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。     

Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group.

PURPOSE: To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC) compared with vinorelbine plus cisplatin as first-line chemotherapy. PATIENTS AND METHODS: Patients (n = 1,218) with stage IIIB to IV NSCLC were randomly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks (DCb); or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks (VC). RESULTS: Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients (P =.044; hazard ratio, 1.183 [97.2% confidence interval, 0.989 to 1.416]). The 2-year survival rate was 21% for DC-treated patients and 14% for VC-treated patients. Overall response rate was 31.6% for DC-treated patients v 24.5% for VC-treated patients (P =.029). Median survival (9.4 v 9.9 months [for VC]; P =.657; hazard ratio, 1.048 [97.2 confidence interval, 0.877 to 1.253]) and response (23.9%) with DCb were similar to those results for VC. Neutropenia, thrombocytopenia, infection, and febrile neutropenia were similar with all three regimens. Grade 3 to 4 anemia, nausea, and vomiting were more common (P <.01) with VC than with DC or DCb. Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients, who experienced deterioration in QoL. CONCLUSION: DC resulted in a more favorable overall response and survival rate than VC. Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC. These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC.     

Interim analysis of a phase III trial comparing cisplatin, gemcitabine, and vinorelbine vs. either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non small-cell lung cancer. A Southern Italy Cooperative Oncology Group Study

In a previous phase II randomized study, a cisplatin/gemcitabine/vinorelbine (PGV) regimen produced a 50-week median survival time (MST) in advanced non small-cell lung cancer (NSCLC) patients. The present trial was planned to randomly compare the outcome of patients treated with this new triplet regimen with those of patients receiving either cisplatin plus vinorelbine (PV) or cisplatin plus gemcitabine (PG) doublet combinations. One hundred eighty patients with stage IIIB (76) or IV (104) disease, aged 相似文献   

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。     

Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial

PURPOSE: This randomized, multicenter, phase III trial was conducted to compare the tolerability of gemcitabine plus cisplatin (GP) vs. gemcitabine plus carboplatin (GC) in chemonaive patients with stage IIIb and IV non-small cell lung carcinoma (NSCLC). Secondary objectives were to evaluate response, duration of response, time to progressive disease (TTPD), and survival. PATIENTS AND METHODS: Eligible patients were required to have stage IIIb or IV NSCLC, no previous chemotherapy, Karnofsky performance status of at least 70, bidimensionally measurable disease, and age 18-75 years. Randomized patients in both arms were given gemcitabine 1200 mg/m(2) on days 1 and 8, followed on day 1 by cisplatin 80 mg/m(2) (GP) or carboplatin AUC=5 (GC). Treatment cycles were repeated every 21 days for a maximum of six cycles, or until disease progression or unacceptable toxicity occurred. RESULTS: Enrolled patients in both arms, 87 in GP and 89 in GC, were well balanced for demographics and disease characteristics. Dose intensity was 93.8 and 92.7% for gemcitabine in GP/GC arms, respectively; 97.7% for cisplatin and 99.9% for carboplatin. Patients with at least one grade 3/4 toxicity excluding nausea, vomiting or alopecia, were 44% in GP arm and 54% in GC arm. The only significantly different toxicities were, nausea and vomiting in GP and thrombocytopenia in GC group. The overall response rates, median TTPD, response duration and survival were, 41/29%, 5.87/4.75 months, 7.48/5.15 months, and 8.75/7.97 months for GP and GC arms, respectively. CONCLUSION: GP and GC are effective and feasible regimens for advanced NSCLC, and are comparable in efficacy and toxicity. GC may offer acceptable option to patients with advanced NSCLC, especially those who are unable to receive cisplatin.     

Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project.

PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non-small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 100 mg/m(2) on day 2, every 28 days, or mitomycin 6 mg/m(2), ifosfamide 3,000 mg/m(2), and mesna on day 1 plus cisplatin 100 mg/m(2) on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P =.029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P =.877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P <.001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P <. 001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.     

A randomized phase II trial of sequential gemcitabine plus vinorelbine followed by gemcitabine plus ifosfamide versus gemcitabine plus cisplatin in the treatment of chemo-naive patients with stages III and IV non-small cell lung cancer (NSCLC)

BACKGROUND: Third-generation platinum-based combinations are established as first-line treatment for advanced non-small cell lung cancer (NSCLC). Non-platinum regimens could be an alternative if they show similar efficacy with better tolerability. This randomized phase II trial compared the objective tumor response rate (ORR) of sequential gemcitabine plus vinorelbine followed by gemcitabine plus ifosfamide versus gemcitabine plus cisplatin. Secondary objectives included time to disease progression (TTP), overall survival and toxicity. METHODS: Chemo-naive patients with stages III and IV NSCLC and Karnofsky performance status >70 were assigned to receive either (a) gemcitabine 1000mg/m(2) plus vinorelbine 25mg/m(2) on days 1 and 8 for 2 cycles, followed by gemcitabine 1000mg/m(2) on days 1 and 8 plus ifosfamide 2000mg/m(2) on day 1 (GV-GI arm) for 2 cycles or (b) gemcitabine 1250mg/m(2) on days 1 and 8 with cisplatin 70mg/m(2) on day 1 (GC arm) for 4 cycles. RESULTS: Between July 2001 and January 2003, 102 patients were enrolled (50 on the GV-GI arm and 52 on the GC arm). Patient characteristics were balanced between arms (GV-GI arm: median age 59 years, 84% male, 22 stage IIIB, 24 stage IV, 4 stage IIIA; GC arm: median age 56 years, 87% male, 27 stage IIIB, 23 stage IV, 2 stage IIIA). Of the 101 patients evaluable for response, ORR was significantly higher on the GC arm than on the GV-GI arm (25% versus 6%, respectively; p=0.007). No complete responses occurred. TTP was longer on the GC arm than on the GV-GI arm (median 135 and 79 days, respectively), although this difference was not statistically significant (p=0.065). Survival was not significantly different between the arms (median 293 and 197 days, respectively; p=0.16). Although significantly more thrombocytopenia was reported on the GC arm (22% and 4%, respectively; p=0.02), it did not lead to more transfusions (15 transfusions in 5 patients versus 14 transfusions in 6 patients, respectively). There was no significant difference in other safety parameters between treatment arms. CONCLUSIONS: GC appears to produce better response in advanced NSCLC than GV-GI, with a trend towards longer TTP. Except for more thrombocytopenia with GC, similar toxicity profiles were observed.     

GN方案与NP方案一线治疗晚期非小细胞肺癌56例

 目的　比较分析并探讨长春瑞滨（NVB）联合吉西他滨（GEM）的GN方案与NVB联合顺铂（DDP）的NP方案治疗晚期非小细胞肺癌（NSCLC）的疗效及患者不良反应。方法　回顾性分析经组织学证实的56例晚期NSCLC患者，GN组27例：NVB＋GEM，每3周 1个周期×2～6个周期，NP组29例：NVB＋DDP，每3周1个周期×2～6个周期。结果　GN组总有效率37.0 %，肿瘤控制率59.3 ％，中位疾病进展期5.1个月，1年生存率40.7 %，其疗效与NP组接近，差异无统计学意义（P >0.05），但GN组在血红蛋白下降、Ⅱ度以上恶心、呕吐及体力下降三项不良反应方面发生率明显低于NP组，两组之间不良反应统计差异有统计学意义（P＜0.05）。结论　非铂类GN方案疗效高、毒性低、耐受性好，作为晚期NSCLC患者的一线替代方案值得进一步研究。     

泽菲联合盖诺治疗不能耐受顺铂的中晚期非小细胞肺癌临床观察

目的评价泽菲联合盖诺治疗不能耐受顺铂的中晚期非小细胞肺癌的疗效和毒性反应。方法74例中晚期非小细胞肺癌既往均未曾放疗或化疗。PS评分≤3分,生存期超过3个月,随机分为GN组25例（泽菲联合盖诺）,NP组24例（盖诺加顺铂）,GP组25例（泽菲加顺铂）。结果GN组、NP组和GP组有效率分别为44.0%、37.5%和44.0%,差异无显著性（P〉0.05）。GN组与另两组在Ⅲ、Ⅳ度血液学毒性方面比较差异无显著性（P〉0.05）,GN组非血液学毒性比较少（P〈0.05）。结论GN方案疗效较好且毒性较低,故尤其适合于不能耐受顺铂的晚期非小细胞肺癌患者。     

A randomized phase II study of vinorelbine plus gemcitabine with/without cisplatin against inoperable non-small-cell lung cancer previously untreated

Phase II studies have suggested that vinorelbine (V) plus gemcitabine (G) treatment has a similar response rate and better toxicity profile than cisplatin-based combination chemotherapy in non-small-cell lung cancer (NSCLC). Our aim was to evaluate whether or not the addition of cisplatin (P) to a VG regimen increases the efficacy or toxicities in chemo-naive inoperable NSCLC patients. From April 2002 to October 2003, 86 patients were enrolled. The treatment dose was V 20 mg/m2 plus G 800 mg/m2 intravenous infusion (i.v.) on days 1, 8 and 15, with/without P 60 mg/m2 i.v. on day 15, every 4 weeks. The efficacy and toxicity of the treatment were recorded. In all, 125 cycles of VG and 178 cycles of VGP were given to the patients in the VG and VGP arms, respectively (P = 0.001). The median cycle of treatment was three in the VG arm and five in the VGP arm. There were 10 partial responses (overall 23.3%) in the VG arm and 1 complete response and 19 partial responses (overall 46.5%) in the VGP arm (P = 0.022). Neutropenia, nausea, vomiting, and peripheral neuropathy were more common in the VGP arm (P = 0.023, 0.002, 0.025, 0.001, respectively). The Lung Cancer Symptom Scale showed no difference between the VG and VGP arms after two cycles of treatment or when the patient went off study. We concluded that the addition of P to VG treatment did increase both the tumor response rate and the toxicities. However, the toxicities were tolerable.     

Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group.

PURPOSE: In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non-small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG). PATIENTS AND METHODS: From April 1997, patients with locally advanced or metastatic NSCLC, an age of < or = 70 years, and an Eastern Cooperative Oncology Group performance status < or = 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m(2), gemcitabine 1,000 mg/m(2), and vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m(2) on days 1 and 29 and vinorelbine 30 mg/m(2)/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival. RESULTS: The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P <.01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen. CONCLUSION: The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.     

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.     

Economic analysis of vinorelbine plus cisplatin versus paclitaxel plus carboplatin for advanced non-small-cell lung cancer

BACKGROUND: It is increasingly important to have timely information about the economic impact of new cancer therapies in today's cost-conscious environment. Nearly 170 000 people are diagnosed with lung cancer annually in the United States. We performed an economic analysis alongside Southwest Oncology Group Trial S9509 to estimate the cost-effectiveness of cisplatin plus vinorelbine versus carboplatin plus paclitaxel for patients with advanced non-small-cell lung cancer. There were no statistically significant differences in survival or cancer-related quality of life between the treatment arms. METHODS: Use of both protocol and nonprotocol lung cancer-related health care was tracked for 24 months from the initiation of therapy. To determine expenditures, nationally standardized costs were applied to each type of health care service used, and these were summed over time. Lifetime expenditures and 95% confidence intervals (CIs) for each arm of the trial were calculated with the use of a multivariate regression technique that accounts for censoring. Student's t tests were used to compare the difference in costs between the arms. All statistical tests were two-sided. RESULTS: Cancer-related health care costs over the period of observation averaged 40,292 dollars (95% CI = 36,226 dollars to 44,359 dollars) for patients in the cisplatin plus vinorelbine arm versus 48,940 dollars (95% CI = 44,674 dollars to 53,208 dollars) for patients in the carboplatin plus paclitaxel arm (P =.004), with a mean difference of 8648 dollars (95% CI = 2634 dollars to 14,662 dollars). Protocol chemotherapy drugs and medical procedures costs were statistically significantly higher in the paclitaxel arm (P =.0003 and P<.0001, respectively), whereas protocol chemotherapy delivery costs were statistically significantly higher in the vinorelbine arm (P<.0001). There was no difference between the arms in costs for blood products, supportive care medications, nonprotocol-related inpatient or outpatient care, and nonprotocol chemotherapy. CONCLUSIONS: Treatment with carboplatin plus paclitaxel is substantially and statistically significantly more expensive than treatment with cisplatin plus vinorelbine. The majority of the cost difference is due to the additional cost of the protocol chemotherapy (approximately 12,000 dollars). Notable differences in costs of downstream health care were not apparent.     

Randomized phase III study of gemcitabine and vinorelbine versus gemcitabine, vinorelbine, and cisplatin in the treatment of advanced non-small-cell lung cancer: from the German and Swiss Lung Cancer Study Group.

PURPOSE: To evaluate whether cisplatin-based chemotherapy (gemcitabine, vinorelbine, and cisplatin [GVP]) prolongs overall survival in comparison to cisplatin-free chemotherapy (gemcitabine and vinorelbine [GV]) as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between September 1999 and June 2001, 300 patients with NSCLC stage IIIB with malignant pleural effusion or stage IV disease were randomly assigned to receive GV (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks) or GVP (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 + cisplatin 75 mg/m(2) on day 2 every 3 weeks). Primary end point of the study was overall survival. RESULTS: Two hundred eighty-seven patients (GV, 143 patients; GVP, 144 patients) were eligible for analysis. At the time of analysis, April 15, 2002, 209 patients (GV, 103 patients; GVP, 106 patients) of 287 patients had died (73%). No statistically significant difference was observed for overall survival (P =.73; median survival, 35.9 versus 32.4 weeks; 1-year survival rate, 33.6% versus 27.5%) as well as for event-free survival (P =.35; median time-to-event, 19.3 versus 22.3 weeks) between GV and GVP. Two hundred fourteen patients were assessable for best response. The overall response rates were 13.0% for GV versus 28.3% for GVP (P =.004; complete responders, 0% versus 3.8%; partial responders, 13.0% versus 24.5%). Hematologic and nonhematologic toxicity was significantly lower in the GV treatment arm compared with GVP. No statistically significant difference in quality of life was observed. CONCLUSION: In this phase III study, the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen, which was substantially better tolerated.     

Gemcitabine and cisplatin versus vinorelbine and cisplatin versus ifosfamide+gemcitabine followed by vinorelbine and cisplatin versus vinorelbine and cisplatin followed by ifosfamide and gemcitabine in stage IIIB-IV non small cell lung carcinoma: a prospective randomized phase III trial of the Gruppo Oncologico Italia Meridionale

PURPOSE: we carried out a phase III randomized trial to compare vinorelbine-cisplatin regimen to gemcitabine-cisplatin regimen, and to a sequential administration of gemcitabine-ifosfamide followed by vinorelbine-cisplatin or the opposite sequence of vinorelbine-cisplatin followed by ifosfamide-gemcitabine according to the 'worst drug rule' hypothesis in patients with locally advanced unresectable stage IIIB or metastatic stage IV non-small cell lung cancer. The primary endpoint was survival parameters, while secondary endpoints included analysis of response rates and toxicity. PATIENTS AND METHODS: patients were randomized to receive: (a) gemcitabine 1000 mg/m(2) on days 1, 8 and 15 plus ifosfamide 1500 mg/m(2) on days 8-12 with mesna uroprotection (GI regimen) followed by vinorelbine 25 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 1 (GI --> VC regimen); (b) the opposite sequence (VC --> GI); (c) vinorelbine plus cisplatin as above described (VC regimen); or (d) gemcitabine 1400 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 8 (GC regimen). All regimens were given every 4 weeks. All patients were chemotherapy naive and had a ECOG PS 0-2. RESULTS: 400 patients were enrolled into the trial. Interim analysis after inclusion of 243 patients showed that ORR were 19% in the GI --> VC arm, 32% in the inverse sequence arm (CV --> GI), 42% in the VC arm, and 30% in the GC arm. The VC arm was statistically superior over the GI --> VC arm (p = 0.0074), but not over the other regimens. Median TTP was 3.1 months in the GI --> VC arm versus 5.0 months in the VC --> GI arm (p = 0.014). For these reasons the GI --> VC and VC --> GI arm were closed since the 'worst drug rule' hypothesis was rejected. Accrual in the VC and GC arms continued up to 140 and 138 patients respectively. Final ORR were 44% for the VC regimen (4 CR), and 34% for the GC regimen (1 CR). This difference was statistically significant (p = 0.032). OS was 9.0 and 8.2 months, respectively, with no statistically significant difference. The 1-year survival rate was 24 and 20%, respectively for VC and GC regimens. As expected the incidence of phlebitis was higher in the VC arm, while thrombocytopenia, flu-like syndrome and asthenia were more frequent in the GC arm. CONCLUSIONS: the results of this trial indicate that the combination of vinorelbine and cisplatin and that of gemcitabine and cisplatin are equivalent in terms of median TTP and OS, although the vinorelbine-cisplatin regimen is associated with a higher ORR. Both regimens may be considered as reference treatments for future studies. Moreover, our data reject the 'worst drug rule' hypothesis of sequential treatments in NSCCL at least with the combination used in this study.     

Gemcitabine, vinorelbine and cisplatin combination chemotherapy in advanced non-small cell lung cancer: a phase II trial

The purpose of this phase II trial was to investigate the efficacy and safety of a combination chemotherapy with gemcitabine, vinorelbine and cisplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Patients with NSCLC stage IIIB or IV disease received 1000 mg/m(2) gemcitabine and 25 mg/m(2) vinorelbine on days 1 and 8 and 75 mg/m(2) cisplatin on day 2, every 3 weeks. From December 1998 to May 1999, 31 patients (21 stage IV and 10 stage IIIB disease), with a median age of 59 years (range 40-72 years) were enrolled. The overall intent-to-treat response rate was 45% (95% confidence interval (CI): 27-64%) with 2 complete responders (CR) and 12 partial responders (PR), 7 patients had stable disease and 10 progressed. Median survival was 12.8 months (95% CI: 6.5-12.8+ months), median time to progression was 5.1 months (95% CI: 3.5-7.7 months), and the 1-year survival rate was 52.9% (95% CI: 36.7-76.2%). Patients with stage IIIB disease had a significantly longer overall survival than patients with stage IV disease (P=0.05). Transient World Health Organization (WHO) grade IV leucopenia, anaemia and thrombocytopenia occurred in 3 (10%), 2 (6%) and 3 (10%) patients, respectively. The predominant non-haematological toxicities were alopecia and nausea/vomiting. 15 patients (48%) had WHO grade II and III alopecia and 14 patients (45%) nausea/vomiting. The combination of gemcitabine, vinorelbine and cisplatin has demonstrated major antitumour efficacy in advanced NSCLC with a manageable toxicity profile.     

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.     

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.     

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.     

Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group.

PURPOSE: This phase III randomized trial compared two chemotherapy regimens, gemcitabine plus carboplatin and mitomycin, ifosfamide, and cisplatin, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). The regimens were compared with regard to effects on survival, response rates, toxicity, and quality of life. PATIENTS AND METHODS: Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy. Randomly assigned patients were to receive four cycles, each at 3-week intervals, of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2) on days 1 and 8 (GCa) or mitomycin 6 mg/m(2), ifosfamide 3g/m(2), and cisplatin 50 mg/m(2) on day 1 (MIC). RESULTS: Between February 1999 and August 2001, 422 patients (GCa, n = 212; MIC, n = 210) were randomly assigned in the United Kingdom. The majority of patients received the intended four cycles (GCa, 64%; MIC, 61%). There was a significant survival advantage for GCa compared with MIC (hazard ratio, 0.76; 95% CI, 0.61 to 0. 93; P = .008). Median survival was 10 months with GCa and 7.6 months with MIC (difference, 2.4 months; 95% CI, 1.0 to 4.0), and 1-year survival was 40% with GCa and 30% with MIC (difference, 10%; 95% CI, 3% to 18%). Overall response rates were similar (42% for GCa v 41% for MIC; P = .84). More thrombocytopenia occurred with GCa (P = .03), but this was not associated with increased hospital admission or fatality. GCa caused less nausea, vomiting, constipation, and alopecia and was associated with fewer admissions for administration and better quality of life. CONCLUSION: In patients with advanced NSCLC, GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC.