长春瑞滨联合卡铂治疗老年晚期非小细胞肺癌

目的：观察长春瑞滨(诺维本,NVB)联合卡铂化疗方案治疗老年晚期非小细胞肺癌患的临床疗效及不良反应。方法：对住院治疗的25例老年晚期非小细胞肺癌患采用NVB联合卡铂化疗方案,NVB25mg／m^2第1、8天,卡铂350mg／m^2第1天。每4周重复,至少治疗两周期,按标准评价疗效和毒副反应。结果：可评价患25例,有效率为48％,中位生存期7个月,1年生存率为32％。主要毒性反应为骨髓抑制、消化道反应及静脉炎,多数为Ⅰ～Ⅲ度反应。结论：NVB联合卡铂方案治疗老年晚期非小细胞肺癌临床疗效较好,毒性反应可以耐受。     

长春瑞滨加奥沙利铂治疗晚期非小细胞肺癌的临床研究

目的：评价长春瑞滨加奥沙利铂的两联化疗治疗晚期非小细胞肺癌的疗效和毒副反应。方法：长春瑞滨25mg／m^2 iv d1、8，奥沙利铂130mg／m^2 iv d2，3周重复。结果：全组25例，共完成81个周期平均3个周期(2～6个周期)，PR9例，客观有效率36％(9／25)，中位生存期8个月(4～18个月)，1年生存率20％(5／25)，主要毒副反应为骨髓抑制、消化道反应、静脉炎。结论：长春瑞滨加奥沙利铂的两联化疗在晚期非小细胞肺癌中有较好疗效，毒性可以耐受。     

Phase II study of the combination of vinorelbine and cisplatin in advanced non-small-cell lung cancer

Purpose To evaluate the efficacy and safety of combination chemotherapy with cisplatin and vinorelbine for the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods Eligible patients were those with measurable NSCLC. They were treated with two or more cycles of a regimen consisting of vinorelbine 25 mg/m² on days 1 and 8 and cisplatin 80 mg/m² on day 1 every 3 weeks.Results A total of 45 patients were enrolled. The response rate was 51.1% (23/45; 95% CI 35.8% to 66.3%). The median survival was 286 days with a 1-year survival rate of 40%. The median number of treatment cycles was 2. The major toxic effect was neutropenia of grade 3 or higher (84%). Nonhematological toxicities, including vomiting (62%), were mild (grade 2 or less). There were no treatment-related deaths.Conclusion The high response rate and good tolerability proved this combination therapy to be a safe and effective treatment for advanced NSCLC.This work was supported in part by a grant-in-aid from the Ministry of Health and Welfare (Tokyo, Japan) and from the Second Term Comprehensive 10-Year Strategy for Cancer Control.     

Carboplatin and docetaxel in advanced non-small-cell lung cancer: results of a multicenter phase II study

Background To evaluate the efficacy of carboplatin and docetaxel combination in patients with advanced non-small-cell lung cancer.Methods In a phase II study, patients with inoperable stage IIIB or stage IV non-small-cell lung cancer (ECOG performance status of 0 or 1) were treated with the combination of carboplatin AUC 5 mg/ml·min and docetaxel 80 mg/m² administered once every 3 weeks.Results A total of 45 patients were accrued to the study. The median age was 62 years and adenocarcinoma was the most common histology. Patients received a median of four cycles of chemotherapy. The objective response rate was 29% with a median survival of 11.9 months among evaluable patients. The 1-year survival rate was 47%. Febrile neutropenia (17%) was the most common hematological toxicity associated with the regimen whereas grade 3 fatigue (4%) was the major nonhematological toxicity.Conclusions The combination of carboplatin plus docetaxel is well tolerated and is effective for the treatment of patients with previously untreated advanced or metastatic non-small-cell lung cancer.This work was supported in part by Aventis Pharmaceuticals Inc.     

Phase I study of weekly cisplatin, vinorelbine, and concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer

Background The combination of chemotherapy and thoracic radiation therapy (TRT) is considered as a standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Although the frequent interaction of anticancer agents and irradiation may produce stronger radio-sensitizing effects, the daily administration of these agents is complicated. We therefore used weekly administration of these agents, and conducted a phase I study of weekly cisplatin, vinorelbine, and concurrent TRT. The purpose of this study was to identify the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT), and the recommended dose of this treatment. Methods Patients with locally advanced NSCLC were enrolled in this study. Both cisplatin and vinorelbine were given intravenously on a weekly schedule for 6 weeks, starting on the first day of TRT, i.e., on days 1, 8, 15, 22, 29, and 36. The total dose of TRT was 60 Gy. The dose of cisplatin was fixed at 20 mg/m² per week. The starting dose of vinorelbine was 15 mg/m² per week (dose level 1). Results Nine patients were enrolled in this study. All three patients at dose level 1 experienced DLTs. We decreased the dose of vinorelbine to 10 mg/m² per week (dose level 0). Two of the six patients at dose level 0 experienced DLTs. Therefore, dose level 1 was considered as the MTD, and dose level 0 as the recommended dose. The DLTs of this treatment were esophagitis, fatigue, infection, and hyponatremia. Conclusion The recommended dose of cisplatin is 20 mg/m² per week and that of vinorelbine is 10 mg/m² per week with standard TRT. A phase II study of this treatment is warranted. The results of this study were presented in part at the 43rd Annual Meeting of the Japan Lung Cancer Society in Fukuoka, Japan, November 21–22, 2002.     

Biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer

Purpose: Improving chemotherapeutic efficacy in non-small cell lung cancer (NSCLC) will require the development of new strategies to better use currently available agents. To assess the efficacy and safety of a biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer. Methods: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0–2 and normal organ function were eligible. Treatment consisted of cisplatin 100 mg/m² on day 1 plus gemcitabine, 1,000 mg/m² and vinorelbine 25 mg/m² on days 1 and 15 every 28 days. Results: Of the 40 patients enrolled and assessable for response, there were five (12.5%) with confirmed complete response and 14 (35%) with a confirmed partial response for an overall response rate of 47.5%. Nine patients had stable disease while 12 (30%) progressed. Median progression-free survival and overall survival for all patients were 6.3 and 11.1 months, respectively. Toxicity was principally hematologic, with grade 3–4 neutropenia in 30%, and grade 3–4 nausea/vomiting in 22.5%. There were no treatment-related deaths. Conclusions: The biweekly regimen of cisplatin, gemcitabine and vinorelbine is associated with a high rate of response, lesser toxicity than other three-drug regimens and no benefit of survival. Therefore, the regimen under study may be an appealing alternative when considering other treatment modalities for advanced lung cancer, such as neoadjuvant therapy.     

长春瑞滨联合卡铂治疗老年晚期非小细胞肺癌

目的观察长春瑞滨加卡铂联合化疗治疗老年晚期非小细胞肺癌患者的临床疗效和毒副反应。方法对24例≥70岁的老年晚期非小细胞肺癌患者采用长春瑞滨联合卡铂方案化疗长春瑞滨25mg/m2,静脉滴注,第1、8天;卡铂AUC=4~5,静脉滴注,第2天,每3周重复,至少治疗2周期。结果共完成63周期,中位数3周期,有效率33.33%,中位生存期10.25个月,1年生存率41.67%。主要毒副反应为骨髓抑制,发生率83.33%,其中Ⅰ度8.33%,Ⅱ度41.67%,Ⅲ度29.17,Ⅳ度4.17%。结论长春瑞滨联合卡铂方案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。     

长春瑞滨和卡铂联合同步放疗治疗晚期非小细胞肺癌观察

目的：评价国产长春瑞滨(盖诺)和卡铂联合同步放疗治疗晚期非小细胞肺癌的疗效及毒副反应。方法：106例Ⅲ期NSCLC患,分为二组,化放组在放疗的同时及放疗后进行4周期化疗,化疗用药盖诺25mg／m^2在每个周期的第1、8天静脉滴注给予;卡铂300mg／m^2第1天静脉滴注。单放组行单纯放疗。结果：化放组有效率71．4％,单放组有效率为42．0％。化放组的有效率明显高于单放组(P=0．008)。化放组和单放组的1、2年生存率分别为77．39％、30．33％和58．65％、15．75％,中位生存时间分别为18个月和13个月,其差异有显性(P=0．0407)。结论：盖诺和卡铂联合同步放疗是治疗晚期非小细胞肺癌的安全有效的治疗方法,值得进一步临床研究。     

Effect of vinorelbine monotherapy in taxane-treated patients with advanced non-small-cell lung cancer

Taxane-based chemotherapy now plays an important role in the first-line treatment on patients with advanced non-small-cell lung cancer (NSCLC). Recent attention has been focused on the treatment of patients with NSCLC who failed to respond to taxane-based chemotherapy. In the present article, we report the effect of single-agent vinorelbine (VNR) in 10 patients with NSCLC previously treated with taxanes. An antitumor effect was observed in five patients, resulting in a response rate of 50.0% (5/10). The absence of vinca alkaloid pretreatment was an important factor in the clinical response in these patients. Further study is warranted to investigate the clinical efficacy of VNR monotherapy in taxane-resistant NSCLC patients.     

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。     

长春瑞滨联合卡铂治疗晚期非小细胞肺癌的临床研究

目的:观察国产长春瑞滨联合卡铂治疗晚期非小细胞肺癌的临床疗效和毒副反应。方法:45例非小细胞肺癌患者均经细胞学或组织学证实,所有患者均进行长春瑞滨联合卡铂方案化疗,其中长春瑞滨25mg/m2,静脉注射,第1、5天;卡铂300mg/m2,静脉滴注,第1天,21天为1周期。结果:45例患者中,CR2例,PR21例,SD13例,PD9例,总有效率为51.1%。其中初治患者25例,CR PR14例,有效率56.0%;复治20例,CR PR6例,有效率30.0%。毒性反应主要为胃肠道反应和骨髓抑制,其次为局部红肿和疼痛等静脉炎表现。结论:长春瑞滨联合卡铂方案是治疗晚期非小细胞肺癌较为理想的方案之一。     

国产长春瑞滨低剂量持续静脉输注治疗非小细胞肺癌的临床研究

目的比较低剂量国产长春瑞滨(盖诺)持续120h静脉输注与传统的静脉推注疗法联合顺铂治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副反应。方法127例晚期NSCLC患者随机分为A、B两组。A组66例,盖诺10mg加入NS40ml中静推,然后将盖诺10mg加入NS500ml中持续静脉输注24h,连续5天,共120h,盖诺总剂量60mg,顺铂总量80mg/m2,d1(或分次给予);B组61例,盖诺40mg加入NS100ml中静滴,d1、d8,顺铂用法用量同前。结果A、B两组的有效率分别为42.4%和42.6%,中位生存期分别为37周和35周,中位进展时间分别为25周和23周,1年生存率分别为37.8%和36.1%。两组最常见的血液学毒性均为中性粒细胞减少,发生率分别为90.9%和91.8%,无统计学差异,但A组的Ⅲ~Ⅳ度骨髓抑制较B组明显为轻(P<0.05)。结论长春瑞滨持续120h静脉输注治疗NSCLC有效率、中位生存时间和1年生存率与静推疗法相似,而毒性较静脉推注为低,同时也降低了治疗费用,值得临床进一步研究。     

Phase II study of gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer

Purpose To evaluate the efficacy and safety of gemcitabine in combination with carboplatin at standard rate or fixed dose rate infusion in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods In this prospective study, patients with chemonaive advanced NSCLC were randomized to receive gemcitabine at a standard rate (gemcitabine 1,200 mg/m² over 30 min, the standard arm) or a fixed dose rate (gemcitabine 1,200 mg/m² over 120 min, the FDR arm) on days 1 and 8 every 3 week cycle. In both treatment arms, carboplatin at AUC of 5 was administered over 4 h following gemcitabine on day 1 of each cycle. Results From November 2003 to June 2005, a total of 42 patients, in which 7 (17%) patients had stage III_B disease and 35 (83%) had stage IV disease, were enrolled into this study. All patients were included in efficacy and toxicity assessment. No patient had a complete response. Seven (33%) patients in the standard arm and 10 (48%) in the FDR arm had a partial response. The median time to progression and median overall survival time in the standard arm was 5.4 months (95% CI, 3.8–7 months) and 11.5 months (95% CI, 8.2–14.8 months), respectively, while in the FDR arm was 6.5 (95% CI, 4.4–8.6 months) months, 12.0 months (95% CI, 11.3–12.7 months), respectively. The most frequently reported grade 3 or 4 hematological toxicities were thrombocytopenia (38% patients in the standard arm and 43% in the FDR arm) and neutropenia (24% in the standard arm and 33% in the FDR arm). Although hematological toxicity occurred in a little higher percent of patients in the FDR arm than in the standard arm, there were no discernible differences by statistical analysis in both treatment arms (P > 0.05). And significant nonhematologic toxicities were infrequent and tolerable in both arms. No significant difference existed also (P > 0.05). Conclusion In this phase II study, gemcitabine in combination with carboplatin either at standard rate or fixed dose rate infusion was clinically effective and well tolerated in patients with advanced NSCLC.     

Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy

Objectives

Chemotherapy-induced nausea and vomiting (CINV) is an unanswered problem in cancer therapy. We evaluated the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT₃) receptor antagonist, and dexamethasone in patients with advanced non-small-cell lung cancer (NSCLC) who received carboplatin-based first-line chemotherapy.

Methods

Chemotherapy-naïve patients with NSCLC were enrolled in this randomized phase-II study. Patients were randomized to standard antiemetic therapy with a 5-HT₃ receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic therapy. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during the 120 h post-chemotherapy.

Results

A total of 134 patients were assigned randomly to the aprepitant group or the control group. The aprepitant group and the control group showed an overall complete response rate of 80.3% (95% confidence interval (CI), 69.2–88.1%) and 67.2% (95% CI, 55.3–77.2%; odds ratio (OR), 0.50; 95% CI, 0.22–1.10; p = 0.085), respectively. Among patients taking carboplatin and pemetrexed, adding aprepitant significantly improved the complete response rate in the overall phase (83.8% in the aprepitant group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08–0.70; p < 0.01) and the delayed phase (86.5% in the aprepitant group and 59.1% in the control group; OR, 0.23; 95% CI, 0.07–0.65; p < 0.01).

Conclusion

Carboplatin-based chemotherapy has considerable emetic potential. Triple antiemetic therapy with aprepitant, a 5-HT₃ receptor antagonist, and dexamethasone improved the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy.     

Erlotinib in advanced non-small-cell lung cancer after gefitinib failure

Purpose  To evaluate the efficacy and safety of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib treatment. Patients and methods  Patients with advanced or metastatic NSCLC, who had progressed after gefitinib treatment, were included in this study; patients received erlotinib 150 mg/day until disease progression or intolerable toxicity. Results  Twenty-one patients were included in this study. Among them, 14 (66.7%) were male and 7 (33.3%) were female; median age was 63 years; 10 (47.6%) patients were smokers; 9 (42.9%)patients had squamous cell carcinoma subtype; 8 (38.1%) patients had adenocarcinoma subtype and 4 (19%) patients had the other NSCLC subtype. Out of 21 patients, 2 (9.5%) had PR and 4 (19.0%) had SD, giving an overall response rate of 9.5% and a disease control rate of 28.5%. The median TTP were 55 days, the median OS were 135 days. Two patients with PR to erlotinib treatment were female never smokers with adenocarcinoma histology and both had partial response to prior gefitinib treatment. Three of four patients with a SD to erlotinib treatment also had SD from prior gefitinib therapy. Smoking history, histology and response to erlotinib were significantly correlated with survival. The most common toxic effects were skin rash. Conclusions  Erlotinib may be an option for a more highly selected subset of patients, especially those who had already benefited from prior gefitinib treatment.     

Phase II trial of edatrexate plus carboplatin in metastatic non-small-cell lung cancer: a Southwest Oncology Group study

Background: Edatrexate and carboplatin are each active single agents in the treatment of non-small-cell lung cancer (NSCLC). Preclinical studies in NSCLC lines have demonstrated schedule-dependent synergy of edatrexate followed by carboplatin. In a phase I trial, we demonstrated the tolerability of this combination, the ability of ice-chip cryotherapy to ameliorate dose-limiting mucositis, and promising activity in NSCLC. This phase II trial (SWOG 9207) was undertaken to investigate the efficacy of this regimen in stage IV NSCLC. Methods: A total of 24 patients with stage IV disease were accrued to this Southwest Oncology Group (SWOG) multicenter study. Treatment consisted of edatrexate 80 mg/m² (50% dose on day 8) intravenously weekly for 5 weeks, then every other week, and carboplatin 350 mg/m² every 28 days. Results: Of the 24 patients, 23 were assessable for toxicity and response; one was ineligible for study entry. Myelosuppression was the most significant toxicity; grade 3–4 neutropenia was seen in 8/23 patients. Two patients died of neutropenic sepsis during the first cycle of therapy, in both instances associated with the presence of pleural effusions. Although mild mucositis was common, it was dose-limiting (grade 3) in only three patients. Objective response was observed in 3/23 patients (13%). The median survival time was 7 months, and 30% of patients remained alive at one year. Conclusions: This study suggests that ice-chip cryotherapy is effective in reducing the severity of mucositis typically associated with this edatrexate schedule of administration. However, unexpectedly severe myelosuppression resulted in death from neutropenic sepsis in two patients with third space fluid collections, leading to a protocol amendment to exclude such patients from study entry. Furthermore, response and median survival with this dose schedule of edatrexate and carboplatin do not appear to be improved compared to other chemotherapeutic regimens tested by SWOG in this patient population. Received: 12 August 1996 / Accepted: 8 May 1997     

吉非替尼单药治疗晚期非小细胞肺癌

目的观察吉非替尼单药治疗晚期非小细胞肺癌（NSCLC）的疗效和不良反应。方法对50例晚期NSCLC患者给予吉非替尼250mg／d口服治疗,观察疗效和不良反应,采用欧洲癌症研究和治疗组织生活质量调查核心问卷QLQ-C30和简明乏力量表（BFI）对患者的生活质量及临床症状的改善进行评价,观察疾病进展时间（TTP）和中位生存时间（MST）。结果50例晚期NSCLC患者中,无完全缓解者,部分缓解（PR）8例（16．0％）,临床获益率为60．0％,临床获益率与性别、病理类型及吸烟史有关。到随访截止日期,50例患者中,20例（40．0％）存活,其MST为13个月;30例死亡患者TTP为5个月,MST为6个月。PR患者MST为9个月。综合生活质量改善率为58．0％,乏力症状缓解率为52．6％,出现症状缓解的中位时间为15d。不良反应主要为Ⅰ、Ⅱ度皮疹和腹泻,对症处理后可缓解。3例既往因放疗而引起放射性肺炎的患者中,2例放射性肺炎加重。结论吉非替尼有明显抗肿瘤作用,能明显提高晚期NSCLC患者的生活质量,改善临床症状,不良反应可以耐受。     

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.     

Combination effects of cisplatin,vinorelbine and irinotecan in non-small-cell lung cancer cell lines in vitro

 Purpose: Isobologram analysis has been widely used for evaluating the combined effect of two antitumor drugs in vitro as a pre-clinical screening test. In this study, we tried to extend two-dimensional isobologram analysis to three dimensions for evaluating the effects of a three-drug combination. Methods: We selected three anticancer agents, cisplatin, vinorelbine and irinotecan. Each of them has been classified as having good single-agent activity against non-small-cell lung cancer (NSCLC). Human NSCLC cell lines (EBC-1, PC-3, RERF-LC-MS) were incubated for 4 days in the presence of the three drugs and cytotoxic activities were determined by a tetrazolium-based colorimetric assay (MTT assay). The data were analyzed by three dimensional isobologram analysis. Results: The effects of the three drugs were additive against EBC-1 (a squamous cell carcinoma cell line), subadditive against PC-3 (an adenocarcinoma cell line) and from subadditive to supraadditive against RERF-LC-MS (an adenocarcinoma cell line). Conclusions: Our findings suggest that the effects of cisplatin, vinorelbine and irinotecan incombination are additive against NSCLC in vitro. These results encourage clinical trials of the three agents in combination chemotherapy for the treatment of NSCLC. Received: 8 December 1995/Accepted: 18 May 1996