ABV方案化疗对艾滋病相关晚期卡波氏肉瘤外周血CD4淋巴细胞的影响

Objective: The combination of highly active antiretroviral therapy (HAART) and chemotherapy with ABV regimen (doxorubicin, bleomycin and vincristine) is a promising approach for the treatment of advanced HIV-related Kaposi’s sarcoma (KS). Here we analyzed the relationship between the CD4 lymphocyte cell count and the clinical response to chemotherapy. Methods: The 176 HIV infected patients with advanced KS who failed to respond to prior HAART were selected. All these patients were then preceded to chemother...     

８例经典型卡波氏肉瘤放疗加生物治疗的临床分析

目的　通过总结经典型卡波氏肉瘤（ＫＳ）的临床诊治经验,了解放疗加生物治疗的疗效。方法　回顾性分析８例经典型ＫＳ患者,对其临床表现、肿瘤特征、治疗方式、疗效和生存情况进行分析总结。８例均为少数民族,维吾尔族７例,哈萨克族ｌ例。放射治疗采用直线加速器６ＭＶＸ线,常规分割照射,每周５次,每次２００ｃＧｙ,总量３０～５０Ｇｙ。同时配合使用生物治疗：干扰素３００万单位,每天１次,２周;胸腺肽１.６ｍｇ,隔日１次,４周。结果　经典型ＫＳ主要发生在皮肤,常呈多发性,最常累及四肢远端,较少发生远处转移。８例患者的完全缓解率７５.０％,部分缓解率２５.０％,有效率１００％。结论　经典型ＫＳ是少见的软组织恶性肿瘤,新疆地区少数民族常见。放射治疗配合生物治疗是治疗经典型ＫＳ安全有效的方法,剂量以４０Ｇｙ左右为宜。     

食管癌患者化疗前后ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞及Ｆｏｘｐ３ｍＲＮＡ的表达及其临床意义

目的：探讨晚期食管癌患者化疗前后外周血中ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞及Ｆｏｘｐ３ｍＲＮＡ的表达变化及其临床意义。方法：采用流式细胞术检测６８例晚期食管癌患者化疗前后外周血ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞的水平,并与４０例健康成人进行比较。同时运用ＲＴ-ＰＣＲ方法检测其中４０例患者化疗前后外周血调节性Ｔ细胞Ｆｏｘｐ３基因ｍＲＮＡ的表达情况。结果：（１）食管癌患者外周血中ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞占ＣＤ４＋Ｔ细胞总数的（１.８２±０.５４）％,显著高于健康对照组的（１.５２±０.７０）％（Ｐ＜０.０１）;（２）化疗前患者外周血中ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞为（１.８２±０.５４）％,明显高于化疗后的（１.６６±０.５８）％（Ｐ＜０.０5）;（３）化疗前患者调节性Ｔ细胞Ｆｏｘｐ３基因ｍＲＮＡ的相对表达量为０.３１８±０.０２７,明显高于化疗后的０.２６６±０.０２８（Ｐ＜０.０５）。结论：食管癌患者接受化疗后外周血中Ｆｏｘｐ３ｍＲＮＡ水平与ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞数量表达均显著下降,推测Ｆｏｘｐ３基因可能对ＣＤ４＋ＣＤ２５ｈｉｇｈＴ细胞有重要的调节功能,从而影响食管癌患者化疗后ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞的水平。     

14—3—3β基因对卡波氏肉瘤细胞迁移作用的影响

目的：探讨14—3—3β基因（酪氨酸3-加单氧矽色氨酸5-加单氧酶激活蛋白基因）对卡波氏肉瘤（Kaposigsarcoma,KS）细胞迁移的影响。方法：采用脂质体法将14—3—3β基因稳定转染入BCBL—1（HHV-8 positiveand EBV negative human B cells）细胞,Western—Blot检测14—3—3β蛋白的表达,最后利用Transwell法分析14—3—3β基因对BCBL-1细胞迁移的影响（设立空载体组和阴性对照组）。结果：pcDNA3．1／myc—His（-）A-14—3—3β组细胞迁移数目明显高于pcDNA3．1／myc—His（-）A组和阴性对照组,差异具有统计学意义（P〈0．05）;pcDNA3．1／myc—His（-）A组和阴性对照组细胞迁移数目相比差异无统计学意义（P〉0．05）。结论：14—3—3β基因能促进KS细胞的迁移。     

14-3-3β基因对卡波氏肉瘤细胞迁移作用的影响

目的:探讨14-3-3β基因(酪氨酸3-加单氧酶/色氨酸5-加单氧酶激活蛋白基因)对卡波氏肉瘤(Kaposi's sarcoma,KS)细胞迁移的影响.方法:采用脂质体法将14-3-3β基因稳定转染入 BCBL-1(HHV-8 positive and EBV negative human B cells)细胞,Western-Blot检测14-3-3β蛋白的表达,最后利用Transwell法分析14-3-3β基因对BCBL-1细胞迁移的影响(设立空载体组和阴性对照组).结果:pcDNA3.1/myc-His(-)A-14-3-3β组细胞迁移数目明显高于pcDNA3.1/myc-His(-)A组和阴性对照组,差异具有统计学意义(P＜0.05);pcDNA3.1/myc-His(-)A组和阴性对照组细胞迁移数目相比差异无统计学意义(P＞0.05).结论:14-3-3β基因能促进KS细胞的迁移.     

利托那韦对卡波氏肉瘤相关疱疹病毒感染细胞LYN表达的影响北大核心CSCD

目的探讨蛋白酶抑制剂利托那韦对卡波氏肉瘤相关疱疹病毒(Kaposi’s sarcoma associated herpesvirus,KSHV)感染细胞LYN表达的影响。方法原代培养人脐静脉内皮细胞HUVECs,从BCBL-1中提取KSHV病毒感染HUVECs,PCR扩增KS330233证实感染成功。CCK8法测定半数抑制浓度,CCK8法检测细胞增殖能力,Western blot检测LYN表达及p-PI3K和p-AKT水平。结果 RTV作用于细胞的IC_(50)为25μmol/L。RTV与LYN抑制剂PP2能抑制KSHV感染的HUVECs的增殖和LYN、p-PI3K和p-AKT的表达(P<0.05)。结论 RTV可通过抑制LYN及其下游的PI3K/AKT信号通路抑制KSHV感染细胞HUVECs的增殖。     

参芪扶正注射液联合化疗对乳腺癌Ｔ淋巴细胞Ａｇ-ＮＯＲｓ的影响

目的：探讨参芪扶正注射液对乳腺癌化疗患者免疫功能指标Ｔ淋巴细胞Ａｇ-ＮＯＲｓ、生活质量及毒副反应的影响。方法：选择经病理组织学证实的晚期乳腺癌患者６３例,分为治疗组３２例和对照组３１例,化疗方案都采用长春瑞滨（ＮＶＢ）联合顺铂（ＤＤＰ）,治疗组加用参芪扶正注射液,对照组单纯应用化疗,进行对比观察。结果：治疗组治疗后免疫功能指标上升,生活质量改善率高,化疗毒副反应低,与对照组比较有明显差异（Ｐ＜０.０１）。结论：参芪扶正注射液对乳腺癌化疗患者能明显改善患者的免疫功能,降低化疗的毒副反应,提高生活质量。     

外周血T淋巴细胞亚群与接受卡瑞利珠单抗治疗的晚期非小细胞肺癌患者预后的关系

目的 探索外周血T淋巴细胞亚群与接受卡瑞利珠单抗治疗的晚期非小细胞肺癌（NSCLC）患者预后的关系。方法 回顾性收集接受卡瑞利珠单抗治疗的88例晚期NSCLC患者资料。分别收集患者治疗前和治疗后2个月的外周血淋巴细胞亚群相对计数,使用Kaplan-Meier曲线和Cox回归分析研究外周血T淋巴细胞亚群与PFS和OS之间的关系。结果 有反应组患者治疗前外周血CD4+/CD8+比值高于无反应组（P=0.038）,而CD8+T淋巴细胞百分比低于无反应组（P=0.036）;生存分析显示治疗前CD4+/CD8+比值越高,患者PFS和OS越长（P=0.001,P=0.023）。多变量Cox分析显示,治疗前CD4+/CD8+比值是预测PFS和OS的因素。此外,治疗后CD4+/CD8+比值、CD4+T淋巴细胞百分比越高,患者PFS越长（P=0.005,0.015）;CD8+T淋巴细胞百分比越低,患者PFS和OS越长（P=0.001,P=0.016）。结论 外周血CD4+/CD8+比值能够预测接受卡瑞利珠单抗治疗的NSCLC患者的生存情况。     

PFC方案化疗对进展期胃癌患者外周血淋巴细胞表型的影响

目的探讨紫杉醇(paclitaxel)联合氟尿嘧啶(5-Fu)及顺铂(CDDP)的治疗方案(简称PFC方案)对进展期胃癌患者外周血淋巴细胞表型的影响.方法 47例经病理学或细胞学确诊的进展期胃癌患者,采用PFC方案化疗(紫杉醇50 mg/m2,静滴3 h, 第1,8,15天;5-Fu 750 mg/m2,用便携式微量输液泵持续静脉输注,第1～5天;CDDP 20 mg/m2,静滴,第1～5天;每4周重复).应用流式细胞仪检测CD3 、CD4 、CD8 、CD16 56 、CD19 细胞的百分率.结果进展期胃癌患者经PFC方案化疗后CD4 、CD4 /CD8 、CD16 56 较化疗前显著升高(P＜0.05);CD3 、CD8 、CD19 化疗前后差异无显著性(P＞0.05).结论 PFC方案化疗可改善进展期胃癌患者机体的免疫功能.     

氩氦冷冻消融对晚期肾癌外周血调节性T 细胞的影响*

目的：研究氩氦冷冻消融治疗对晚期肾癌患者外周血CD4 +CD 25+ 调节性T 细胞（Treg ）的影响及临床意义。方法：回顾性分析本院32例晚期肾癌患者临床资料,所有患者均于氩氦冷冻消融治疗术前、术后1～6 个月分别取外周血,应用流式细胞仪检测外周血T 淋巴细胞亚群（CD3 + T、CD4 + T、CD8 + T、CD4 +T/CD 8 +T、NK细胞、Treg 细胞）变化情况。术后1 个月采用增强MRI或CT评价肿瘤坏死情况,影像学显示肿瘤无强化区即认为肿瘤坏死,根据Cavalieri 方法计算肿瘤坏死率,进而评价肿瘤负荷。结果：冷冻消融治疗术后,Treg 细胞比例由术前（4.18± 1.58）% 逐渐下降至第3 个月达最低值（1.96± 0.54）% ,二者差异有统计学意义（P=0.001）。 CD3 +T、CD4 +T、CD4 +T/CD 8 +T、NK细胞比例分别由术前（19.26± 7.52）% 、（43.54± 12.99）% 、（1.15± 0.57）% 、（17.49±8.36）% 逐渐上升至第3 个月达最大值（30.83± 5.69）% 、（49.58± 10.76）% 、（1.84± 0.12）% 、（27.63± 8.20）% ,差异均有统计学意义（P=0.000,P=0.003,P=0.02,P=0.001）。 CD8 + T由术前（40.86± 8.89）% 逐渐下降至第3 个月达最低值（26.74± 4.29）% ,差异具有统计学意义（P=0.000）。 冷冻治疗后3～6 个月CD3 +T、CD4 +T、CD4 +T/CD 8 +T、NK、CD8 + T、Treg 细胞比例虽略有改变但差异均无统计学意义（P>0.05）。相关性分析结果表明：经氩氦冷冻治疗后Treg 细胞比例变化与肿瘤负荷下降程度呈正相关（r=0.793,P<0.01）。结论：肾癌氩氦冷冻治疗后外周血T 淋巴细胞亚群分布异常得到一定改善,抗肿瘤免疫反应增强,Treg 细胞比例变化与肿瘤负荷有关。     

Plasma biomarkers of clinical response during chemotherapy plus combination antiretroviral therapy (cART) in HIV+ patients with advanced Kaposi sarcoma

This study aimed to evaluate plasma concentration of selected cancer-associated inflammatory and immune-modulated cytokines in HIV+ patients with advanced Kaposi sarcoma (KS), and to explore candidate biomarkers capable of predicting clinical outcome in response to chemotherapy (CT) plus combination antiretroviral therapy (cART).Thirty-seven plasma cytokines/chemokines were assessed by Luminex technology in 27 consecutive HIV+ KS patients, followed-up during CT and cART of maintanence (m-cART). Associations between plasma concentration of biomarkers and patient clinical response to m-cART were evaluated by means of Hazard Ratios (HRs) and corresponding 95% Confidence Intervals (CIs).Plasma baseline concentration of Granulocyte colony-stimulating factor (G-CSF), Hepatocyte growth factor (HGF) and endoglin were found to be associated with m-cART clinical response (HR:1.56, 95%CI:1.09–2.22, p = 0.01; HR:0.32, 95% CI:0.10–0.99, p = 0.05; HR:0.72, 95% CI:0.54–0.96, p = 0.03, respectively). The multivariate analysis confirmed the associations of baseline plasma G-CSF and HGF concentration with m-cART clinical complete remission response (HR:1.78, 95% CI:1.15–2.74, p = 0.009; HR:0.19, 95% CI:0.04–0.95, p = 0.04).Our exploratory study suggested that plasma G-CSF, HGF and endoglin may be novel predictors of clinical response during m-cART in HIV+ KS patients. Nonetheless, these findings should be further validated in an independent population study.     

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Between 1984 and 2006, 12 959 people with HIV/AIDS (PWHA) in the Swiss HIV Cohort Study contributed a total of 73 412 person-years (py) of follow-up, 35 551 of which derived from PWHA treated with highly active antiretroviral therapy (HAART). Five hundred and ninety-seven incident Kaposi sarcoma (KS) cases were identified of whom 52 were among HAART users. Cox regression was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI). Kaposi sarcoma incidence fell abruptly in 1996-1998 to reach a plateau at 1.4 per 1000 py afterwards. Men having sex with men and birth in Africa or the Middle East were associated with KS in both non-users and users of HAART but the risk pattern by CD4 cell count differed. Only very low CD4 cell count (<50 cells microl(-1)) at enrollment or at HAART initiation were significantly associated with KS among HAART users. The HR for KS declined steeply in the first months after HAART initiation and continued to be low 7-10 years afterwards (HR, 0.06; 95% CI, 0.02-0.17). Thirty-three out of 52 (63.5%) KS cases among HAART users arose among PWHA who had stopped treatment or used HAART for less than 6 months.     

改良MAID方案治疗54例晚期软组织肉瘤的疗效分析

背景与目的:临床研究表明MAID方案连续静脉输注72h治疗晚期软组织肉瘤的近期疗效较以阿霉素(ADR)为主的二药联合方案疗效高,肿瘤无进展时间长,但是对患者长期生存无明显改善,严重的Ⅲ/Ⅳ度血液学毒性和治疗相关死亡影响了其在临床广泛使用。本研究通过用四氢吡喃阿霉素(THP-ADR)替代MAID方案中的ADR和改良异环磷酰胺(IFO)用法治疗晚期软组织肉瘤,观察改良方案的疗效和不良反应。方法:通过多中心协作筛选符合标准的患者接受IFO2000mg/m2静脉滴注4hd1～3,美斯钠1200mg/m2在IFO治疗的0、4和8h静脉滴注d1～3,THP-ADR20mg/m2和达卡巴嗪(DTIC)333.3mg/m2持续静脉滴注d1～3,THP-ADR和DTIC溶于同一液体瓶或泵中通过中心静脉导管输注,每3周重复,至少2周期,评定近期疗效和毒性反应。对所有完成2周期治疗的患者每2月随访1次,直至随访截止。利用寿命表法计算长期生存率和肿瘤进展时间。结果:可评价的54例患者全部完成至少2周期改良MAID方案化疗,总有效率42.59%。不良反应较轻,Ⅲ Ⅳ度中性粒细胞减少发生率25.93%,粒细胞减少性发热11.11%,Ⅲ Ⅳ度血小板减少发生率16.67%,其它毒性少见,无明显的肝肾毒性、无治疗相关性死亡和中枢神经系统毒性反应。随访2年,至肿瘤进展时间为7个月,1年和2年生存率分别为61.11%和36.36%。结论:改良MAID方案简化了原方案中三种药物均需要同时连续输注的过程,有比较好的有效率和长期生存,未见严重毒性反应,耐受性良好,值得进一步前瞻性随机对照研究。     

KSHV genotypes A and C are more frequent in Kaposi sarcoma lesions from Brazilian patients with and without HIV infection,respectively

The present study aimed to evaluate the frequency of KSHV genotypes isolated from Kaposi sarcoma (KS) lesions in patients from Brazil. Fifty KS cases were evaluated. The most frequently detected viral genotypes were A (50.0%) and C (48.0%); the B genotype was isolated only in one case (2.0%). Noteworthy, there was a significant predominance of A genotypes in KS lesions from HIV-positive patients, whereas C genotypes were found mostly in the HIV-negative setting. This finding supports the hypothesis that distinct KSHV genotypes have a non-random distribution in KS, which might be attributable to unique biological properties.     

Pegylated liposomal doxorubicin as second-line therapy in the treatment of patients with advanced classic Kaposi sarcoma: a retrospective study

BACKGROUND: Classic Kaposi sarcoma (CKS) is a rare neoplasm that predominantly occurs in elderly subjects and has a variable clinical evolution. The clinical course is usually indolent, but occasionally the neoplasm progresses rapidly and spreads to internal organs, necessitating systemic chemotherapy. Because of the rarity of CKS, the best treatment has not been determined to date. To the authors' knowledge, few data exist regarding the use of pegylated liposomal doxorubicin (PLD) as first-line and second-line treatment in advanced CKS. The current retrospective study investigated the activity and toxicity of PLD in pretreated patients with aggressive, nonvisceral CKS. METHODS: Patients were treated with PLD at a dose of 20 mg/m(2) intravenously every 3 weeks until disease progression or the occurrence of intolerable side effects. Objective responses were determined after 3 and 6 cycles; toxicity was assessed every cycle. Secondary endpoints were pain intensity, progression-free survival, and overall survival. RESULTS: Twenty men with pretreated CKS (median age, 67 years) were treated with PLD. All patients received at least 6 cycles of therapy. Complete and partial responses were observed in 2 patients (10%) and 14 patients (70%), respectively. Neutropenia was the most significant grade 3 hematologic toxicity observed (evaluated according to the National Cancer Institute Common Toxicity Criteria for Adverse Events [version 3.0]), occurring in 20% of patients. Only 1 patient (5%) demonstrated grade 4 neutropenia. Fourteen patients (70%) achieved remission of pain and/or edema after 6 cycles. The median progression-free survival was 9 months (95% confidence interval, 5-13 months). At a median follow-up of 36 months, 15 patients (75%) remained alive. CONCLUSIONS: PLD is associated with an improvement in objective response and pain intensity and is well tolerated as a second-line treatment for CKS.     

Pharmacokinetics of low-dose doxorubicin and metabolites in patients with AIDS-related Kaposi sarcoma

Purpose Systemic chemotherapy is the treatment of choice for AIDS-related advanced Kaposi sarcoma. One principal schedule combines adriamycin (doxorubicin), bleomycin, and vincristine (ABV). We analysed the plasma concentrations of low-dose doxorubicin (Dx) and its metabolites doxorubicinol, 7-deoxydoxorubicinone, doxorubicinone, doxorubicinolone, and 7-deoxydoxorubicinolone in AIDS-patients to define patient-group and dose-specific pharmacokinetic parameters.Materials and methods A previously described high-performance liquid chromatographic (HPLC) method and a population approach with non-linear mixed effects modelling (NONMEM) were used for analysis and subsequent modelling of the time–concentration data of low-dose Dx and metabolites in seven patients with AIDS-related advanced Kaposi sarcoma. Patients received Dx 20 mg m^–2, bleomycin 15 U m^–2 and vincristine 2 mg as a 30-min intravenous infusion each. Blood samples were collected up to 72 h after the start of Dx treatment. WinNonlin software version 4.1 was used for non-compartmental analysis and NONMEM software version V for compartmental analysis. Covariate analysis was performed for various clinical and laboratory parameters.Results Non-compartmental analysis yielded an area under the plasma concentration–time curve (AUC) for Dx of 566 g h L^–1, a maximum plasma concentration (c_max) of 599 g L^–1 and an elimination half-life (t_1/2) of 30.8 h. Compartmental analysis resulted in a two-compartment model with first-order elimination, which best fitted the concentration–time data. Model estimate for Dx clearance was 61.8 L h^–1, for intercompartmental clearance (Q) 112 L h^–1, for the volume of the central compartment (V₁) 23.3 L, and for the volume of the peripheral compartment (V₂) 1,130 L. Metabolite data could adequately be estimated by NONMEM using single-compartment models. Graphical plots of residuals versus time for all metabolites yielded no evidence of non-linear pharmacokinetic behaviour. Laboratory parameters of liver and renal function were all in the normal range and their inclusion in the pharmacokinetic model did not improve data fit. A final jack-knife analysis was performed.Conclusions Concentration–time data for low-dose Dx and metabolites in the ABV-regimen are best described by a two-compartment model with first-order elimination. The results confirm that the aglycones doxorubicinone, 7-deoxydoxorubicinone, and doxorubicinolone can be reliably detected in the studied patient group and implemented into a common metabolic model. Model estimates suggest that pharmacokinetic parameters are similar for low-dose Dx and higher-dosed Dx. As the role of the aglycones is still poorly understood, despite their potential clinical relevance, their analysis should be implemented in future pharmacokinetic and pharmacodynamic studies of Dx.     

Phase 1/2 trial of BMS-275291 in patients with human immunodeficiency virus-related Kaposi sarcoma: a multicenter trial of the AIDS Malignancy Consortium

BACKGROUND: Matrix metalloproteinases (MMPs) are overexpressed in Kaposi sarcoma (KS). The safety and efficacy of a novel, orally bioavailable MMP inhibitor, BMS-275291, was evaluated in patients with human immunodeficiency virus-associated KS and the correlation between changes in the percentage of apoptotic cells in tumor biopsies and response was explored. METHODS: Cohorts of 6 patients were to be treated with BMS-275291. The initial cohort received 1200 mg once a day; subsequent doses were to be escalated to 600 mg twice daily and 1200 mg twice daily, or decreased to 600 mg/day. Tumor biopsies for apoptosis assays were collected pretreatment and on Day 29. Prospectively defined dose level adjustments were to be based on dose-limiting toxicity (DLT), tolerability, changes in the percentage of apoptotic cells, and treatment response. RESULTS: Sixteen patients were enrolled; 15 received the study drug and could be evaluated. The median duration of treatment was 20 weeks (range, 3-54 weeks). A dose of 1200 mg once a day was well tolerated but induced only 1 response. A DLT occurred in 3 patients treated with 600 mg twice daily, and included grade 3 fatigue, grade 3 allergic reaction, and grade 3 arthralgias; 2 responses were noted at this dose level (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Based on predetermined endpoints, the trial was closed after accrual of 15 treated patients. Assessment of biologic response for dose escalation/de-escalation decisions utilizing the apoptosis assay was not feasible. CONCLUSIONS: BMS-275291 given at a dose of 600 mg twice daily induced unacceptable toxicity. The better-tolerated schedule of 1200 mg once a day demonstrated inadequate efficacy in patients with human immunodeficiency virus-associated KS. The apoptosis assay was not helpful in predicting response.     

Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma

The effect of highly active antiretroviral therapy (HAART) on survival in HIV-infected patients with Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL) is unknown. Our study examines survival after HAART for these 2 malignancies. Analyses were performed using data from 387 HIV-infected men in the Multicenter AIDS Cohort Study (MACS) after a diagnosis of either KS or NHL in 1990-99. Potential prognostic factors, including HAART, were evaluated in univariate analyses using Kaplan-Meier survival curves and log-rank tests. Multivariate survival analyses were conducted using Cox's time-dependent proportional hazards models, adjusting for CD4(+) cell levels at the time of cancer diagnosis and other covariates. Forty-three of 287 KS patients (15%) and 13 of 100 NHL patients (13%) had been treated with HAART. HAART treatment was associated with improved survival for KS and NHL patients (log-rank p = 0.0001 for each group). In multivariate analyses, HAART was associated with an 81% reduced risk of death among KS patients [relative hazard (RH) 0.19, 95% confidence limits (CL) (0.08, 0.45)], compared to those not exposed to HAART and an 84% reduced risk [RH 0.16, 95% CL (0.04, 0.64)] among NHL patients. Relative hazards estimates were similar for those with HAART initiation before and after NHL diagnosis. The use of HAART prolongs overall survival among HIV-positive men diagnosed with KS and NHL. HAART appears to be effective in improving survival even when initiated after the diagnosis of NHL and KS.     

Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus‐associated Kaposi sarcoma

BACKGROUND:

Paclitaxel and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency virus (HIV)‐associated Kaposi sarcoma (KS). A randomized trial comparing the efficacy and toxicity of paclitaxel and PLD was performed, and the effects of therapy on symptom palliation and quality of life were determined.

METHODS:

Patients with advanced HIV‐associated KS were randomly assigned to receive paclitaxel at a dose of 100 mg/m² intravenously (iv) every 2 weeks or PLD at a dose of 20 mg/m² iv every 3 weeks. The KS Functional Assessment of HIV (FAHI) quality of life instrument was used before and after every other treatment cycle.

RESULTS:

The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the paclitaxel arm and 37 in the PLD arm; 73% of patients received highly active antiretroviral therapy (HAART) and 32% had an undetectable viral load (<400 copies/mL). Treatment was associated with significant improvements in pain (P = .024) and swelling (P < .001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the paclitaxel and PLD arms revealed comparable response rates (56% vs 46%; P = .49), median progression‐free survival (17.5 months vs 12.2 months; P = .66), and 2‐year survival rates (79% vs 78%; P = .75), but somewhat more grade 3 to 5 toxicity for paclitaxel (84% vs 66%; P = .077).

CONCLUSIONS:

Treatment with either paclitaxel or PLD appears to produce significant improvements in pain and swelling in patients with advanced, symptomatic, HIV‐associated KS treated in the HAART era. Cancer 2010. © 2010 American Cancer Society.