长春瑞滨联合顺铂与长春瑞滨联合奥沙利铂治疗晚期NSCLC的随机对照临床研究

背景与目的 长春瑞滨联合顺铂是治疗晚期非小细胞肺癌（NSCLC）的主要化疗方案之一，但副反应较重。本研究的目的是比较长春瑞滨联合顺铂与长春瑞滨联合奥沙利铂治疗晚期NSCLC的临床疗效和毒副作用。方法 126例不能手术或术后复发转移的Ⅲ～Ⅳ期NSCLC患者随机分组，接受长春瑞滨联合顺铂或长春瑞滨联合奥沙利铂方案，化疗2～3个周期后评价疗效。结果 长春瑞滨联合顺铂组有效率为48．4％，部分缓解率为45．2％；长春瑞滨联合奥沙利铂组有效率为42.2％，部分缓解率为40．6％，两组近期疗效比较无显著性差异（P〉0．05）。长春瑞滨联合顺铂组Ⅲ＋Ⅳ度白细胞下降25例（40．3％），长春瑞滨联合奥沙利铂组仅10例（15．6％），两组比较有显著性差异（P＜0．05）；Ⅲ＋Ⅳ度消化道反应在长春瑞滨联合顺铂组为11例（17．7％），长春瑞滨联合奥沙利铂组仅3例（4．7％），亦有显著性差异（P〈0．05）。长春瑞滨联合顺铂组发生神经毒性7例（11．7％），长春瑞滨联合奥沙利铂组有60例（93．8％），有显著性差异（P〈0．05）。结论 长春瑞滨联合顺铂和长春瑞滨联合奥沙利铂是治疗晚期NSCLC较有效的方案。与长春瑞滨联合顺铂方案相比，长春瑞滨联合奥沙利铂方案疗效相似，消化道反应及血液学毒性较轻，而神经毒性反应发生率较高。     

奈达铂联合长春瑞滨治疗65例转移癌

[目的]观察奈达铂联合长春瑞滨治疗转移癌的临床疗效及毒副反应。[方法]125例转移癌患者,随机分为奈达铂组（65例）和顺铂组（60例）。奈达铂组：奈达铂80mg／m^2,d1;长春瑞滨25mg／m^2,静脉滴注,d1、d8。顺铂组：顺铂80mg／m^2,d1;长春瑞滨25mg／m^2,d1、d8。21d为1个周期,共治疗4-6个周期。[结果]奈达铂组总有效率50．8％,其中转移性鳞癌有效率64．7％,转移性腺癌有效牢35．5％（P〈0．05）。顺铂组总有效率50．0％,其中转移性鳞癌有效率51．7％．转移性腺癌有效率48．4％（P〉0．05）。奈达铂组的主要毒副反应为胃肠道反应和肾功能损伤,但均较顺铂组轻。两组中位疾病进展期和中位生存期比较无显著性差异。[结论]奈达铂联合长春瑞滨治疗转移癌疗效与顺铂组相当。但毒副反应较轻,尤其适用于转移性鳞癌。     

多西紫杉醇联合顺铂与长春瑞宾联合顺铂治疗晚期非小细胞肺癌的临床研究比较

目的 探讨多西紫杉醇(多帕菲)联合顺铂与长春瑞宾联合顺铂治疗晚期非小细胞肺癌(NSCLC)的临床疗效、毒副反应.方法 将103例晚期NSCLC患者随机分为多西紫杉醇 顺铂组(54例)和长春瑞宾 顺铂组(49例).多西紫杉醇 顺铂组(A组):多帕菲75 mg/m2 顺铂80 mg/m2;长春瑞宾 顺铂组(B组):长春瑞宾25 mg/m2 顺铂80 mg/m2;两组均为每3周重复.结果 入组的103例中101例可评价疗效,A组和B组有效率分别为40.4%和36.7%,有效率相似.不良反应主要为中性粒细胞减少、贫血、粒细胞减少性发热、其它发热、脱发、恶心呕吐及乏力.Ⅲ～Ⅳ度中性粒细胞减少率A组为13.0%,而B组为34.7%,两组间存在显著差异(P=0.032);Ⅲ～Ⅳ度恶心、呕吐发生率A组为11.1%,B组为32.7%,两组间存在显著差异(P=0.017).其余不良反应两组间相似.结论 多西紫杉醇联合顺铂方案和长春瑞宾联合顺铂方案在治疗晚期NSCLC方面具有一定的疗效且两者的疗效相似,但多西紫杉醇联合顺铂组的不良反应较低,患者更易耐受.     

NC与GC方案治疗耐药晚期乳腺癌近期疗效对照研究

 目的 研究吉西他滨与长春瑞滨（商品名：诺维本）分别联合顺铂治疗对蒽环类和紫杉类药物耐药的晚期乳腺癌患者的近期疗效及毒副反应。方法 经病理组织学或细胞学证实的46例晚期乳腺癌患者，随机分为两组，吉西他滨联合顺铂组（A组）23例，以吉西他滨1000 mg／m2静脉滴注，第1天、第8天；顺铂25 mg／m2静脉滴注，第1天至第3天。长春瑞滨联合顺铂组（B组）23例，以长春瑞滨25 mg／m2，第1天、第8天溶于生理盐水100 ml中快速静脉滴注。顺铂用法同A组。两方案均每3周重复，2个周期以上评价疗效。结果 两组的有效率分别为60.8 %（14／23）和56.5 %（13／23），两组比较差异无统计学意义（P＞0.05）。A组Ⅲ～Ⅳ度血小板减少高于B组，但B组Ⅲ～Ⅳ度白细胞减少及静脉炎相对较明显。结论 NC与GC方案治疗耐药晚期乳腺癌有较高的缓解率，不良反应较轻。     

奈达铂治疗晚期非小细胞肺癌临床观察

目的：观察吉西他滨联合奈达铂与联合顺铂方案治疗晚期非小细胞肺癌（NSCLC）的疗效和安全性。方法：60例中晚期非小细胞肺癌患者,其中吉西他滨联合奈达铂化疗方案组（GN组）30例,吉西他滨1000mg/m^2,第1、8天,静脉滴注30分钟,奈达铂80mg/m^2,第2天,滴注时间大于1小时;吉西他滨联合顺铂化疗方案组（GP组）30例,吉西他滨1 000mg/m^2,第1、8天,静脉滴注30分钟,顺铂80-100 mg/m^2,分3d,常规水化利尿。以上2组方案均21天为一个周期。结果：GN组有效率36.67%,GP组有效率40.00%,两组间无显著差异（P〉0.05）;GP组胃肠道反应（80%）发生率明显高于GN组（56.7%）（P〈0.05）;两组肾脏毒性无明显差异;两组白细胞下降发生率分别为56.7%和50.0%,奈达铂组明显（P〉0.05）;血小板下降GN组（73.3%）较GP组（66.7%）显著（P〉0.05）,但无统计学差异。结论：吉西他滨联合奈达铂治疗晚期NSCLC的有效率不低于吉西他滨联合顺铂方案,胃肠道毒性较轻,不良反应主要为骨髓抑制及过敏反应。     

多西他赛联合顺铂一线治疗晚期非小细胞肺癌

目的：比较多西他赛及长春瑞滨联合顺铂一线治疗晚期非小细胞肺癌的疗效和不良反应.方法：67例晚期非小细胞肺癌患者随机分为2组.多西他赛组：多西他赛37.5mg/m^2,d1,8,顺铂80 mg/m^2,分为3天,d1～3.长春瑞滨组：长春瑞滨25 mg/m^2,d1,8,顺铂用法同前.结果：多西他赛组有效率50%,1年生存率46.9%,2年生存率15.6%.长春瑞滨组有效率25.7%,1年生存率31.4%,2年生存率11.4%（P＜0.05）.主要毒副作用为骨髓抑制、恶心、呕吐.结论：一线治疗晚期非小细胞肺癌多西他赛较长春瑞滨联合顺铂疗效高,生存期长.     

伽玛刀联合长春瑞滨、顺铂治疗局部晚期肺癌疗效观察简

目的：探讨体部伽玛刀联合长春瑞滨、顺铂治疗局部晚期非小细胞肺癌的临床疗效及不良反应。方法：自2008年1月-2010年7月,对101例非小细胞肺癌患者按治疗方法分为伽玛刀联合长春瑞滨、顺铂（联合组）52例和单纯应用长春瑞滨、顺铂（对照组）49例,比较两组治疗后的近期疗效、生存期及不良反应。结果：联合组、对照组有效率分别为82．69％和53．06％,两组1年生存率分别为69．23％,42．86％。联合组的急性放射性肺损伤发生率11．54％,急性放射性食管损伤发生率9．62％,均为1—2度。两组的血液毒性主要表现为白细胞下降,另外还合并有恶心、呕吐等,联合组发生几率明显高于对照组,但经过对症治疗均能顺利完成治疗。结论：伽玛刀联合长春瑞滨、顺铂治疗能显著提高局部晚期肺癌患者的近期疗效、生存时间;白细胞下降、恶心、呕吐等不良反应较单纯化疗组也明显增加,有部分患者还会出现急性放射性肺损伤,急性放射性食管损伤,但经过对症处理基本恢复正常不影响治疗。     

奈达铂或顺铂联合紫杉醇治疗晚期食管癌的临床观察

目的评价并比较奈达铂/顺铂联合紫杉醇治疗晚期食管癌的疗效和不良反应。方法回顾性分析2006年至2011年收治的80例接受奈达铂联合紫杉醇（41例）或顺铂联合紫杉醇（39例）治疗的晚期食管癌患者,对比两种治疗方法的疗效及不良反应。结果奈达铂联合紫杉醇组（TN组）缓解率为26.8%;顺铂联合紫杉醇组（TP组）缓解率为23.1%,两组间差异无统计学意义（P=0.603）;TN组和TP组的中位疾病进展时间（time to progress,TTP）和中位总生存时间（overall survival,OS）分别为6个月和5个月、11个月和10个月,差异具有统计学意义（P=0.003,P=0.068）。常见的毒副反应主要是消化道毒性,血液学毒性和脱发。奈达铂组消化道毒性发生率及严重程度显著低于顺铂组,差异具有统计学意义（P=0.0001）。结论奈达铂联合紫杉醇治疗晚期食管癌患者其疗效和总生存与顺铂联合紫杉醇相似,但是在疾病无进展时间和消化道毒性发生率及严重程度上,奈达铂较顺铂有着显著的优势。     

58例含长春瑞滨方案治疗(蒽环类/紫杉类治疗后)复发转移乳腺癌的临床观察

目的：观察含长春瑞滨方案对蒽环类/紫杉类药物治疗后复发转移性乳腺癌的有效性和安全性。方法：蒽环类/紫杉类药物治疗后复发转移性乳腺癌患者61例,其中58例可评价疗效;长春瑞滨联合顺铂（NP）41例,长春瑞滨25mg/m^2,第1天和第8天,静脉滴注;顺铂75～80mg/m^2,静脉滴注,分割为2～5天,3周为一周期;长春瑞滨联合卡培他滨或替加氟（NF）17例,长春瑞滨用法同NP组,卡培他滨800～1000mg/m^2,分早晚两次服用,第1～14天,或替加氟600mg/m^2,第2～6天,3周为一周期。化疗过程中注意观察不良反应,根据不良反应的程度调整药物用量。每两周期评价疗效。结果：长春瑞滨联合顺铂（NP）组,CR2例（4.9%）,PR23例（56.1%）,SD14例（34.1%）,PD2例（4.9%）,有效率为61.0%;长春瑞滨联合卡培他滨或替加氟（NF）组,CR1例（5.9%）,PR8例（47.1%）,SD7例（41.2%）,PD1例（5.9%）,有效率52.9%。常见的不良反应主要为骨髓抑制、胃肠道反应、手足综合症、神经毒性等。结论：含长春瑞滨方案治疗蒽环类/紫杉类药物治疗后复发转移乳腺癌疗效确切,毒性可耐受,是治疗复发转移性乳腺癌的较好方案。     

长春瑞滨联合奈达铂治疗耐药性晚期口腔颌面部肿瘤的临床观察

目的 探讨长春瑞滨联合奈达铂治疗顺铂耐药的晚期口腔颌面部肿瘤的疗效和安全性。方法 收集2012年8月至2015年7月一线接受以顺铂为基础的化疗失败的42例晚期口腔颌面部肿瘤患者,均给予长春瑞滨联合奈达铂方案化疗。长春瑞滨25 mg／m2静滴,d1、d8;奈达铂 80 mg／m2静滴,d1、d2, 21天为1个周期。采用RECIST 1.1版标准评价近期疗效,NCI CTC 4.0版标准评价不良反应。结果 42例患者均可评价近期疗效,有效率为45.2％,疾病控制率为73.8％,中位无进展生存时间为7个月（95％CI：6.06～7.94个月）,中位总生存时间为13个月（95％CI：10.91～15.09个月）。主要毒副反应为骨髓抑制、恶心呕吐,1～2级居多。结论 长春瑞滨联合奈达铂治疗顺铂耐药的晚期口腔颌面部肿瘤疗效较好,耐受性好,安全性高,值得进一步临床观察和研究。     

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。      

国产奈达铂联合长春瑞滨治疗晚期非小细胞肺癌

目的：观察国产奈达铂（NDP）联合长春瑞滨（NVB）治疗中晚期非小细胞肺癌（NSCLC）的疗效和毒副反应。方法：36例经病理组织学证实的NSCLC患者，临床分期III B～Ⅳ期，失去手术机会，应用NDP80～100mg／m^2，静脉滴注，d1，NVB25～30mg／m^2，快速静脉滴注，d1、d8，28天为1个周期，用药3个周期后进行评价，并观察同期采用顺铂（PDD）联合NVB化疗的III B～Ⅳ期NSCLC患者40例作为对照。结果：NDP组36例，CR 2例，PR 14例，NC 14例，PD 6例，总有效率（CR＋PR）为44．4％，PDD组有效率45．O％；中位生存时间NDP组6.5个月，PDD组6．7个月，无明显差异（P〉0．05）。NDP组主要毒副反应为骨髓抑制，白细胞下降率80．6％，III～1V度下降为36．1％，其次是消化道反应，未发现明显的肝肾毒性、周围神经毒性等。结论．围产NDP群会NVB治疗中晚期NSCLC疗效与PDD联合NVB相当，但毒副反应减轻，耐受性好。     

枢丹预防大剂量顺铂化疗所致呕吐的临床效果

目的观察枢丹的止吐疗效和毒性。方法对３０例接受大剂量顺铂化疗的患者,采用随机自身对照的方法,比较枢丹和枢复宁在相等剂量下的疗效和毒性。结果枢丹能有效预防顺铂所致的恶心、呕吐,其止吐效果与枢复宁相似。两药的止吐有效率分别为７０．０％和６３．３％,完全缓解率分别为５６．７％和５３．３％。两药的疗效无统计学差异,且毒副反应小。结论枢丹为肿瘤化疗安全、有效的止吐药,值得临床推广应用     

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 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.     

Effect of vinorelbine, ifosfamide, and cisplatin combination chemotherapy in advanced non-small-cell lung cancer

Cisplatin-based chemotherapy is being tried in the treatment of nonoperable cases of non-small-cell lung cancer (NSCLC). However, the prognosis is unfavorable and to improve survival, clinical studies using various combinations of a variety of drugs as well as experimental material are in progress. We compared the efficacy and toxicities of combination chemotherapy using different doses of vinorelbine and ifosfamide with a constant dose of cisplatin in this study. Patients diagnosed with inoperable stage III or IV NSCLC between June 1997 and December 1998 were included. Cisplatin was administered at a constant dose of 80 mg/m2 on day 5, whereas vinorelbine on days 1 and 5 and ifosfamide on day 5 were administered in one of two different doses. In arm A, vinorelbine 25 mg/m2 and ifosfamide 3.0 g/m2 were administered. In arm B, vinorelbine 20 mg/m2 and ifosfamide 2.5 g/m2 were administered. Also, we reviewed for phase II and III studies that test 1) cisplatin, 2) vinorelbine monotherapy, and 3) vinorelbine/cisplatin/ifosfamide combination chemotherapy for stage IIIb-IV non-SCLC. Summation dose intensity (SDI) was calculated in each published and current study. Twenty patients in arm A and 35 patients in arm B were available for evaluation. There was no difference in patient activity, pathologic diagnosis, and differentiation or stage between the two arms. The median number of cycles was four in both arms. The response rate was 50% in arm A and 30% in arm B. The median survival times for arm A and B were 40 and 42 weeks, respectively, whereas the SDI was 1.94 and 1.7, respectively. More than grade III leukopenia was observed in 28.9% in arm A, which is more frequent than the 17.2% in arm B. There was a significant correlation between the SDIs and response rates and median survival (r2 = 0.629, p = 0.001; r2 = 0.453, p = 0.001, respectively). Although the follow-up period is relatively short, the survival time was similar in both arms. Because a high response rate may not be followed by a high survival time in combination chemotherapy of NSCLC, further studies on the appropriate dose of individual agents with regard to the relationship between response rate, severity, and incidence of toxicities and survival rate should be carried out.     

Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient's quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. PATIENTS AND METHODS: Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. RESULTS: Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. CONCLUSION: Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity.     

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.     

Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study

PURPOSE: The superiority of chemoradiotherapy (CRT) over radiation alone in locally advanced non-small cell lung cancer (NSCLC) has been proven, but the relative merits of a concurrent schedule versus their sequential administration are less clear. This study compared the safety and efficacy of concurrent and sequential CRT, with chemotherapy (CT) consisting of a cisplatin and vinorelbine regimen, in patients with locally advanced NSCLC. PATIENTS AND METHODS: One hundred and two previously untreated patients (aged 42-75 years) with locally advanced, stage IIIA (n = 15) or stage IIIB (n = 87) NSCLC were entered into the study. The CT schedule consisted of up to four cycles of cisplatin 80 mg/m(2) on day 1, and vinorelbine 25 mg/m(2) at the first and fourth cycles (12.5 mg/m(2) during the 2nd/3rd cycles) on days 1, 8, 15 of a 28-day cycle. Radiotherapy (RT) was prescribed at a dose of 60 Gy/30 fractions, given as five fractions per week for 6 weeks. In the concurrent arm (arm A), RT was started on day 4 of cycle 2; whilst in the sequential arm (arm B), RT started within 2 weeks after completion of CT. Fifty-two patients were randomized to concurrent treatment and 50 to the sequential schedule. RESULTS: Overall survival was significantly longer in arm A (median survival 16.6 months) versus arm B (median survival 12.9 months) (P = 0.023 by means of log-rank test; hazard ratio HR = 0.61, 95% CI of HR (0.39-0.93)), and time to progression (TTP) was also significantly longer in arm A (median time to progression 11.9 months) versus arm B (median time to progression 8.5 months) (P = 0.024 by means of log-rank test; HR = 0.62, 95% CI of HR (0.38-0.93)). Ninety-eight patients were evaluable for response and 101 for toxicity. The overall response rate was significantly higher in arm A, 80% (with 21% complete response (CR)) compared with 47% (with 17% CR) in arm B (P = 0.001 by means of chi(2)-test). WHO grade 3 or 4 toxicity was more frequent in arm A than in arm B, with a significantly greater incidence of leucopenia (53% versus 19%, P = 0.009 by means of chi(2) test) and nausea/vomiting (39% versus 15%, P = 0.044 by means of chi(2) test). There were no treatment related deaths. CONCLUSION: In this study population, concurrent CRT demonstrated significant benefit in terms of response rate, overall survival and time to progression over sequential CRT. The concurrent CRT schedule was associated with higher toxicity; however, the adverse event profile was acceptable in both arms.     

Mature results from a randomized Phase II trial of cisplatin plus 5-fluorouracil and radiotherapy with or without tirapazamine in patients with resectable Stage IV head and neck squamous cell carcinomas

BACKGROUND: The objective of this article was to report the results from a randomized trial that evaluated the efficacy and toxicity of adding tirapazamine (TPZ) to chemoradiotherapy in the treatment of patients with head and neck squamous cell carcinomas (HNSCC). METHODS: Sixty-two patients with lymph node-positive, resectable, TNM Stage IV HNSCC were randomized to receive either 2 cycles of induction chemotherapy (TPZ, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (TPZ, cisplatin, and 5-FU) or to receive the same regimen without TPZ. Patients who did not achieve a complete response at 50 Grays underwent surgical treatment. Stratification factors for randomization included tumor site, TNM stage, and median tumor oxygen tension. The primary endpoint was complete lymph node response. RESULTS: The addition of TPZ resulted in increased hematologic toxicity. There was 1 treatment-related death from induction chemotherapy. The complete clinical and pathologic response rate in the lymph nodes was 90% and 74% for the standard treatment arm and the TPZ arm, respectively (P = .08) and 89% and 90% at the primary site in the respective treatment arms (P = .71). The 5-year overall survival rate was 59%, the cause-specific survival rate was 68%, the rate of freedom from recurrence was 69%, and the locoregional control rate was 77% for the entire group. There was no difference with regard to any of the outcome parameters between the 2 treatment arms. The significant long-term toxicity rate also was found to be similar between the 2 arms. CONCLUSIONS: The addition of TPZ increased hematologic toxicity but did not improve outcomes in patients with resectable, Stage IV HNSCC using the protocol administered this small randomized study. The combination of induction and simultaneous chemoradiotherapy resulted in excellent survival in these patients.