年生存率37 9% ,3年生存率 9 2 % ;NP组中位生存期 10个月 ,1年生存率 38 5 % ,3年生存率 9 9% ,两组疗效差异无显著性 (P >0 0 5 )。骨髓抑制为两种方案剂量限制性毒性 ,NC及NP组Ⅲ～Ⅳ度白细胞减少发生率分别是 2 2 3%及 2 1 1% (P >0 0 5 )。NP组消化道反应较NC组明显 ( 36 5 % ,7 9% ) (P >0 0 5 ) ,其他不良反应发生率两组接近 ,所有不良反应均能耐受。结论 :NC及NP方案均为治疗晚期NSCLC有效安全的方案 ,两方案疗效相当 ,不良反应接近 ,NC方案消化道反应更为轻微。     

Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial.

PURPOSE: We conducted this randomized study comparing the activity and toxicity of paclitaxel and gemcitabine (PG) and paclitaxel and carboplatin (PC) combinations for the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to paclitaxel 200 mg/m(2) on day 1 plus either carboplatin at an area under the concentration-time curve of 6 on day 1 (group A) or gemcitabine 1,000 mg/m(2) on days 1 and 8 (group B) every 3 weeks. A retrospective cost analysis was conducted using Student's t test to compare independent samples between groups. RESULTS: A total of 509 patients (group A, 252 patients; group B, 257 patients) were enrolled; all characteristics were well balanced. The median survival time was 10.4 months (95% confidence interval [CI], 8.8 to 12 months) for group A and 9.8 months (95% CI, 8.0 to 11.7 months) for group B (P =.32). Respective 1-year survival rates were 41.7% and 41.4%. The response rate for group A was 28.0% (2% complete response [CR], 26% partial response [PR] [95% CI, 22% to 34%]), and the response rate for group B was 35.0% (5% CR, 30% PR) [95% CI, 29% to 41%]) (P =.12). Toxicity was mild. Grades 3/4 neutropenia, thrombocytopenia, and anemia for groups A and B were seen in 15% and 15%, 2% and 1%, and 5% and 2%, respectively. The mean total cost (outpatient clinic visits plus chemotherapy drug fee) for group A (euro; 7,612.64) versus group B (euro; 7,484.77) was not statistically significant (P <.66). CONCLUSION: The PG combination is as equally active and well tolerated as the PC combination in patients with advanced NSCLC.     

Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer.

PURPOSE: To evaluate whether the addition of gemcitabine (G) to vinorelbine (V) improves survival and quality of life (QoL) among elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with NSCLC aged >/= 70 years with advanced disease were randomly allocated to receive V 30 mg/m(2) on days 1 and 8 every 3 weeks or G 1,200 mg/m(2) + V 30 mg/m(2) on days 1 and 8 every 3 weeks. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned based on the first 60 patients per arm. RESULTS: In May 1999, the survival data were analyzed of 120 eligible patients (V group = 60; G + V group = 60) who had been randomized from June 1997 to February 1999. Forty-nine patients had stage IIIB disease, and 71 had stage IV. At a median potential follow-up of 14 months (range, 3 to 22 months), 93 patients had died (G + V group = 41; V group = 52). In the G + V group, median survival time was 29 weeks and projected 1-year survival was 30%; these values were 18 weeks and 13% in the V group. According to multivariate Cox analysis, the risk of death in the G + V arm compared with the V arm was 0.48 (95% confidence interval, 0. 29 to 0.79; P <.01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The overall response rates were 22% and 15% in the G + V and V groups, respectively. CONCLUSION: In elderly patients with NSCLC, G + V treatment is associated with significantly better survival than is V alone.     

Carboplatin plus gemcitabine therapy versus carboplatin plus weekly paclitaxel therapy for advanced non-small cell lung cancer

We compared two chemotherapy regimens for advanced non small-cell lung cancer. The CG regimen consisted of carboplatin (AUC 4 to 5) on day 1 plus gemcitabine (1,000 mg/m(2)) on day 1 and 8, every three weeks, while the CP regimen was carboplatin (AUC 6) on day 1 plus paclitaxel (70 mg/m(2)) on day 1, 8 and 15, every four weeks. There was a total of 62 patients, 23 on the CG regimen and 39 on the CP regimen. In initial treatment, the response rate, time to progression and median survival time in the CG regimen and CP regimens were 40% vs 22%, 124 days vs 67 days, and 422 days vs 328 days, respectively. There was no statistical difference in the outcome. However, the toxicity profile was different in the two regimens. Grade 3/4 neutropenia and thrombocytopenia were frequent in the CG regimen (61% vs 31%, p=0.02, 44% vs 3%, p=0.0002, respectively). Non hematological toxicity including grade 2 alopecia was less in the CG regimen (4% vs 36%, p=0.012). In choosing the chemotherapeutic regimen for non small cell cancer, it is important to consider the toxicity.     

Phase II study of paclitaxel and carboplatin for advanced non-small-cell lung cancer

A prospective phase II study was conducted to determine the response, toxicity and survival rate of lung cancer patients treated with combination paclitaxel and carboplatin in stage IIIB and IV NSCLC. Eligible patients required measurable and/or evaluable diseases; performance status (ECOG) 0-2; no previous chemotherapy; adequate hepatic, renal and bone marrow function. Paclitaxel was administered at a dose of 200 mg/m2, 3 h infusion, followed by carboplatin at an AUC of 6. Treatment was repeated every 3 weeks for six courses. G-CSF 5 microgram/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leucopenia or granulocytopenia in the previous course. From April 1996 through July 1997, 53 patients were enrolled; all are assessable for toxicity and response. The median age was 56 years (range, 20-77 years). Sixty four percent were male, 64% had adenocarcinoma and 62% had stage IV disease. Two hundred and seventy two courses were administered; 36 patients (68%) completed all six cycles. Two patients achieved a complete response (4%) and 27 patients achieved a partial response (51%), for an overall response rate of 55%. Sixteen patients had stable disease (30%) and 8 patients had progressive disease (15%). The median progression free survival time for all patients, stage IIIB and stage IV patients was 28 weeks (range, 18-37 weeks), 31 weeks (range 21-41 weeks) and 22 weeks (range 16-29 weeks), respectively. The median survival time and 1 year survival rate for all patients was 55 weeks (range, 51-59 weeks) and 55%, respectively. Stage IIIB patients had better median survival time and 1-year survival rate than stage IV patients (75 vs. 46 weeks, P = 0.007; 80% vs. 42%, P = 0.003). Grade 3 and 4 granulocytopenia, anemia and thrombocytopenia were observed in 25, 3, and 1%, respectively, of the 272 courses administered. G-CSF was required in 28% of the 272 courses. There were four episodes of febrile neutropenia (1.5%), three episodes of angina pectoris (1%) and one episode of anaphylaxis (0.4%). Other common toxicities, generally mild, included myalgia, arthralgia, peripheral neuropathy and asthenia. Most toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.     

A phase II study of paclitaxel plus cisplatin for advanced non-small-cell lung cancer in Japanese patients

We performed a clinical phase II trial of the combination of paclitaxel and cisplatin in patients with locally advanced (stage IIIB) or metastatic non-small-cell lung cancer (NSCLC) using a 3-h infusion of paclitaxel followed by a 1 to 2-h infusion of cisplatin, with a short premedication regimen. Treatment was repeated every 21 days for at least two cycles. The patients received paclitaxel 180 mg/m2 followed by cisplatin 80 mg/m2. Enrolled in the trial were 33 chemotherapy-naive patients with stage IIIB (15%) or stage IV (85%) NSCLC. Their median age was 61 years (range 43-71 years). Of the 33 patients, 10 (30%) were women and 23 (70%) were men, and 82% had adenocarcinoma. With 78 courses of chemotherapy administered, 32 patients were evaluable for toxicity and response. Hematologic toxicities were moderate: Japan Clinical Oncology Group (JCOG) grade 3 or 4 neutropenia occurred in 37% of the cycles (53% of patients). Other toxicities consisted mainly of grade 1 or 2 alopecia and nausea/vomiting, but also included grade 1 or 2 neuropathy (47%), hypotension (grade 1 in 6%, grade 3 in 3%) and allergic reactions (grade 1 or 2 in 16%, grade 3 in 3%). Of 32 patients evaluable for response, a partial response was achieved in 10 (31%; 95% confidence interval 16% to 50%), stable disease was seen in 16 (50%), and disease progression was seen in 2 (6%). The median survival time was 14.8 months and the 1-year survival rate was 56%. These results suggest that the combination of paclitaxel and cisplatin is a well-tolerated and active regimen in Japanese patients with advanced NSCLC. In view of the promising survival outcomes, further evaluation in prospective randomized trials with other regimens is warranted.