依维莫司治疗复发难治性骨肉瘤与软组织肉瘤的疗效评估北大核心CSCD

目的：观察依维莫司治疗复发难治性骨肉瘤与软组织肉瘤的临床疗效和安全性。方法：这是一项回顾性研究。2014年1月-2015年8月收治的20例二线放化疗失败的复发难治性骨肉瘤与软组织肉瘤患者接受依维莫司治疗（10mg／次,1次／d,28d为1个治疗周期）;如患者发生不可耐受的不良反应,可减量至5rag／次,1次／d。评价依维莫司治疗的疗效和安全性。结果：20例患者中,骨肉瘤10例,软组织肉瘤10例（腺泡状软组织肉瘤2例、上皮样肉瘤2例、黏液纤维肉瘤1例、滑膜肉瘤1例、梭形细胞肉瘤1例、尤文肉瘤1例、恶性神经鞘瘤2例）。依维莫司治疗后,部分缓解5例,疾病稳定10例,疾病进展4例,疾病控制率为75％（15／20）。20例患者的中位无进展生存时间为46d（95％可信区间：29～63d）,中位生存时间为56d（95%可信区间：33～79d）。10例软组织肉瘤患者和10例骨肉瘤患者的中位无进展生存时间分别为35d和56d,中位生存时间分别为84d和140d。主要的不良反应包括口腔炎（80％）、胃肠反应（30％）、皮疹（25％）和乏力（25％）。结论：依维莫司治疗复发难治性骨肉瘤与软组织肉瘤可取得一定的疗效,不良反应较轻,耐受良好。     

依维莫司联合化疗或靶向药物治疗晚期非小细胞肺癌的临床疗效和安全性

目的:探索依维莫司联合化疗或靶向药物在二线及多线晚期非小细胞肺癌（non-small-cell lung cancer,NSCLC）中的疗效和安全性。方法:回顾性分析我院2014年1月至2015年12月25例IV期NSCLC患者,二线及多线治疗时应用依维莫司5mg/d联合化疗或靶向药物,观察临床疗效和不良反应。首要观察终点是3个月时的疾病控制率,次要观察指标是无进展生存期。结果:患者中部分缓解1例（4.8%）,疾病稳定14例（66.7%）,疾病进展6例（28.6%）,总体疾病控制率为71.4%,其中3个月时疾病稳定13例,3个月时疾病控制率62%;中位无进展生存期3.2个月。4例出现Ⅲ/Ⅳ级不良反应,表现为口腔黏膜炎、间质性肺炎和腹泻。结论:依维莫司联合化疗或靶向药物用于二线或多线治疗晚期NSCLC能够控制疾病进展,耐受性良好。     

多西紫杉醇联合卡培他滨治疗转移性乳腺癌30例

 【摘要】　目的　观察多西紫杉醇联合卡培他滨方案治疗转移性乳腺癌的临床疗效及患者不良反应。方法　30例转移性乳腺癌患者应用多西紫杉醇35 mg／m2,第1、8天静脉滴注1 h,卡培他滨1000 mg／m2,口服,早晚 2次餐后服用,连用14 d,21 d为 1个周期,至少应用 2个周期后评价疗效。每周期化疗前后复查血常规及生化指标。结果　30例患者中完全缓解（CR）1例,部分缓解（PR）15例,疾病稳定（SD）11例,疾病进展（PD）3例,总有效（CR+PR）率53.3 %;中位生存时间14个月,疾病进展时间8.5个月;不良反应主要有骨髓抑制、胃肠道反应、手足综合征,均可耐受。结论　多西紫杉醇联合卡培他滨方案治疗转移性乳腺癌疗效确切,患者不良反应可以耐受。     

培美曲塞联合顺铂治疗难治性转移性晚期乳腺癌23例

 目的　研究培美曲塞联合顺铂方案治疗难治性转移性乳腺癌的疗效和患者不良反应。方法　用培美曲塞联合顺铂方案治疗难治性转移性乳腺癌23例,培美曲塞500 mg／m2,静脉注射,顺铂75 mg／m2,第1天 ,21 d为1个周期。按WHO关于实体瘤治疗疗效评价标准和化疗毒性评价标准判断疗效和不良反应。结果　23例患者中近期有效7例（30.4 %）,中位生存期（OS）10.6个月,中位进展时间（TTP）为4.5个月。1 年总生存（OS）率为43.5 %（10／23）。主要不良反应为血液学毒性和消化道反应。Ⅲ～Ⅳ度中性粒细胞减少6例（26.1 %）,Ⅲ～Ⅳ度恶心、呕吐3例（13.0 %）。结论　培美曲塞联合顺铂方案对难治性转移性乳腺癌患者具有很好的疗效。     

吉西他滨为主的方案治疗经紫杉类和蒽环类治疗失败的转移性乳腺癌的疗效比较

目的 观察经紫杉类和蒽环类治疗失败的转移性乳腺癌患者分别采用吉西他滨联合卡培他滨或氟尿嘧啶（5-FU）、吉西他滨联合顺铂或卡铂和吉西他滨联合羟基喜树碱（HCPT）进行解救治疗的疗效与安全性,探讨转移性乳腺癌经紫杉类和蒽环类治疗进展后适合的化疗方案。方法 2006年12月至2012年12月间经紫杉类和蒽环类治疗后进展的65例转移性乳腺癌患者分为：GX方案组（n=34）：吉西他滨800～1000mg／m2,d1、d8;卡培他滨850～1000mg／m2 bid,d1～d14或5-FU 500mg／m2 d1～d5。GP方案组（n=21）：吉西他滨800～1000mg／m2,d1、d8;顺铂70mg／m2或卡铂AUC=4～6。GH方案组（n=10）：吉西他滨800～1000mg／m2,d1、d8;HCPT 6～8mg／d,持续用5～6天。21天为1周期,每两个周期评价疗效,获疾病控制的患者继续化疗至6个周期。结果 64例可评价疗效,65例可评价不良反应。GX方案组、GP方案组及GH方案组的有效率分别为36.4％、33.3％和30.0％,组间差异无统计学意义;中位无进展生存时间分别为8个月（1～22个月）、8个月（1～48个月）和6个月（2～12个月）,组间差异无统计学意义（P=0.415）;中位总生存时间分别为14.5个月（6～37个月）、14个月（4～48个月）和16个月（5～63个月）,组间差异无统计学意义（P=0.653）。3组的3～4级不良反应的发生率均较低。结论 以吉西他滨为主的方案对既往经紫杉类和蒽环类治疗后进展的转移性乳腺癌患者有一定疗效,不良反应可耐受,为有效的解救方案。     

晚期黑素瘤过继免疫治疗的Ⅱ期临床研究

目的：观察化疗联合细胞因子诱导的杀伤细胞（cytokine induced killer,CIK）治疗转移性恶性黑素瘤（metastatic melanoma,MM）的疗效及其安全性。方法：53例MM患者接受福莫司汀100mg/m2,第1～5天;氮烯咪胺400mg/d,第2～6天;CIK第7、14、和16天;每28d为1个周期的联合治疗,每2个周期评价疗效。结果：34例可评价患者中完全缓解（com-plete response,CR）1例（2.9%）,部分缓解（partial response,PR）7例（20.6%）,总有效率（overall response,ORR）为23.5%;疾病稳定（stable disease,SD）14例（44%）,临床获益率（clinical benefit rate,CBR）67.5%;中位无进展生存期（progressionfree survival,PFS）8个月;中位总生存期（overall survival,OS）11个月;乳酸脱氢酶（lactate dehydrogenase,LDH）正常者的OS长于升高者;有效或稳定患者的PFS和OS长于疾病进展（progression disease,PD）患者。不良反应中G3＋G4血小板减少41%,白细胞减少23.5%;发生2例超敏反应。无治疗相关死亡。结论：化疗联合CIK治疗MM患者耐受性尚好,有效率高于常规化疗,可延长LDH升高和疗效评价未PD患者的生存时间,但仍有待Ⅲ期临床研究进一步验证。     

依维莫司联合依西美坦治疗激素受体阳性、HER2阴性复发转移性乳腺癌的安全性及有效性分析

目的:观察依维莫司联合依西美坦治疗非甾体类芳香化酶抑制剂（NSAIs）耐药的激素受体阳性、HER2阴性绝经后晚期乳腺癌的安全性及疗效。方法:2014年8月10日至2016年9月20日收治的绝经后激素受体阳性、HER2阴性,NSAIs治疗后进展的晚期乳腺癌患者46例,随机进入研究组和对照组。研究组23例口服依维莫司10 mg/d及依西美坦2.5 mg/d;对照组23例口服依西美坦单药2.5 mg/d,分析两组患者的肿瘤控制率(DCR)、不良反应发生率、无进展生存期（PFS）。结果:中位随访时间9.5个月,研究组和对照组的DCR率分别为65.2%和34.8%,差异具有统计学意义（P=0.038）。研究组最常见的不良反应为口腔炎（65.2%）和乏力（47.8%）与对照组差异具有统计学意义（P＜0.05）。研究组和对照组的中位PFS分别为6.5个月(95%CI=4.8~8.2)和3.5个月(95%CI=2.7~4.3),差异有统计学意义（P=0.02）。结论:依维莫司联合依西美坦治疗绝经后NSAIs耐药的激素受体阳性、HER2阴性晚期乳腺癌的不良反应可控,可显著提高DCR率及PFS。     

多西他赛联合奈达铂治疗复发转移性鼻咽癌54例

 目的　评价多西他赛联合奈达铂治疗复发转移性鼻咽癌的近期疗效及患者不良反应。方法　54例复发转移性鼻咽癌患者接受多西他赛（75 mg／m2,第1天）和奈达铂（40 mg／m2,第1天至第3天）化疗,21 d为1个周期,2个周期后评价疗效及患者不良反应。结果　54例患者中有44例（81.5 %）获得缓解,其中完全缓解27例（50.0 %）,部分缓解17例（31.5 %）。不良反应主要为骨髓抑制。结论　多西他赛联合奈达铂治疗复发转移性鼻咽癌近期疗效较好。     

安罗替尼二线治疗38例铂类耐药晚期肺腺癌患者观察

  目的  分析安罗替尼二线治疗对铂类联合化疗耐药的晚期肺腺癌患者临床疗效及不良反应。  方法  回顾性分析2018年6月至2018年12月福建医科大学附属第二医院、中国人民解放军联勤保障部队第九〇〇医院收治的38例肺腺癌患者的临床资料,全部患者均行铂类联合化疗一线治疗后,疾病进展行安罗替尼靶向治疗。治疗方案为安罗替尼12 mg/d,服药2周停药1周,3周为1个周期,每2个周期后评价疗效。  结果  每例患者平均行6.3个周期安罗替尼治疗。38例患者无完全缓解（complete response,CR）,其中部分缓解（partial response,PR）为7例、疾病稳定（stable disease,SD）为21例、疾病进展（progression disease,PD）为10例。客观缓解率（objective response rate,ORR）为18.4%（7/38）,疾病控制率（disease control rate,DCR）为73.7%（28/38）。无进展生存期（progression-free survival,PFS）为5.5个月,中位生存期（median survival time,MST）为11.4个月。最常见不良反应为高血压、乏力、食欲减退、蛋白尿、手足皮肤反应,3/4级不良反应发生率为18.4%（7/38）;大部分患者能够耐受安罗替尼治疗。  结论  安罗替尼口服方便,且安罗替尼二线治疗对铂类联合化疗耐药的晚期肺腺癌患者具有较好的疗效和安全性。      

化疗联合内分泌治疗对标准治疗失败晚期转移性乳腺癌的探索性研究

目的 分析化疗与内分泌治疗联合应用于标准治疗失败的晚期转移性乳腺癌的临床价值.方法 30例标准治疗失败的晚期乳腺癌患者,应用依托泊苷[(VP16) 75 ～ 100 mg,每日1次,连续口服10d,21 d为1个周期]联合孕激素类药物(甲羟孕酮0.5 g,2次/d,或甲地孕酮160 mg,1次/d,连续口服21 d),评价疗效和生活质量.结果 30例患者该次治疗的中位治疗为6线(3～9线),总体临床获益率为16.7％(5/30),中位无进展生存4.0个月(1.0 ～ 13.0个月).结论 化疗(VP16)联合内分泌(孕激素类药物)治疗标准药物治疗失败的晚期乳腺癌患者是可选择的治疗手段.     

RECORD-2: phase II randomized study of everolimus and bevacizumab versus interferon α-2a and bevacizumab as first-line therapy in patients with metastatic renal cell carcinoma

BackgroundThe open-label, phase II RECORD-2 trial compared efficacy and safety of first-line everolimus plus bevacizumab (EVE/BEV) with interferon plus bevacizumab (IFN/BEV) in patients with metastatic renal cell carcinoma.Patients and methodsPreviously untreated patients were randomized 1:1 to bevacizumab 10 mg/kg every 2 weeks with either everolimus 10 mg/day (EVE/BEV) or interferon (9 MIU 3 times/week, if tolerated) (IFN/BEV). Tumor assessments occurred every 12 weeks. The primary objective was the assessment of treatment effect on progression-free survival (PFS), based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success).ResultsBaseline characteristics were balanced between the EVE/BEV (n = 182) and IFN/BEV (n = 183) arms. The median PFS was 9.3 and 10.0 months in the EVE/BEV and IFN/BEV arms, respectively (P = 0.485). The predicted probability of phase III success was 5.05% (hazard ratio = 0.91; 95% confidence interval 0.69–1.19). The median duration of exposure was 8.5 and 8.3 months for EVE/BEV and IFN/BEV, respectively. The percentage of patients discontinuing because of adverse events (AEs) was 23.4% for EVE/BEV and 26.9% for IFN/BEV. Common grade 3/4 AEs included proteinuria (24.4%), stomatitis (10.6%), and anemia (10.6%) for EVE/BEV and fatigue (17.1%), asthenia (14.4%), and proteinuria (10.5%) for IFN/BEV. The median overall survival was 27.1 months in both arms.ConclusionsThe efficacy of EVE/BEV and IFN/BEV appears similar. No new or unexpected safety findings were identified and, with the exception of proteinuria in about one-fourth of the population, EVE/BEV was generally well tolerated.Clinical trial registry and trial registration numberClinicalTrials.gov: NCT00719264.     

Everolimus Plus Letrozole for Treatment of Patients With HR+, HER2– Advanced Breast Cancer Progressing on Endocrine Therapy: An Open-label,Phase II Trial

Purpose

In the Breast cancer trials of OraL EveROlimus-2 (BOLERO-2) trial, everolimus plus exemestane improved progression-free survival (PFS) in patients with hormone receptor-positive (HR⁺), human epidermal growth factor receptor 2-negative (HER2^?) advanced breast cancer (ABC) recurring or progressing on/after prior endocrine therapy (ET), suggesting that dual blockade using targeted therapy and ET was an effective treatment option. Here, we investigated the clinical benefit of combining everolimus with different endocrine partner, letrozole, in a similar patient population.

Safety and Efficacy of Everolimus With Exemestane vs. Exemestane Alone in Elderly Patients With HER2-Negative,Hormone Receptor–Positive Breast Cancer in BOLERO-2

BackgroundPostmenopausal women with hormone receptor–positive (HR⁺) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR⁺ advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest.Patients and MethodsBOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR⁺ advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up.ResultsBaseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths.ConclusionAdding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR⁺ advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population.     

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR⁺) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655.     

Safety and efficacy of everolimus (EVE) plus exemestane (EXE) in postmenopausal women with locally advanced or metastatic breast cancer: final results from EVEREXES

Background

This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC).

Methods

The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE?+?EXE in patients with HR+, HER2???ABC in Asia and other emerging growth countries. Postmenopausal women with HR+, HER2???ABC who had documented recurrence or progression, following a nonsteroidal aromatase inhibitor therapy, were treated with EVE (10 mg/day)?+?EXE (25 mg/day) orally.

Results

A total of 235 patients received?≥?1 dose of study medication. At the end of the study, all patients ceased the treatment. Disease progression (66.0%) was the primary reason of discontinuation. The most common AEs (≥?20%) were stomatitis, decreased appetite, hyperglycemia, rash, aspartate aminotransferase increased, anemia, alanine aminotransferase increased, cough, and fatigue. No new safety concerns were identified in the current study. Median progression-free survival (PFS) in the Asian subset was similar to that of the overall population (9.3 months in both groups). Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE?+?EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained.

Conclusion

The safety and efficacy results from EVEREXES trial are consistent to data previously reported in BOLERO-2. These results support that EVE?+?EXE could be a viable treatment option for the postmenopausal women with HR+, HER2???ABC in Asian region.

     

Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer

To determine the feasible dose and schedule for everolimus, an oral mTOR inhibitor, combined with vinorelbine and trastuzumab for patients with HER2-overexpressing metastatic breast cancer pretreated with trastuzumab. In this phase Ib multicenter, Bayesian dose-escalation study, 50 patients received everolimus 5 mg/day, 20 mg/week, or 30 mg/week plus vinorelbine (25 mg/m² on day 1 and 8 every 3 weeks) and trastuzumab (2 mg/kg weekly). Endpoints included end-of-cycle-1 dose-limiting toxicity (DLT) rate (primary endpoint), safety, relative dose intensity, overall response rate (ORR), and pharmacokinetics. Grade 3/4 neutropenia was the most common end-of-cycle-1 DLT and occurred in 10 of 30 and 4 of 14 patients in the 5 mg/day and 30 mg/week cohorts, respectively. Other end-of-cycle-1 DLTs included single cases of febrile neutropenia, grade 3 stomatitis with concomitant fatigue, grade 2 stomatitis, grade 3 anorexia, and grade 2 acneiform dermatitis, all in the 5-mg/day cohort. Based on the recorded DLTs and global safety, everolimus 5 mg/day and 30 mg/week were chosen as the optimal dose levels for the daily and weekly arms. Forty-seven patients were evaluable for efficacy. ORR was 19.1%, with a disease control rate of 83.0% and median progression-free survival of 30.7 weeks. No drug interaction was observed between everolimus and vinorelbine. Everolimus combined with weekly vinorelbine and trastuzumab generally was well tolerated and had encouraging antitumor activity in heavily pretreated patients with HER2-overexpressing metastatic breast cancer that progressed on trastuzumab (NCT00426530).     

Everolimus in advanced,progressive, well‐differentiated,non‐functional neuroendocrine tumors: RADIANT‐4 lung subgroup analysis

In the phase III RADIANT‐4 study, everolimus improved median progression‐free survival (PFS) by 7.1 months in patients with advanced, progressive, well‐differentiated (grade 1 or grade 2), non‐functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35‐0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT‐4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8‐10.9) months in the everolimus arm vs 3.6 (1.9‐5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28‐0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3‐4 drug‐related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well‐differentiated, non‐functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT‐4 cohort. These results support the use of everolimus in patients with advanced, non‐functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783).     

Clinical effect of idarubicin on malignant lymphoma]

The anti-tumor efficacy and safety of idarubicin (IDR) were investigated among patients in whom the standard therapy for malignant lymphoma had failed or who had suffered a recurrence. IDR was administered at a dose of 12 mg/m2 or 15 mg/m2 by a single i.v. bolus, and this dosage regimen was repeated every 3 weeks. Among total of 21 evaluable patients, there were 3 CRs and 1 PR, for an overall response rate of 19.0% (4/21). All patients who attained CR were cases which had recurred after receiving combination chemotherapy including doxorubicin. Adverse reactions were bone marrow suppression, including leucopenia (90.5%), neutropenia (95.2%), and thrombocytopenia (47.6%); gastrointestinal symptoms such as nausea/vomiting (42.9%) and stomatitis (9.5%); alopecia (23.8%) and fever (19.0%). These results indicate that IDR is effective against refractory malignant lymphoma.     

Phase 2 study of everolimus monotherapy in patients with nonfunctioning neuroendocrine tumors or pheochromocytomas/paragangliomas

BACKGROUND:

The current study was conducted to evaluate the efficacy and safety of everolimus in the treatment of patients with nonfunctioning neuroendocrine tumors (NETs) or pheochromocytomas/paragangliomas.

METHODS:

Patients with histologically confirmed nonfunctioning NETs or pheochromocytomas/paragangliomas and with documented disease progression before study enrollment were eligible for the current study. Everolimus was administered daily at a dose of 10 mg for 4 weeks. Response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST; version 1.0) every 8 weeks. The primary endpoint was the 4‐month progression‐free survival rate (PFSR). The hypothesis of the current study was that the 4‐month PFSR would increase from 50% to 65%. Safety was evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0).

RESULTS:

A total of 34 patients were enrolled. Of these, 27 patients had nonfunctioning NETs, 5 had pheochromocytomas, and 2 had paragangliomas. The 4‐month PFSR was 78%. Partial response (PR) was observed in 3 patients. Twenty‐eight patients had stable disease (SD) and 2 patients developed progressive disease (PD). The response rate (RR) and overall disease control rate (DCR) were 9.0% (95% confidence interval [95% CI], 0%‐18.6%) and 93.9% (95% CI, 85.8%‐100%), respectively. The PFS was 15.3 months (95% CI, 4.6 months‐26.0 months). Of the patients with nonfunctioning NETs, 3 achieved a PR and 23 had SD (RR, 11.1%; DCR, 100%); the PFS was 17.1 months (95% CI, 11.1 months‐23.0 months) and the 4‐month PFSR was 90.0%. Twenty‐one patients (80.8%) demonstrated tumor shrinkage. In 7 patients with pheochromocytomas/paragangliomas, 5 achieved SD, and 2 developed PD. The PFS was 3.8 months (95% CI, 0.5 months‐7.0 months) and the 4‐month PFSR was 42.9%. Four patients demonstrated tumor shrinkage. The major grade 3/4 adverse events were thrombocytopenia (14.7%), hyperglycemia (5.9%), stomatitis (5.9%), and anemia (5.9%).

CONCLUSIONS:

Everolimus was associated with high therapeutic efficacy and tolerability in patients with nonfunctioning NETs, and demonstrated modest efficacy in patients with pheochromocytomas/paragangliomas. Cancer 2012. © 2012 American Cancer Society.