front-line treatment

  • 文章类型: Case Reports
    一半的非小细胞肺癌(NSCLC)患者年龄超过70岁,由于耐受性差,治疗选择有限,在大多数临床试验中被排除在外。盐酸安洛替尼,一种新型口服多靶点酪氨酸激酶抑制剂,在中国已被批准用于非小细胞肺癌的标准三线治疗。在此,我们报告了一位没有任何驱动基因突变的老年NSCLC患者,他正在接受安洛替尼作为一线治疗,并获得了长期生存。
    这名77岁的男性患者在进行了一周的体力活动后,因胸闷入院。该患者已被诊断为IIIB期驱动基因阴性鳞状细胞肺癌。之后,从首次诊断到最后的疾病进展,患者接受安洛替尼治疗2年零10个月。简而言之,安洛替尼联合铂类化疗作为一线治疗方案,共进行了6个周期.经过6个周期的安洛替尼单一治疗维持,疾病进展发生。然后,安洛替尼联合替加氟作为抢救治疗,疾病再次得到控制。经过29个周期的安洛替尼联合替加氟方案,疾病终于进展了。在使用安洛替尼作为一线治疗后,患者实现了总共34个月的无进展生存期。他现在仍然保持着良好的表现状态(表现状态得分:1)。
    该患者使用安洛替尼作为一线方案联合化疗实现了长期生存。
    UNASSIGNED: Half of the population of non-small cell lung cancer (NSCLC) patients are older than 70 years and have limited therapeutic options due to poor tolerance and being excluded in most clinical trials. Anlotinib hydrochloride, a novel oral multi-target tyrosine kinase inhibitor, has been approved for the standard third-line treatment for NSCLC in China. Herein we report an elderly NSCLC patient without any driver gene mutations who was undergoing anlotinib as a front-line treatment and who achieved long-term survival.
    UNASSIGNED: The 77-year-old male patient was admitted to the hospital for chest tightness after engaging in physical activity for a week. The patient has been diagnosed with stage IIIB driver gene-negative squamous cell lung carcinoma. After that, he was treated with anlotinib for 2 years and 10 months from the first diagnosis until the last disease progression. Briefly, anlotinib combined with platinum-based chemotherapy was performed as the first-line therapy over six cycles. After 6 more cycles of anlotinib monotherapy maintenance, disease progression occurred. Then, anlotinib combined with tegafur was administered as a salvage treatment, and the disease was controlled again. After 29 cycles of anlotinib combined with tegafur regimens, the disease progressed finally. The patient achieved a total of 34 months of progression-free survival after anlotinib was used as the front-line treatment. He is still alive with a good performance status now (performance status score: 1).
    UNASSIGNED: This patient achieved long-term survival using anlotinib as a front-line regimen combined with chemotherapy.
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  • 文章类型: Multicenter Study
    蛋白酶体抑制剂(PIs)的使用,新的免疫调节剂(IMiDs),和其他新药,大剂量化疗联合自体干细胞移植显著提高了年轻多发性骨髓瘤(MM)患者的生存率.然而,老年患者的生存率改善仍然不足.尚未开发出针对老年MM患者的最佳治疗推荐模型,尤其是在现实世界中的研究很少。
    我们回顾性分析了328例(≥65岁)MM患者在真实世界中的治疗模式和结果。根据诱导方案将患者分为三组。
    该队列的中位年龄为70(65-86)岁。将患者分为第1组(基于PI的方案,n=218),第2组(基于IMID的方案,n=48)和第3组(PI+IMiD,n=62)。第3组的诱导方案产生的总反应率高于第1组和第2组(85.42%vs.71.08%与66.67%,p=0.016)。该队列的中位随访时间为30个月(四分位距[IQR]18-36)。对于整个队列,中位无进展生存期(PFS)为26(IQR12.00-42.89)个月,总生存期(OS)为60(IQR40.00-67.20)个月。三组的PFS无显著差异(28个月vs.18个月vs.26个月,p=0.182)。操作系统也是如此(60个月vs.59个月vs.没有到达,p=0.067)。多变量分析表明,年龄>70岁,虚弱状态(老年脆弱性评分),诱导功效<部分缓解,无维持治疗是OS预后不良的独立因素。
    组合PI和IMiD的一线诱导方案比基于单一PI或IMiD的方案产生了更深的反应。维持治疗可以进一步改善真实世界中老年MM患者的临床结果。
    The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high-dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world.
    We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real-world setting. Patients were divided into three groups according to induction regimens.
    The median age of the cohort was 70 (65-86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow-up of the cohort was 30 (interquartile range [IQR] 18-36) months. For the entire cohort median progression-free survival (PFS) was 26 (IQR 12.00-42.89) months and overall survival (OS) was 60 (IQR 40.00-67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy < partial remission, and no maintenance treatment were independent poor prognostic factors for OS.
    Front-line induction regimens combining PIs and IMiDs developed more deep response than single PI or IMiD based regimens. Maintenance treatment can further improve the clinical outcome in elderly MM patients in real-world setting.
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  • 文章类型: Journal Article
    OBJECTIVE: The main objective was to evaluate the activity and tolerability of TEMIRI as a front-line treatment in primary disseminated Ewing sarcoma (PDMES) using the RECIST 1.1 criteria. The secondary objectives included the assessment of toxicity and the performance status/symptom changes.
    METHODS: Between 2012 and 2018, patients with PDMES received two courses of temozolomide 100 mg/sqm/day + irinotecan 50 mg/sqm/day for 5 days every 3 weeks as an amendment to the Italian Sarcoma Group/Associazione Italiana EmatoIogia ed Oncologia Pediatrica (ISG/AIEOP) EW-2 protocol (EUDRACT#2009-012353-37, Vers. 1.02).
    RESULTS: Thirty-four patients were enrolled. The median age at diagnosis was 19 years (range 3-55). After TEMIRI, the RECIST response was as follows: a partial response in 20 (59%) patients, stable disease in 11 (32%), and disease progression in 3 (9%). The ECOG/Lansky score was improved in 25/34 (73.5%) cases, and a reduction or disappearance of pain was observed in 31/34 patients (91%). The incidence of grade 3-4 toxicity was 3%. The 3-year event-free survival (EFS) and overall survival (OS) were 21% (95% CI 6-35%) and 36% (95% CI: 18-54%), respectively.
    CONCLUSIONS: the smooth handling and encouraging activity demonstrated by up-front TEMIRI did not change the EFS in PDMES, so this result suggests the need for the further evaluation of the efficacy of TEMIRI in combination with conventional treatments in non-metastatic patients.
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  • 文章类型: Journal Article
    BACKGROUND: Bortezomib-related peripheral neuropathy (PN) affects a relevant proportion of multiple myeloma (MM) patients treated with melphalan, prednisone, and bortezomib (VMP). Empirical dose modifications have attempted to reduce toxicity without compromising efficacy.
    METHODS: We retrospectively evaluated the dose-response and dose-toxicity relationships in 114 unselected untreated MM patients intended for treatment with VMP with subcutaneous bortezomib.
    RESULTS: Sixty-two patients (54%) completed the 9 scheduled cycles. Median treatment duration was 48 weeks (range 1-57), cumulative bortezomib dose was 41.8 mg/m2 (2.6-67.6) and median dose intensity was 1.0 mg/m2 /wk (0.2-2.6). Median progression-free survival (PFS) and overall survival (OS) for the full cohort were 86 weeks (95%CI 77-104) and 209 weeks (95% CI 157-259) respectively. Patients who progressed <60 days after discontinuing bortezomib had received a significantly inferior mean cumulative dose, 34.6 mg/m2 than the remaining individuals, 45.5 (P = .023). PFS was significantly improved for patients achieving a very good partial response (VGPR) or better (P = .00007). Additional variables with a prognostic impact on PFS on univariate analysis included completion of the 9 scheduled cycles (P = .00002), patients with at least 50 weeks of treatment (P = .02) and patients receiving a cumulative dose of at least 49 mg/m2 (P = .05). Achievement of a VGPR (HR 0.23; 95%CI 0.12-0.46; P = .00002) and a cumulative dose of 49 mg/m2 (HR 0.46, 95%CI 0.27-0.78; P = .003) were statistically independent prognostic factors for PFS. Toxicity-related treatment dose reductions occurred in 75 individuals (66%). PN was observed in 50 individuals (44.6%), grade 3 in 9 (8%). The only prognostic factor for emergence of PN in multivariate analysis was the presence of baseline PN.
    CONCLUSIONS: Biweekly full-dose treatment in the first cycles has a major impact in depth of response. Depth of response, cumulative bortezomib dose, and treatment duration had an impact in prolongation of PFS.
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  • 文章类型: Case Reports
    UNASSIGNED: Ribociclib is an orally bioavailable cyclin-dependent kinase 4/6 inhibitor. In combination with aromatase inhibitor letrozole, it has approval for treatment of hormone receptor positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. First-line therapy with ribociclib + letrozole significantly improves progression-free survival compared to placebo + letrozole in patients with HR+/HER2- advanced breast cancer. In patients with de novo advanced or metastatic breast cancer, ribociclib was able to provide substantial clinical benefit according to data from the MONALEESA-2 study.
    UNASSIGNED: Here, we report the complete clinical response in a postmenopausal patient with de novo, locally advanced, pulmonary metastatic breast cancer treated with ribociclib + letrozole. Our patient presented an ulcerated breast-consuming tumor with multiple pulmonary metastases. HR+/HER2- breast cancer was confirmed by tumor biopsy. Ki67 expression was 90%. After three months of initial treatment, the tumor-associated ulcerations disappeared, and no measurable pulmonary disease was detectable on CT scan. Treatment was well tolerated, and after dosage reduction due to neutropenia, no further side effects have been documented. At present, complete clinical response remains after 15 months of ongoing treatment.
    UNASSIGNED: This case report documents an exceptional tumor response of a fast growing, locally advanced, pulmonary metastatic HR+/HER2- de novo breast cancer treated by ribociclib/letrozole combination therapy. Treatment success was long lasting with few side effects. The patient was very satisfied with the treatment and had no specific restrictions in her daily life.
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  • 文章类型: Clinical Trial, Phase II
    This Phase II trial evaluated the efficacy of bendamustine, bortezomib and rituximab in patients with previously untreated low-grade lymphoma. Eligible patients had low grade lymphoma with no previous systemic disease treatment. Treatment for all patients was given in 28-day cycles for a maximum of 6 cycles. Patients received rituximab 375 mg/m2 intravenously (IV) on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6; bendamustine 90 mg/m2 IV on days 1 and 2; and bortezomib 1·6 mg/m2 IV on days 1, 8 and 15. Patients were permitted to begin maintenance treatment with rituximab 6 months after completion of study treatment and after 6-month follow-up assessments had been conducted. Fifty-four eligible patients were enrolled. The most common grade 3/4 toxicities were leucopenia (28%), neutropenia (30%) and lymphopenia (17%). There were no treatment-related deaths and 1 unrelated death on study (embolic stroke). The overall response rate was 94% for all patients. The median follow-up was 54 months. Kaplan-Meier estimates of progression-free survival and overall survival at 36 months were 75% and 88%, respectively. The treatment regimen was well tolerated and produced high response rates. Further study of this regimen in patients with previously untreated lymphoma is warranted.
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  • 文章类型: Journal Article
    BACKGROUND: About 75% of patients with chronic lymphocytic leukemia (CLL) are more than 65 years at the time of diagnosis. Treatment of the elderly remains complicated due to multiple factors, such as comorbidities, decline in functional reserve and fitness. Since chronological age by itself cannot properly predict life expectancy and treatment tolerance, an accurate assessment of the fitness status is of crucial importance for an optimal treatment choice. Areas covered: This review will discuss the most relevant aspects concerning the issues experienced in the management of elderly/unfit patients with CLL. The most frequently observed age-related toxicities, fitness assessments, supportive care measures and treatment options for elderly patients and for patients who are deemed unfit will be discussed. Literature search methodology included examination of PubMed index. Expert commentary: During the last decade, different trials focusing on elderly/unfit patients have investigated more tolerable chemoimmunotherapy schedules and, more recently, the activity and safety of chemo-free regimens. Chlorambucil combined with an anti-CD20 monoclonal antibody has shown clinical activity with a relatively good profile of toxicity. The recent introduction of the B-cell receptor antagonists, ibrutinib and idelalisib, and other targeted drugs in development (e.g. venetoclax), is broadening the therapeutic armamentarium of elderly CLL patients.
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