三维适形调强放疗同步顺铂化疗联合尼妥珠单抗治疗局部晚期鼻咽癌的临床疗效

目的 观察三维适形调强放疗同步顺铂化疗联合分子靶向药物尼妥珠单抗治疗局部晚期鼻咽癌患者的临床疗效、耐受性及安全性。方法 选取本院收治的初治局部晚期鼻咽癌患者40例,采用三维适形调强放疗同步顺铂化疗联合分子靶向药物尼妥珠单抗治疗。三维适形调强放疗靶区剂量PGTVnx及PGTVnd均为69.96~73.92 Gy、PTV-1为60~66 Gy、PTV-2为54~56 Gy,共分割33次。化疗方案：顺铂80 mg/m2,静滴,3周为1个周期,每个周期的首日使用,共2个周期;放疗的第1天给予尼妥珠单抗（泰欣生）100 mg,每周1次,共8周。随访观察患者治疗的临床疗效、耐受性及安全性。结果 40例患者均按计划完成治疗,所有患者至少随访24个月,随访率100%,在随访期内1例局部进展。治疗后6个月评价,鼻咽病灶和淋巴结的有效率均为97.5%。治疗期间发生Ⅲ级骨髓抑制9例,Ⅲ级口腔黏膜炎8例,无Ⅳ级毒副反应发生。结论 三维适形调强放疗同步顺铂化疗联合分子靶向药物尼妥珠单抗治疗局部晚期鼻咽癌的近期疗效显著,耐受性及安全性良好,值得临床推广应用。     

调强放疗联合多西他赛和尼妥珠单抗治疗食管癌的疗效观察

目的:评价调强放疗联合多西他赛和尼妥珠单抗治疗食管癌的疗效和安全性。方法:55例不能手术或拒绝手术的中晚期食管癌患者根据入选标准随机分成调强放疗联合每周多西他赛和尼妥珠单抗(治疗组)和同期放化疗(对照组),治疗组在调强放疗的同时给予多西他赛20-30mg/m2,静脉滴注,尼妥珠单抗200mg,静脉滴注,每周1次,连续6周,在放疗第一天同时进行。两组化疗和调强放疗方法相同。结果:治疗组与对照组完全缓解率(CR)分别为53.8%和46.2%,有效率(CR+PR)分别为84.6%和73.1%。1、2、3年局控率分别为85.7%、67.9%、57.1%和70.4%、63.0%、51.9%;生存率分别为71.4%、53.6%、39.3%和63.0%、40.7%、29.6%。治疗组近期毒副反应尤其是放射性食管炎及Ⅰ、Ⅱ度骨髓抑制较对照组大,有1例因放射性食管炎中断治疗,其他经处理后均能顺利完成治疗。远期并发症以食管狭窄为主,两组无明显差异。结论:调强放疗联合每周多西他赛和尼妥珠单抗治疗较同期放化疗组疗效好,可提高中晚期食管癌的近期和中远期疗效,且毒副反应患者能耐受。     

三维适形调强放疗同步奈达铂化疗联合尼妥珠单抗靶向治疗鼻咽癌患者的疗效

目的探讨三维适形调强放疗同步奈达铂化疗联合尼妥珠单抗靶向治疗鼻咽癌的临床疗效。方法选取2017年1月至2018年1月间广东医科大学附属医院收治的68例鼻咽癌患者,根据治疗方式不同分为观察组和对照组,每组34例。对照组患者采用三维适形调强放疗同步奈达铂化疗治疗,观察组患者在对照组基础上联合尼妥珠单抗靶向治疗,比较两组患者的临床疗效及不良反应发生情况。结果随访9个月后,观察组患者总有效率为79. 4%,高于对照组的55. 9%,差异有统计学意义(P <0. 05)。两组患者的不良反应发生情况比较,差异均无统计学意义(均P> 0. 05)。结论三维适形调强放疗同步奈达铂化疗联合尼妥珠单抗靶向治疗鼻咽癌患者的近期疗效、安全性及耐受性均良好,值得临床运用。     

局部晚期鼻咽癌放疗联合顺铂或尼妥珠单抗的疗效比较

目的 比较局部晚期鼻咽癌患者TPF方案诱导化疗后放疗联合顺铂或尼妥珠单抗靶向治疗的疗效和不良反应。方法 对2012—2013年间随机分组收治的 60例Ⅲ—Ⅳ_b期鼻咽癌患者进行分析,其中对照组 32例、研究组 28例。两组患者均先行3周期TPF方案诱导化疗,对照组放疗同步顺铂40 mg/m²,1 次/周共7周,研究组放疗前1周开始使用尼妥珠单抗200 mg,1 次/周共7周。生存分析采用Kaplan-Meier法并Logrank检验,近期疗效和不良反应采用χ²检验。结果 对照组CR率97%、PR率3%,研究组CR率96%、PR率4%(P=0.923)。3年PFS对照组为88%,研究组为79%(P=0.352),3年OS对照组为97%,研究组为89(P=0.268)。但疗中骨髓抑制、重度乏力、恶心呕吐反应研究组较轻(P=0.002、0.008、0.001)。结论 放疗联合顺铂与放疗联合尼妥珠单抗靶向治疗局部晚期鼻咽癌患者的疗效无明显差别,但放疗联合靶向治疗的不良反应明显减轻。     

调强放疗联合西妥昔单抗及顺铂治疗晚期鼻咽癌

摘 要 目的: EGFR与鼻咽癌关系密切，西妥昔单抗是一种特异性阻断EGFR的单克隆抗体。观察调强适型放射治疗联合西妥昔单抗(cetuximab)及顺铂（cisplatin ,又称DDP）方案治疗晚期鼻咽癌的有效性和安全性。方法: 2007年7月至2007年12月共8例入组，其中初治鼻咽癌7例，复发鼻咽癌1例，所有病例均为Ⅲ、Ⅳ期；所有患者都签署知情同意书，研究报伦理委员会批准。治疗方法包括调强放疗、顺铂、西妥昔单抗（400 mg/m2，放射治疗前1周；250 mg/m2，每周1次，放疗期间维持）。结果: 8例均完成调强放疗。8例完成西妥昔单抗治疗4～8疗程，平均6个疗程；3例因肝功异常未行同期化疗，3例完成DDP 30 mg/m2化疗4～7疗程，1例完成DDP 100 mg/m2化疗2疗程，1例完成DDP 100 mg/m2化疗1疗程。8例均出现皮肤痤疮样皮疹，主要急性毒性反应为黏膜炎和骨髓抑制；黏膜炎8例；白细胞下降3例；3个月后所有反应为0～1级。8例均达完全缓解(complete remission,CR)，1例患者综合治疗后3个月出现肋骨转移。结论: 调强放疗联合西妥昔单抗及顺铂方案治疗晚期鼻咽癌的不良反应主要为口咽黏膜炎和疼痛较重，有2例不可耐受，建议降低西妥昔单抗的剂量。近期疗效令人满意，远期疗效尚需观察。     

长疗程尼妥珠单抗联合放化疗治疗局部晚期鼻咽癌的可行性

目的:评价长疗程尼妥珠单抗(nimotuzumab)联合调强放疗和化疗治疗局部晚期鼻咽癌有效性和安全性.方法:分析从2008年11月至2014年3月在浙江省肿瘤医院39例确诊为Ⅲ-Ⅳ期鼻咽癌患者,其中男性29例,女性10例;Ⅲ期20例,Ⅳa期14例,Ⅳb期5例.患者接受长疗程尼妥珠单抗联合调强放、化疗,尼妥珠单抗200 mg/次,1次/周,所有患者治疗9 ～18周.观察长疗程尼妥珠单抗联合调强放、化疗的疗效及毒副作用,参考RTOG标准分析患者急、慢性毒副作用;采用Kaplan-Meier方法、Log-rank法检验分析生存情况.结果:所有患者接受9周期以上尼妥珠单抗联合调强放、化疗的治疗后,中位随访时间46月(22～86个月),3年无局部复发生存率(LRFS)、无区域复发生存率(RRFS)、无远处转移生存率(DMFS)、PFS和OS分别为92.1％、89.7％、82.5％、77.6％和86.8％.单因素分析显示临床分期和新辅助化疗周期对生存率重要影响(3年DMFSⅢ、Ⅳ期分别为100.0％和63.2％ (P ＜0.01);3年LRFS 1～2周期、3～4周期分别为75.0％和96.8％(P＜0.05).结论:长疗程尼妥珠单抗联合调强放疗、化疗提高局部晚期鼻咽癌的疗效,并不增加毒、副作用,其远期疗效有待于长期随访结果.     

尼妥珠单抗联合放疗加同期替莫唑胺治疗高分级胶质瘤的初步研究

背景与目的：尼妥珠单抗（nimotuzumab）是抗人表皮生长因子受体（epithelial growth factor receptor,EGFR）人源化单克隆抗体,能够抑制肿瘤细胞增殖并增加放化疗敏感性。本研究运用前瞻性方法对尼妥珠单抗联合放疗加同期替莫唑胺（temozolomide,TMZ）治疗高分级的脑胶质瘤（high-grade glioma,HGG）患者的不良反应和近期疗效进行初步观察。方法：2008年7月—2009年6月期间共17例HGG患者入组,均采用TMZ同期放化疗加TMZ辅助化疗,其中12例新诊断为HGG的患者放疗总剂量为60Gy/30次,3例复发HGG患者为50Gy/25次,2例脑干复发HGG患者为40Gy/20次;放疗期间每天口服TMZ50mg/m2,放疗结束后4周循环口服TMZ;放疗期间每周静脉滴注尼妥珠单抗注射液。记录治疗反应,计算6个月无疾病进展生存率和总生存率。结果：本组病例急性不良反应多为Ⅰ～Ⅱ级,没有Ⅲ级以上不良反应,有1例因发生Ⅱ级湿疹性皮炎,从而中断尼妥珠单抗治疗。16例作近期疗效评价,其中PR4例,SD10例,PD2例。6个月无进展生存率和总生存率分别为72.1%和86.3%。其中3例发生肿瘤假性进展。结论：本研究初步显示尼妥珠单抗联合放疗加同期替莫唑胺治疗HGG不良反应较小,患者可以耐受,近期疗效较好,远期疗效尚需进一步观察。     

西妥昔单抗联合放化疗治疗进展期鼻咽癌的临床研究

背景与目的:最新研究报道,西妥昔单克隆抗体(单抗)联合放疗较单纯放疗降低了局部晚期头颈部鳞癌患者的死亡率.为探讨西妥昔单抗在鼻咽癌中的作用,本研究初步观察西妥昔单抗联合放化疗治疗晚期鼻咽癌患者的不良反应及近期疗效.方法:取我院收治的晚期鼻咽癌患者12例.西妥昔单抗与放疗或化疗或同步放化疗同时使用,用法:西妥昔单抗第1周初始剂量为400 mg/m2,以后每周维持剂量为250 mg/m2,共8周.初诊或局部复发鼻咽癌患者均采用调强放疗技术,给予鼻咽部GTV处方剂量D6 975 cGy/31次,6.2周完成.对鼻咽癌转移灶姑息放疗,予转移灶外照射D3 000 cGy/10次,2周完成.结果:2例放疗后多脏器转移患者因病情进展而停用西妥昔单抗,2例初诊鼻咽癌因西妥昔单抗引起的Ⅲ级舌黏膜反应而停药,2例因Ⅲ级皮疹延迟用药1周,余6例顺利完成治疗计划.西妥昔单抗主要不良反应为皮疹、甲沟炎、黏膜反应、疲乏等.10例鼻咽部调强放疗同时使用西妥昔单抗的患者中,5例出现Ⅲ级口咽黏膜反应,其中4例同时出现Ⅲ级舌黏膜反应.全组完全缓解7例(58.3%),部分缓解3例(25.0%),疾病稳定2例(16.7%).中位随访14个月,2例死亡,10例存活且肿瘤无进展.结论:西妥昔单抗联合放化疗治疗晚期鼻咽癌的安全有效,但联合鼻咽部调强放疗时少部分患者出现较重的舌黏膜反应,影响治疗计划的顺利进行,需进行进一步临床试验研究.     

尼妥珠单抗联合三维适形放疗及化疗治疗局部晚期鼻咽癌的初步临床研究

  目的   探讨尼妥珠单抗联合同期三维适形放疗(3D-CRT)及化疗治疗Ⅲ、ⅣA期鼻咽癌的疗效及不良反应。   方法  经组织病理确诊的Ⅲ、ⅣA期(2008分期)鼻咽癌初诊患者63例随机分为对照组(33例)和治疗组(30例), 均采用3D-CRT及同期和序贯紫杉醇顺铂方案化疗, 治疗组每周一放疗前行尼妥珠单抗100mg治疗, 共6~7次。   结果   放疗结束后2个月原发灶CR率、颈部淋巴结CR率治疗组分别为100.0%、96.7%, 明显高于对照组的81.8%及75.8%(P均 < 0.05), 放疗后1年局部控制率、无转移生存率在治疗组及对照组分别达到100.0%vs.89.3%、95.5%vs.82.1%(P > 0.05), 两组主要不良反应为放射性咽喉炎、放射性皮炎和恶心呕吐、白细胞减少、疲乏等, 耐受性较好。治疗组发生3度以上放射性咽喉炎(P < 0.05)、放射性皮炎(P > 0.05)较对照组偏高。   结论   尼妥珠单抗联合3D-CRT及紫杉醇及顺铂同期及序贯化疗治疗局部晚期鼻咽癌, 可提高近期完全缓解率及局部控制率, 耐受性较好, 远期生存率有待进一步观察研究。      

局部晚期鼻咽癌EGFR单抗诱导治疗疗效与EGFR表达的相关性

目的:通过对照研究，探讨局部晚期鼻咽癌患者的EGFR表达水平与联合EGFR单抗诱导治疗疗效的相关性。方法:118例来自“尼妥珠单抗、顺铂、5-氟尿嘧啶诱导化疗后顺铂同期调强放射治疗局部晚期鼻咽癌多中心前瞻性随机对照研究”的病例，通过免疫组化检测EGFR表达水平。其中，尼妥珠单抗联合顺铂、5-氟尿嘧啶方案诱导治疗组（NPF组）58例，多西他赛、顺铂、5-氟尿嘧啶方案诱导化疗组（TPF组）60例。比较两组EGFR表达情况与诱导治疗疗效相关性。结果:全组EGFR表达率为94.9%；EGFR表达与性别、临床分期等临床特征无显著相关（P>0.05）。EGFR表达水平与TPF诱导化疗的疗效无显著相关（P=0.090），但显著影响联合尼妥珠单抗的诱导治疗疗效(P=0.015)；与TPF化疗比较，EGFR高表达水平患者接受联合EGFR单抗的诱导治疗有更好的治疗反应（P=0.033）。结论:在局部晚期鼻咽癌中，EGFR的表达水平与联合EGFR单抗诱导治疗的疗效密切相关；对于EGFR高水平表达的患者，增加EGFR单抗可能提高诱导治疗的临床获益。     

尼妥珠单抗联合DCF方案治疗晚期胃癌的临床观察

目的 观察尼妥珠单抗联合DCF方案治疗晚期胃癌的近期疗效及不良反应。方法 36 例晚期胃癌患者分为治疗组和对照组。治疗组（n =17）采用尼妥珠单抗联合DCF方案治疗：尼妥珠单抗200mg,每周1 次,连用6 个周期,之后同剂量每2 周1 次进行巩固治疗,至病情进展停用;多西他赛60mg/m2,静脉滴注,dl;顺铂60mg/m2,静脉滴注,dl;氟尿嘧啶600mg/m2,持续静脉输注120h。对照组（n=19）仅用DCF 方案治疗,同治疗组。结果 36 例患者均可进行评价。治疗组有效率（RR）为64.8 %,疾病控制率（DCR）为82.4%;对照组RR为31.6%,DCR为47.4％。两组间RR、DCR 比较差异均有统计学意义（P＜0.05）。治疗组与对照组主要的毒副反应有疲乏、白细胞减少、恶心呕吐、脱发等,两组间比较差异无统计学意义（P＞0.05）。结论 尼妥珠单抗联合DCF 方案治疗晚期胃癌安全有效,值得进一步扩大样本研究。     

Phase I and pharmacokinetic study of S-1 combined with weekly paclitaxel in patients with advanced gastric cancer

OBJECTIVE: A dose-escalation study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the dose-limiting toxicities (DLTs) in advanced gastric cancer. PATIENTS AND METHODS: Twelve patients were enrolled. S-1 was given orally at a fixed dosage of 40 mg/m(2) b.i.d. for 14 consecutive days, followed by a 1-week rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8 at a dose of 50, 60, 70 or 80 mg/m(2), depending on the DLTs. Treatment was repeated every 3 weeks. A pharmacokinetic study was conducted in an additional 5 patients on days 7 and 8 during the first course given at the RD. RESULTS: The MTD of paclitaxel was presumed to be 60 mg/m(2), because 50.0% of patients (2/4) developed DLTs (mainly grade 3 anorexia). DLT was observed in 1 out of 8 patients at a dose of 50 mg/m(2). Therefore, the RD of paclitaxel was estimated to be 50 mg/m(2). The preliminary response rate was 62.5% (5/8) at the RD. There were no significant pharmacokinetic interactions between S-1 and paclitaxel. An adequate plasma paclitaxel concentration for an antineoplastic effect was achieved with weekly doses of 50 mg/m(2). CONCLUSION: Weekly paclitaxel combined with S-1 was demonstrated to exhibit a tolerable toxicity profile with therapeutic plasma concentration at the dose of 50 mg/m(2). This regimen could represent a novel and low toxic combination for advanced gastric cancer.     

尼妥珠单抗联合化疗治疗恶性胶质瘤

目的 评价尼妥珠单抗联合化疗治疗恶性胶质瘤的疗效及不良反应.方法 尼妥珠单抗200 mg/次,每周1次,连续8周后改为每2周1次;根据患者O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)蛋白表达状况和既往化疗效果,采用个体化的化疗方案.结果 14例恶性胶质瘤患者共接受尼妥珠单抗治疗122次,中位治疗7.5次(2～20次).联合的化疗方案中,替莫唑胺21 d方案10例,替莫唑胺5 d力案2例,替尼泊甙联合顺铂方案1例,替尼泊甙联合尼莫司汀方案1例.PR 3例(21.4%),SD 6例(42.9%),客观有效率为21.4%,疾病控制率(PR+SD)为64.3%.中位无进展生存期(PFS)为4个月(95%CI0.7～7.3),6个月的疾病无进展生存率为30.6%.主要的不良反应为Ⅰ～Ⅱ度的中性粒细胞下降(2例)、血小板下降(2例)、淋巴细胞下降(1例)、恶心呕吐(3例)和无症状的转氨,升高(1例).1例替尼泊甙联合顺铂方案化疗的患者发生Ⅳ度中性粒细胞下降和血小板下降.1例患者出现尼妥珠单抗治疗相关痤疮样皮疹.结论 尼妥珠单抗联合化疗治疗恶性胶质瘤有一定疗效,患者耐受性好,值得进一步扩大病例数开展临床研究.

Abstract：

Objective Nimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas. Methods The patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred.Individualized chemotherapy was administered based on O6-methylguanine-DNA methyltransferase (MGMT)expression and previous chemotherapy responses in combined with nimotuzumab. Results Fourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 ( median 7.5 times ). Combined chemotherapy regimens included:continuous 21-day temozolomide ( 10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin ( 1 case), and teniposide plus nimustine ( 1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively.Disease control rate ( PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI:0.7-7.3) and PFS at 6 months was 30. 6%. The most common toxicities include grade Ⅰ -Ⅱ neutropenia (2 cases), thrombocytopenia ( 2 cases), lymphopenia ( 1 case), nausea and vomitting ( 3case) and asymptomatic transaminase increase ( 1 case). One patient developed grade Ⅳ neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash. Conclusions Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.     

尼妥珠单抗联合同期放化疗局部晚期NSCLC的Ⅰ期耐受性研究

目的 探索尼妥珠单抗与同期放化疗联合应用在Ⅲ期NSCLC的可行性与耐受性。方法 选取 18~74岁Ⅲ_A、Ⅲ_B期NSCLC初治患者。尼妥珠单抗分为100、200、400 mg组,每组 3~6例。前 3例如出现 1例剂量限制性毒性(DLT)则再增加 3例,半数出现DLT则停止爬坡。放疗总剂量 60~66 Gy分 30~33次。采用顺铂、依托泊苷联合化疗。同步结束后继续尼妥珠单抗至16周或进展,加或不加同方案化疗2周期。评价不良反应、近期疗效、最佳肿瘤体积退缩情况及生存情况。结果 共入组 9例,7例可检测EGFR表达。3个剂量组均能良好耐受,未有DLT发生。最常见不良反应为血液系统, 3级白细胞减少、粒细胞减少、血红蛋白降低及血小板减少分别为66%、66%、11%、22%;其次为食管炎, 1级44%、2级22%;1级恶心呕吐44%;1级放射性肺炎44%。未发现皮疹或皮肤过敏反应。最佳总体积退缩平均为88%。中位随访时间和中位生存时间26.4个月,1年和 2年OS、DFS、PFS分别为78%和67%、56%和44%、78%和56%。结论 尼妥珠单抗100、200、400 mg每周方案与同期放化疗应用在局部晚期NSCLC可被良好耐受。     

Nimotuzumab plus paclitaxel and cisplatin as the first line treatment for advanced esophageal squamous cell cancer: A single centre prospective phase II trial

Nimotuzumab (N) is a humanized anti‐epidermal growth factor receptor monoclonal antibody. This prospective, single‐armed, open label phase II study was conducted to evaluate the efficacy and safety of the combination of paclitaxel (T)/cisplatin (P) with nimotuzumab (N) as first‐line treatment in advanced esophageal squamous cell carcinoma (ESCC). Patients with pathologic confirmed unresectable locally advanced or metastatic ESCC were treated with the TPN regimen: nimotuzumab 200 mg weekly, paclitaxel 175 mg/m² on day 1 and cisplatin 30 mg/m² on days 1 and 2; repeat cycle every 3 weeks for six cycles. Radiotherapy was allowed to be admitted after four cycles of TPN treatment. The primary endpoint was the objective response rate (ORR). The secondary endpoint was the overall survival (OS), duration of disease control (DDC) and toxicities. From March 2011 to April 2013, a total of 59 patients were enrolled and 56 were eligible for the final analysis. Overall RR was 51.8% and disease control rate (DCR) (CR + PR + SD) was 92.9%. Local treatment (radiotherapy or surgery) followed by chemotherapy improved the duration of disease control for patients with metastatic disease and local‐regional advanced disease to 8.2 months and more than 23 months, respectively. The OS for patients with metastatic disease was 14.0 months (95% CI: 6.8–21.2 months). The most common G3/4 toxicities were neutropenia (46.4%), nausea (48.3%), alopecia (78.6%), anorexia (42.8%), vomiting (55.4%), arthralgia (62.5%) and anorexia (5%). Adding nimotuzumab to the standard TP regiment was safe, and well tolerated. The TPN regimen is an effective combination as the first‐line chemotherapy for the patients with advanced ESCC, and appears more active than current standard regimens.     

Phase I studies of porfiromycin (NSC--56410) in solid tumors.

Porfiromycin was given to a group of patients with a variety of solid tumors. Of 114 patients admitted to the study, 103 yielded evaluable data. The following dosage schedules were used to determine the toxicity of porfiromycin when given in multiple doses by intravenous injection: 0.2 mg/kg x 5 days, 0.3 mg/kg x 5 days, 0.35 mg/kg x 5 days, 0.4 mg/kg x 5 days, 0.24 mg/kg x 10 days and 0.6 mg/kg weekly. Toxic effects noted were mainly leukopenia, thrombocytopenia, and, when injected paravenously, local tissue necrosis. Biological effects were noted at all dosage levels and were more severe at the higher dosages. The data suggest that profiromycin administered intravenously at a dose of 0.35 mg/kg daily for 5 days results in moderate hermatological toxicity and clinical evaluation in a Phase II study at this dosage level is indicated.     

Phase I study of weekly liposome-encapsulated doxorubicin in patients with advanced, androgen-independent prostate cancer

We performed a phase I study to evaluate the tolerability and activity of liposome-encapsulated doxorubicin (LED) given intravenously on a weekly basis in patients with advanced, androgen-independent prostate cancer. Nine patients were accrued to three dose levels: 10, 15, and 20 mg/m2. Treatment was administered weekly for 4 weeks out of a 6-week cycle. Two instances of grade II neutropenia were observed at the two higher dose levels. No dose adjustments were required. There were no severe hematologic or nonhematologic toxicities. Based on data from contemporaneous single-agent trials with this drug, we did not dose-escalate beyond 20 mg/m2. Six patients were removed from the study due to progressive disease by 6 weeks; the remaining 3 patients progressed by 12 weeks. These results suggest that LED is well tolerated at doses up to 20 mg/m2 when given weekly for 4 weeks out of a 6 week cycle. No clinical responses were seen; however, a phase II study of 20 mg/m2 is warranted to further delineate the activity of this regimen in patients with advanced prostate cancer.     

Nimotuzumab in combination with radiotherapy in high grade glioma patients: A single institution experience

Nimotuzumab, a humanized antibody targeting epidermal growth factor receptor, has potent anti-proliferative, anti-angiogenic, and pro-apoptotic effects in vitro and in vivo. It also reduces the number of radio-resistant CD133⁺ glioma stem cells. The antibody has been extensively evaluated in patients with advanced head and neck, glioma, lung, esophageal, pancreatic, and gastric cancer. In this single institution experience, 35 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with irradiation and 200 mg doses of nimotuzumab. The first 6 doses were administered weekly, together with radiotherapy, and then treatment continued every 21 days until 1 year. The median number of doses was 12, and the median cumulative dose was thus 2400 mg of nimotuzumab. The most frequent treatment-related toxicities were increase in liver function tests, fever, nausea, anorexia, asthenia, dizziness, and tremors. These adverse reactions were classified as mild and moderate. The median survival time was 12.4 mo or 27.0 mo for patients with GBM or AA patients, respectively, who received curative-intent radiotherapy in combination with the antibody. The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy. We have thus confirmed that nimotuzumab is a very well-tolerated drug, lacking cumulative toxicity after maintenance doses. This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients.     

Cyclophosphamide plus 5-FU versus 5-FU alone in advanced gastric carcinoma

30 patients with advanced metastatic gastric adenocarcinoma, having a measurable indicator lesion, were randomized (1:2) to receive (intravenously) either weekly 5-fluorouracil alone (15 mg/kg) or combination treatment with cyclophosphamide (20 mg/kg) given on day 1 and 5-FU (15 mg/kg) given weekly on weeks 2-5, beginning on day 8. The combination cycle was repeated at 6-week intervals. Although the toxic effects of therapy were similar in both arms, the addition of cyclophosphamide to the single-agent 5-FU regimen did not increase either the frequency of objective response (5-FU 18%, combination 16%) or improve the median survival of patients with advanced measurable gastric carcinoma (5-FU 4.4 months, combination 5.2 months). Patients with pretreatment weight loss greater than 10% had significantly (p less than 0.05) shorter median survival (2.8 versus 5.6 months) compared to patients without weight loss.     

Multicenter phase II trial of brequinar sodium in patients with advanced melanoma.

Seventeen patients with advanced melanoma and no prior exposure to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given at a median weekly dose of 1200 mg/m2 intravenously. In 14 patients evaluable for efficacy, there were no objective responses. The toxicity was moderate. We conclude that, at this dose and schedule, brequinar has no activity in advanced melanoma.