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The OS benefit observed with nivolumab compared with investigator’s choice of single-agent chemotherapy for patients with recurrent or metastatic head and neck squamous cell carcinoma who previously received platinum therapy occurred regardless of patient age, according to a post hoc analysis of the CheckMate 141 trial presented at Chemotherapy Foundation Symposium. In addition, objective response rates were higher with nivolumab (Opdivo, Bristol-Myers Squibb) among patients aged younger than 65 years, as well as those aged 65 years or older. Results of the phase 3 CheckMate 141 trial showed nivolumab, an anti-PD-1 antibody, significantly prolonged OS compared with investigator’s choice of single-agent chemotherapy among patients with recurrent or metastatic squamous cell carcinoma who underwent prior platinum therapy (median, 7.5 months vs. 5.1 months; HR = 0.7; 97.73% Ci, 0.51-0.96). Researchers observed the benefit at 1-year and 2-year follow-up, regardless of tumor PD-L1 expression or HPV status. In addition, after minimum follow-up of 24.2 months, incidence of grade 3 or grade 4 treatment-related adverse events was lower in the nivolumab group (15.3% vs. 36.9%). A considerable percentage of patients with HNSCC are aged 65 years or older, and they often have comorbidities that may limit their ability to tolerate chemotherapy. However, data on use of immune checkpoint inhibitors among elderly patients with HNSCC are lacking, according to study background. Nabil F. Saba, MD, FACP, professor in the department of hematology and medical oncology at Winship Cancer Institute at Emory University, and colleagues presented results of a post-hoc analysis of CheckMate 141 that explored outcomes based on patient age. The randomized, phase 3 trial included 361 patients with recurrent or metastatic HNSCC of the oral cavity, pharynx or larynx who experienced progression at least 6 months after platinum therapy in the adjuvant, primary, recurrent or metastatic setting. Researchers assigned 240 patients to nivolumab 3 mg/kg every 2 weeks. The other 121 patients received investigator’s choice of chemotherapy, which included methotrexate, docetaxel or cetuximab (Erbitux, Eli Lilly). OS served as the primary endpoint. Secondary endpoints included PFS, ORR, duration of response, safety, biomarkers and patient-reported quality of life. The post-hoc analysis included 113 patients aged 65 years or older (nivolumab, n = 68; chemotherapy, n = 45). Data cutoff was September 2017, and minimum follow-up was 24.2 months. Median duration of therapy did not differ significantly between patients aged younger than 65 years or 65 years and older in either treatment group. Article Source: https://www.healio.com/hematology-oncology/head-neck-cancer/news/online/34a8fb6b-c4d2-4ce9-bf06-4d0fb4c7df23/nivolumab-benefit-in-advanced-head-and-neck-cancer-maintained-regardless-of-age

根据发表于Journal of Clinical Oncology的 2期研究结果，泊马度胺加低剂量地塞米松改善了复发/难治性多发性骨髓瘤和中度至重度肾功能损害患者的反应。 该组合也表现出良好的耐受性。 “肾功能损害是多发性骨髓瘤的常见合并症。大约20％至30％的多发性骨髓瘤患者在诊断时出现肾功能损害，约10％需要透析，“ 雅典大学医学院临床治疗学教授兼主席Meletios Dimopoulos及其同事中写道。“随着时间的推移，患有多发性骨髓瘤的患者可能会出现肾功能损害，这与预后不良和生存期短有关。” 这些患者的中位OS为2年。 Dimopoulos及其同事在非比较性MM-013试验中招募了81名患有复发/难治性多发性骨髓瘤的患者（中位年龄72岁）。 研究人员将患者分为三组：中度肾功能损害（估计肾小球滤过率，30 mL / min / 1.73 m 2至45 mL / min / 1.73 m 2），严重肾功能损害（估计肾小球滤过率，小于30 mL / min） /1.73 m 2）或需要血液透析的严重肾功能损害。 患者经历了四次中位抗凝血症方案的中位数。 患者在第1天至第21天每天接受4mg 泊马度胺（Pomalyst，Celgene），并且在28天周期中每周一次接受20mg或40mg地塞米松。 总体响应率作为主要终点。中位随访时间为8.6个月。 中度肾功能不全患者的ORR为39.4％，严重损害患者为32.4％，需要血液透析的患者为ORR的14.3％。 中度肾功能不全患者的中位反应持续时间为14.7个月，严重肾功能不全患者为4.6个月。尚未达到需要血液透析的患者的中位反应时间。 所有中度肾功能不全患者均表现出疾病控制，而79.4％的严重肾功能不全患者和78.6％需要血液透析的严重肾功能不全患者表现出疾病控制。 中位操作系统是： 中度肾功能不全患者16.4个月; 严重肾功能不全患者11.8个月; 和 需要血液透析的严重肾功能不全患者需5.2个月。 研究人员观察到18.2％的中度损伤患者完全肾脏反应。 没有在基线需要血液透析的患者变得不依赖于透析。 数据截止时仍有13名患者继续接受治疗。 16％的患者出现需要减少剂量的不良事件。 最常见的3级或4级治疗相关不良事件包括中性粒细胞减少症（53.1％），贫血症（35.8％），感染（32.1％），血小板减少症（27.2％），疲劳（6.2％），高钾血症（6.2％），肾功能衰竭（6.2％），低钙血症（4.9％），发热（2.5％）和外周水肿（1.2％）。 “MM-013试验是第一项提供证据证明这些患者可以从泊马度胺加低剂量地塞米松治疗中获益的证据，并支持使用这种治疗复发/难治性多发性骨髓瘤和严重肾功能不全的患者，包括那些接受血液透析的人，“研究人员写道。“实现疾病控制和稳定具有重要的临床益处，特别是对于需要血液透析的患者。 “这里提供的结果增加了多发性骨髓瘤和肾功能不全晚期患者治疗选择的有限证据，并将帮助医疗保健提供者为这一患者群体做出适当的治疗选择，”他们补充说。 文章来源： https://www.healio.com/hematology-oncology/myeloma/news/in-the-journals/%7Bf2a2a191-ed73-4699-ac70-213db5008645%7D/pomalidomide-low-dose-dexamethasone-active-in-multiple-myeloma-with-renal-impairment

Imatinib Determined the Most Cost-Effective Frontline TKI for Chronic Myeloid Leukemia The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) to the treatment of chronic myeloid leukemia (CML) dramatically changed long-term outcomes.1 Now, there are several TKI options, and optimal treatment selection can be challenging given differences in patient characteristics and cost of therapy. “While successful therapeutic outcomes and long-term survival are clearly the main goal of TKI treatment, patients are also faced with lifelong management of the financial aspects of being diagnosed with CML and affording treatment,” Giuseppe Saglio, MD, of the San Luigi Hospital in Turin, Italy, and Elias Jabbour, MD, of The University of Texas MD Anderson Cancer Center, Houston, wrote.1 Imatinib, a first-generation TKI that was approved by the US Food and Drug Administration (FDA) in 2002, dramatically improved survival compared with the previous standard of care, which was the combination of interferon-α and cytarabine. The 10-year overall survival (OS) with imatinib is estimated at 83% compared with a 5-year OS of 68% with interferon-α plus cytarabine.1 Since then, the second-generation TKIs have emerged — dasatinib was first approved by the FDA in 2006 and nilotinib in 2007. Both agents can induce faster and deeper treatment responses compared with imatinib, but the safety profiles differ, so must also be considered, particularly when selecting first-line therapy.2 Cost-effectiveness should also be measured, as expenses increase for both the patient and the payer as CML becomes a chronic disease. Cost-effectiveness analyses have been conducted that compare the TKIs to each other, but these results will change as generic formulations become available. In 2016, Gleevec (imatinib) lost its exclusivity, resulting in the introduction of the generic formulation of imatinib.1Dasatinib and nilotinib will lose their exclusivity in the coming years, which will further change the cost-effectiveness of these agents. Cost-effectiveness of TKIs for CML treatment is, therefore, a complex topic that requires consideration of multiple factors — not just apparent costs to payers. Article Source: 文章来源： https://www.cancertherapyadvisor.com/chronic-myeloid-leukemia/imatinib-determined-most-cost-effective-frontline-tki-chronic-myeloid-leukemia/article/812167/

Dose escalation may combat worsening anemia during early ruxolitinib therapy in patients with myelofibrosis, according to a recent study published in the Journal of Hematology and Oncology. Ruxolitinib improves splenomegaly and alleviates the symptoms of intermediate-2 or high-risk myelofibrosis. However, its use is associated with an increased risk of developing grade 3/4 anemia and/or thrombocytopenia, requiring additional dose reductions or transfusions. The authors of the study aimed to preserve clinical benefit, but reduce hematologic risk early during treatment using dose escalation. The study was an open-label phase 2 study of 45 patients with myelofibrosis, 68.9% of whom had a Dynamic International Prognostic Scoring System score of 1 to 2, indicating intermediate disease risk. Patients received ruxolitinib 10 mg twice daily with increases in increments of 5 mg at 12 weeks and 18 weeks for a maximum dose of 20 mg. Symptom severity was assessed using the Myelofibrosis Symptom Assessment Form Total Symptom Score. The median percentage change in spleen volume at 24 weeks from baseline was 17.3% with a clear dose response. Similarly, the median Myelofibrosis Symptom Assessment Form Total Symptom Score also showed a clear dose response and had a median percentage change of 45.6%. Incidence of grade 3/4 anemia (20%), dose decreases due to anemia (11.1%), or thrombocytopenia (6.7%) were uncommon. Other observed adverse effects were anemia (26.7%), fatigue (22.2%), and arthralgias (20%). According to the authors, “dose-escalation approach may mitigate worsening anemia during early ruxolitinib therapy in some patients with myelofibrosis.” Article Source: https://www.oncologynurseadvisor.com/myeloproliferative-neoplasms/dose-escalation-mitigates-adverse-events-with-ruxolitinib-for-mf/article/814455/

Following a diagnosis of adrenal cancer, there are several treatment options that may be used. Each of these techniques has unique advantages and disadvantages that will make it preferable for some cases and not others. As adrenal cancer is relatively rare, it can be worthwhile to collaborate with other endocrine specialists to discuss the best treatment options for the particular case. The treatment of adrenal cancer typically involves a multidisciplinary team a may include surgeons, endocrinologists, radiation oncologists, medical oncologists, nurses, psychologists, social workers, and other health professionals. Surgery The most common treatment for adrenal cancer is adrenalectomy or surgical removal of the adrenal gland. In this procedure, the cancer is removed as much as possible, including areas where the cancer has spread to such as nearby lymph nodes. The procedure can be performed in two main ways: through an incision in the back below the ribs or an incision in the front of the abdomen. The incision in the back is useful to remove small tumors but can be difficult for larger tumors. As such, the incision in the front of the abdomen is the most common method used in practice. If the cancer has metastasized to other areas of the body, such as the liver, surgical removal of these secondary tumors may also be needed. For small adrenal tumors, a laparoscope can also be inserted into the adrenal gland to view the tumor and remove it. This is most commonly used for smaller tumors and helps to reduce recovery time. However, it cannot be used for larger tumors as the whole tumor should be removed in one piece to reduce the risk of recurrence. Radiation therapy Radiotherapy, which involves a focused beam of high-energy radiation, can be used to target the region of the cancerous cells in the adrenal gland. This is usually used as adjuvant therapy, in addition to other techniques such as surgery. There are two main types of radiation therapy that may be used: external beam radiation therapy and internal radiation therapy (brachytherapy). External beam radiation therapy uses a machine outside of the body to direct the radiation towards the adrenal gland. The radiation is usually administered once or twice a day, five days a week for a treatment period of approximately 6 weeks. In this type of radiation therapy, the surrounding tissue that the radiation passes through before it reaches the tumor is also affected. Treatment times are kept short to minimize this, but some adverse effects may be experienced. Internal radiation therapy, also known as brachytherapy, uses small pellets of radioactive material, which are placed inside the body next to or inside the tumor. This is usually left inside the body for a few days then removed. The localization of the radiation helps to reduce exposure to the surrounding tissues. Chemotherapy Chemotherapy for patients with adrenal cancer may be administered via intravenous injection or oral medications. This technique is usually reserved for patients with stage 4 adrenal cancers because it can help to destroy cancer cells in several parts of the body simultaneously. For cancer contained in the adrenal gland, surgical removal is usually preferred. Mitotane is a common chemotherapeutic agent used for adrenal gland because it can block adrenal gland hormone production and destroys cancers cells. It is particularly useful for cancers caused by excessive hormone production. Like other chemotherapeutic agents, it also destroys some healthy cells in this process. Other chemotherapeutic agents, which are often used in combination with mitotane, may include: Cisplatin Doxorubicin Etoposide Streptozocin Paclitaxel 5-fluorouracil Vincristine Other medications There are several other medications that may be used in the treatment of adrenal cancer, primarily to reduce the production of hormones related to the tumor. These may include: Ketoconazole and Metyrapone to reduce the production of adrenal steroid hormones Spironolactone to decrease the effects of aldosterone Mifepristone to decrease the effects of cortisol Tamoxifen, Toremifene, and Fulvestrant to block the effects of estrogen Article Source: https://www.news-medical.net/health/Adrenal-Cancer-Treatment.aspx

SAN ANTONIO — Riociguat is associated with improvements in right ventricular (RV) function in patients with pulmonary arterial hypertension(PAH) compared with placebo, according to a study presented at the CHEST Annual Meeting, held October 6-10, 2018, in San Antonio, Texas. Riociguat improved functional measures such as the 6-minute walk distance (6MWD), World Health Organization functional class, and N-terminal pro-brain natriuretic peptide in the PATENT-1 study (ClinicalTrials.gov Identifier: NCT00810693). The agent also demonstrated improvements in hemodynamic parameters, including pulmonary vascular resistance (PVR) and cardiac index (CI). “However, mortality in PAH is usually related to RV failure and so we performed a post hoc analysis to determine if riociguat improved hemodynamic parameters of RV function in PATENT-1,” researchers noted. Patients with PAH and a 6MWD between 150 and 450 m, PVR of >300 dyn⋅s⋅cm−5, and mean pulmonary arterial pressure (mPAP) of ≥25 mm Hg at baseline were enrolled. The investigators randomly assigned patients to either riociguat at up to 2.5 mg 3 times daily (n=254) or placebo (n=126) for a 12-week treatment period. At 12-week follow-up, the researchers performed right heart catheterization, and stroke volume (SV, mL), stroke volume index (SVI, mL/m2), RV work (cardiac output × mPAP × 0.0144), RV work index (CI × mPAP × 0.0144), RV power (mPAP × CI), cardiac efficiency (SV/mPAP), and pulmonary artery (PA) elastance (systolic pulmonary artery pressure/SV) were assessed. At 12-week follow-up, riociguat was associated with increases in RV work (+0.30 ±0.78), RV work index (+0.17 ±0.46), RV power (+0.05 ±0.12), SV (+10.63 ±13.68), SVI (+6.16 ±7.87), and cardiac efficiency (+0.44 ±0.60) from baseline. Additionally, treatment with riociguat demonstrated a decrease in PA elastance (–0.34 ±0.53). Patients who received placebo had decreases in RV work (–0.10 ±0.94), RV work index (–0.07±0.57), RV power (–0.02±0.15), and SVI (–0.04±9.52) at 12 weeks compared with baseline. Placebo was also associated with increases in PA elastance (+0.02±0.65), SV (+0.33±16.30), and cardiac efficiency (+0.09±0.57). Article Source: https://www.pulmonologyadvisor.com/chest-2018/pulmonary-arterial-hypertension-riociguat-right-ventricular-hemodynamics/article/805972/

2018年7月19日 代表的的EBMT的急性白血病工作组（ALWP），托马斯·海尼克从奥托-冯-格里克大学，马格德堡，德国，和他的同事回顾性分析（AML）患者在第一或第二完全缓解CR1急性髓性白血病的结果（或CR2）在白消安/氟达拉滨（BuFlu）后进行异基因造血干细胞移植（allo-HSCT），顺序FLAMSA（氟达拉滨+ Ara-C + amsacrine化疗），然后是环磷酰胺加全身照射（FLAMSA-TBI）或环磷酰胺加白消安（FLAMSA-Bu）调理。该研究发表在“骨与骨髓移植生物学”的印刷版之前。 数据来自EBMT登记处的ALWP。在2005年1月至2016年6月期间，在CR1或CR2中接受allo-HSCT的AML患者被纳入分析。患者接受BuFlu（n = 1,197;中位年龄= 58.8岁[范围，20.1-76]）或FLAMSA-TBI（n = 258;中位年龄= 47岁[范围，18.1-66.8]）或FLAMSA-Bu（n = 141;中位年龄= 59.6岁[范围，19.6-74.4]）。 该研究的主要终点是无白血病生存（LFS）。次要终点包括总生存期（OS），精确移植物抗宿主病无生存期，无复发生存期（GRFS），中性粒细胞植入，急性和慢性移植物抗宿主病（GvHD），复发率（RI）和非复发死亡率（NRM）。 主要发现： 中位随访：24.72个月 BuFlu vs FLAMSA-TBI vs FLAMSA-Bu组： 2年LFS：53.6％vs 61.6％vs 50.1％，P = 0.03 2年OS：60％vs 68.3％vs 56.4％NS GRFS：40.2％vs 46.9％vs 38.1％，NS 中性粒细胞移植：99.75％对 97.7％对 97.1％，P <0.001 RI：30.3％vs 21.9％vs 23.1％，P <0.01 2年NRM：16.1％vs 16.4％vs 26.7％，P <0.01 allo-SCT后第100天急性GvHD II-IV级和II-IV级累积发生率：分别为22.9％（95％CI，20.8-20.5）和9.1（95％CI，7.7-10.6） BuFlu和FLAMSA队列中的急性GvHD：21.1％对 26.9％，P <0.001 慢性GvHD的2年累积发病率：34％（95％CI，31.4-36.5） FLAMSA-TBI与BuFlu比较显示复发率较低（RI）：HR = 0.64（95％CI，0.42-0.98），P = 0.04 FLAMSA-TBI与BuFlu比较显示优越的LFS：HR = 0.72（95％CI，0.49-1.06），P = 0.09 总之，这些发现表明，与移植于CR1或CR2的AML患者中的BuFlu相比，FLAMSA-TBI导致较低的复发发生率。该研究的主要局限性包括其回顾性以及施用GvHD预防的异质性。作者指出，需要进行前瞻性研究以进一步评估FLAMSA方案。 参考 与第一次或第二次完全缓解的AML患者相比，使用FLAMSA-RIC调节的复发率降低与Busulfan / Fludarabine相比 – 来自EBMT的急性白血病工作组的研究。Biol血髓移植。2018年7月12日.DOI：1016 / j.bbmt.2018.07.007。[印刷前的电子版]。 文章来源 http://www.amlglobalportal.com/medical-information/flamsa-versus-busulfan-fludarabine-conditioning-for-acute-myeloid-leukemia-patients