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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