CN117320704A - 血癌的治疗方法 - Google Patents
血癌的治疗方法 Download PDFInfo
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- CN117320704A CN117320704A CN202280034828.1A CN202280034828A CN117320704A CN 117320704 A CN117320704 A CN 117320704A CN 202280034828 A CN202280034828 A CN 202280034828A CN 117320704 A CN117320704 A CN 117320704A
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- leukemia
- lymphoma
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- blood cancer
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Abstract
本发明提供了一种用于治疗患有骨癌或血癌或转移至骨的癌症的有此需要的受试者的方法,该方法包括向该受试者施用有效量的羟基脲甲基酰基富烯。
Description
相关申请的交叉引用
本申请要求于2021年5月3日提交的美国临时专利申请63/183,519号的权益,该美国临时专利申请以引用的方式全文并入本文。
技术领域
本申请涉及癌症治疗,特别是涉及血癌的治疗方法。
背景技术
血癌会影响血细胞和骨髓,骨髓是骨骼中制造血细胞的海绵状组织。这些癌症改变了血细胞的行为方式及其工作状况。有三种主要类型的血癌:白血病、淋巴瘤和骨髓瘤。这些癌症导致骨髓和淋巴系统产生有缺陷的血细胞。它们都会影响不同亚型的血细胞,并且它们以不同的方式发挥作用。如果及早发现,血癌可通过化疗、靶向治疗或手术来治疗,这将是理想的选择,特别是如果肿瘤和癌细胞没有扩散并且可被干净地去除。
血癌预后基于亚型和其他因素而异,包括整体健康状况、年龄和对治疗的应答。虽然在血癌治疗领域已经取得了很大的进步,但是血癌的总体5年存活率为70%。此外,一些患者尤其是老年患者无法耐受高强度化疗或干细胞移植手术,留给他们的癌症治疗选择非常少。对标准癌症疗法的耐药性或复发也很常见。例如,50%接受伊马替尼治疗的慢性骨髓性白血病(CML)患者最终会产生耐药性或不耐受。一些血癌诸如套细胞淋巴瘤是不可治愈的,这意味着患者最终会从所有可用的治疗中复发并耗尽所有选择。还有罕见的血癌,其治疗仍然非常具有挑战性。例如,双重打击淋巴瘤没有既定护理标准,并且中位生存时间仅为5个月。
因此,需要用于血癌(包括双重打击淋巴瘤)的改进的治疗。
发明内容
本申请的一个方面包括一种用于治疗患有血癌的患者的方法,其中将羟基脲甲基酰基富烯或其盐以治疗有效量施用于患有血癌的有此需要的受试者。血癌可包括套细胞淋巴瘤(MCL)、双重打击淋巴瘤(DHL)、伯基特淋巴瘤、间变性大细胞淋巴瘤(ALCL)、多发性骨髓瘤(MM)、急性骨髓性白血病(AML)、急性淋巴细胞白血病(ALL)和慢性骨髓性白血病(CML)。
另一个方面包括:一种药物组合物,具有有效量的羟基脲甲基酰基富烯或其药学上可接受的盐;以及(b)至少一种药学上可接受的载体。一种羟基脲甲基酰基富烯,标记为化合物1,如下所示:
另一个方面包括施用第二抗癌剂,该第二抗癌剂可包括DNA损伤剂、糖皮质激素、免疫调节药物(IMiD)、BCL2抑制剂、布鲁顿氏酪氨酸激酶抑制剂、PARP抑制剂和/或蛋白酶体抑制剂。
另一个方面包括以口服、局部、鼻内、全身、静脉内、皮下、腹膜内、皮内、眼内、离子电渗、经粘膜或肌内方式施用羟基脲甲基酰基富烯来治疗血癌。
另一个方面包括一种方法,其中血癌是淋巴瘤或骨髓瘤的方法。
另一个方面包括一种方法,其中血癌是套细胞淋巴瘤(MCL)、双重打击淋巴瘤(DHL)、伯基特淋巴瘤、间变性大细胞淋巴瘤(ALCL)或多发性骨髓瘤(MM)。
另一个方面包括一种方法,其中将羟基脲甲基酰基富烯与向有此需要的受试者施用第二抗癌剂联合施用。
另一个方面包括一种方法,其中第二抗癌剂选自DNA损伤剂、糖皮质激素、免疫调节药物(IMiD)、BCL2抑制剂、布鲁顿氏酪氨酸激酶抑制剂、螺甾内酯、PARP抑制剂和/或蛋白酶体抑制剂。
另一个方面包括一种方法,其中有此需要的受试者同时用另一种疗法进行治疗,以治疗急性骨髓性白血病、急性淋巴细胞白血病、骨髓增生异常综合征、骨髓增生性疾病或慢性骨髓性白血病。
另一个方面包括一种方法,其中有此需要的受试者是人。
另一个方面包括一种方法,其中血癌是套细胞淋巴瘤(MCL)、双重打击淋巴瘤(DHL)、伯基特淋巴瘤、间变性大细胞淋巴瘤(ALCL)、多发性骨髓瘤(MM)、急性骨髓性白血病(AML)、急性淋巴细胞白血病(ALL)和/或慢性骨髓性白血病(CML)。
另一个方面包括用于治疗患有血癌或转移至骨的癌症的有此需要的受试者的方法。该方法包括向受试者施用有效量的羟基脲甲基酰基富烯或化合物1。
附图说明
图1显示了使用一组细胞系证明化合物1的细胞毒性活性的有效性和选择性的表。
具体实施方式
本申请包括一种用于治疗患有血癌的患者的方法,其中将羟基脲甲基酰基富烯或其盐以治疗有效量施用于患有血癌的受试者。在某些实施方案中,血癌可以是套细胞淋巴瘤(MCL)、双重打击淋巴瘤(DHL)、伯基特淋巴瘤、间变性大细胞淋巴瘤(ALCL)、多发性骨髓瘤(MM)、急性骨髓性白血病(AML)、急性淋巴细胞白血病(ALL)和/或慢性骨髓性白血病(CML)。术语“血癌”可指包括异常细胞生长并有可能扩散到身体其他部位的疾病。此类血癌包括套细胞淋巴瘤(MCL)、双重打击淋巴瘤(DHL)、伯基特淋巴瘤、间变性大细胞淋巴瘤(ALCL)、多发性骨髓瘤(MM)、急性骨髓性白血病(AML)、急性淋巴细胞白血病(ALL)和慢性骨髓性白血病(CML)。
在一个具体的实施方案中,羟基脲甲基酰基富烯(由Lantern Pharma Inc.命名为LP-284,其使光正向偏移(具有正旋光度))的结构如下所示:
在另一个具体的实施方案中,羟基脲甲基酰基富烯(由Lantern Pharma Inc.命名为LP-184,其使光正向偏移(具有负旋光度))的结构如下所示:
一个实施方案包括具有式I的化合物1或其药学上可接受的盐用于治疗有此需要的受试者的癌症、特别是用于治疗血癌的方法和用途。
在一个实施方案中,“有此需要的受试者”是患有血癌的受试者。例如,白血病是急性骨髓性白血病、急性淋巴细胞白血病、急性混合细胞白血病、骨髓增生异常综合征、骨髓增生性疾病或慢性骨髓性白血病。在某些实施方案中,受试者是由于年龄或并发疾病而不能接受其他疗法来治疗癌症的受试者。在某些实施方案中,受试者为至少20岁、或至少30岁、或至少40岁、或至少50岁、或至少60岁、或至少65岁、或至少70岁或更老。
在一些实施方案中,有此需要的受试者接收至少一种先前疗法来治疗血癌,诸如套细胞淋巴瘤(MCL)、双重打击淋巴瘤(DHL)、伯基特淋巴瘤、间变性大细胞淋巴瘤(ALCL)、多发性骨髓瘤(MM)、急性骨髓性白血病(AML)、急性淋巴细胞白血病(ALL)和慢性骨髓性白血病(CML)。在一些实施方案中,受试者患有耐药性或难治性血癌。耐药性或难治性血癌定义为在开始时对治疗有耐药性或在治疗期间或之后获得耐药性。
在一些实施方案中,治疗有效量的羟基脲甲基-酰基富烯(例如,化合物1)或其药学上可接受的盐选自由以下组成的组:0.5mg/天、1mg/天、2.5mg/天、5mg/天、10mg/天、20mg/天、30mg/天、60mg/天、90mg/天、120mg/天、150mg/天、180mg/天、210mg/天、240mg/天、270mg/天、300mg/天、360mg/天、400mg/天、440mg/天、480mg/天、520mg/天、580mg/天、600mg/天、620mg/天、640mg/天、680mg/天和720mg/天。
羟基脲甲基酰基富烯或其盐可包括药学上可接受的组分。本文所用的术语“药学上可接受的”是指在合理的医学判断范围内适于与人和其他哺乳动物的组织接触而没有过度毒性、刺激性、变应性应答等并且与合理的效益/风险比相称的组分。例如,此类常规无毒盐包括但不限于衍生自无机酸和有机酸的那些无毒盐,这些无机酸和有机酸选自2-乙酰氧基苯甲酸、2-羟基乙烷磺酸、乙酸、抗坏血酸、苯磺酸、苯甲酸、碳酸氢酸、碳酸、柠檬酸、依地酸、乙烷二磺酸、1,2-乙烷磺酸、富马酸、葡庚糖酸、葡萄糖酸、谷氨酸、乙醇酸、乙醇酰对氨基苯胂酸、己基间苯二酚酸、海巴明酸(hydrabamic)、氢溴酸、盐酸、氢碘酸、羟基马来酸、羟基萘酸、羟乙磺酸、乳酸、乳糖酸、月桂基磺酸、马来酸、苹果酸、扁桃酸、甲磺酸、萘磺酸(napsylic)、硝酸、草酸、双羟萘酸、泛酸、苯乙酸、磷酸、聚半乳糖醛酸、丙酸、水杨酸、硬脂酸、次乙酸(subacetic)、琥珀酸、氨基磺酸、磺胺酸、硫酸、单宁酸、酒石酸、甲苯磺酸,以及常见的氨基酸,例如甘氨酸、丙氨酸、苯丙氨酸、精氨酸等。
在一个实施例中,可在施用一种或多种化疗剂之前、同时或之后施用羟基脲甲基酰基富烯或其盐。
使细胞与羟基脲甲基酰基富烯或化合物1或其药学上可接受的盐、前药、代谢物或溶剂化物接触可选择性地诱导或活化癌细胞中的细胞死亡。向有此需要的受试者施用化合物1或其药学上可接受的盐、前药、代谢物或溶剂化物可选择性地诱导或活化癌细胞中的细胞死亡。使细胞与本文公开的化合物或其药学上可接受的盐、前药、代谢物或溶剂化物接触可选择性地诱导受细胞增殖性疾病影响的一个或多个细胞中的细胞死亡。
在一个实施方案中,有此需要的受试者可用化合物1或本文公开的化合物作为单一疗法进行治疗。“单一疗法”是指向有此需要的受试者施用单一活性或治疗性化合物。单一疗法可包括施用治疗有效量的单一活性化合物。
在另一个实施方案中,上述治疗方法中的任何治疗方法包括对患者共同施用一种或多种第二治疗剂的另外的步骤。可从已知可用于与羟基脲甲基酰基富烯或其盐共同施用的任何第二治疗剂中选择药剂组合或第二治疗剂。第二治疗剂的选择可取决于待治疗的特定疾病或病症。可在本申请的方法中采用的第二治疗剂的实施例是上面列出的用于包括本发明化合物和第二治疗剂的组合组合物中的那些。具体的化疗剂包括但不限于环磷酰胺、氟尿嘧啶(或5-氟尿嘧啶或5-FU)、甲氨蝶呤、依达曲沙(10-乙基-10-脱氮-氨基蝶呤)、噻替哌、卡铂、顺铂、紫杉烷、紫杉醇、蛋白结合紫杉醇、多西他赛、长春瑞滨、他莫昔芬、雷洛昔芬、托瑞米芬、氟维司群、吉西他滨、伊立替康、伊沙匹隆、替莫唑胺、托泊替康、长春新碱、长春碱、艾日布林、丝裂霉素、卡培他滨、阿那曲唑、依西美坦、来曲唑、亮丙瑞林、阿巴瑞克、布舍瑞林、戈舍瑞林、醋酸甲地孕酮、利塞膦酸盐、帕米膦酸盐、伊班膦酸盐、阿仑膦酸盐、狄诺塞麦、唑来膦酸盐、曲妥珠单抗、泰克布、蒽环类药物(例如柔红霉素和多柔比星)、克拉屈滨、米哚妥林、贝伐单抗、奥沙利铂、美法仑、依托泊苷、氮芥、博莱霉素、微管毒物、番荔枝内酯、苯丁酸氮芥、异环磷酰胺、链脲佐菌素、卡莫司汀、洛莫司汀、白消安、达卡巴嗪、替莫唑胺、六甲蜜胺、6-巯基嘌呤(6-MP)、阿糖胞苷、氟尿苷、氟达拉滨、羟基脲、培美曲塞、表柔比星、伊达比星、SN-38、ARC、NPC、喜树碱、9-硝基喜树碱、9-氨基喜树碱、rubifen、吉马替康、替尼泊苷、二氟替康、BN80927、DX-8951f、MAG-CPT、amsacnne、磷酸依托泊苷、替尼泊苷、阿扎胞苷(Vidaza)、地西他滨、accatin III、10-脱乙酰基紫杉醇、7-木糖基-10-脱乙酰基紫杉醇、三尖杉宁碱、10-脱乙酰基-7-表紫杉醇、7-表紫杉醇、10-脱乙酰基巴卡丁III、10-脱乙酰基三尖杉宁碱、链脲佐菌素、尼莫司汀、雷莫司汀、苯达莫司汀、乌拉莫司汀、雌莫司汀、甘露舒凡、喜树碱、依喜替康、勒托替康、片螺素D9-氨基喜树碱、安吖啶、玫瑰树碱、金精三羧酸、HU-331或它们的组合。
在另一个实施方案中,第二治疗剂是一种或多种选自喜树碱衍生物、紫杉醇、多西他赛、埃博霉素B、5-FU、吉西他滨、奥沙利铂、顺铂、卡铂、美法仑、达卡巴嗪、替莫唑胺、阿霉素、伊马替尼、埃罗替尼、贝伐单抗、西妥昔单抗和Raf激酶抑制剂的化疗剂。
在另一个实施方案中,第二治疗剂是一种或多种选自紫杉醇或顺铂的化疗剂。
如本领域技术人员所认识到的,治疗有效剂量可变化,这取决于所治疗的疾病、疾病的严重程度、施用途径、患者的年龄和总体健康状况、赋形剂的使用、与其他治疗性治疗共同使用的可能性(诸如使用其他药剂)以及治疗医师的判断。例如,选择有效剂量的指南可通过参考羟基脲甲基酰基富烯的处方信息或其期刊讨论来确定。
本文所用的术语“有效量”是指减轻疾病或病症的至少一种或多种症状所需的药剂的量,并且涉及足以提供所需效果的药物组合物的量。因此,术语“治疗有效量”是指当施用于典型受试者时足以提供特定效果的药剂的量。在各种情况下,本文所用的有效量还将包括足以延缓疾病症状的发展、改变疾病症状的进程(例如但不限于,减缓疾病症状的进展)或逆转疾病症状的量。因此,指定确切的“有效量”通常是不可行的。然而,对于任何给定情况,本领域普通技术人员仅使用常规实验即可确定适当的“有效量”。
因此,对于任何化合物,治疗有效量最初可在细胞培养测定(例如,肿瘤细胞的测定)中或在动物模型(通常是大鼠、小鼠、兔、狗或猪)中估计。动物模型也可用于确定合适的浓度范围和给药途径。然后,这样的信息可用于确定对人有用的剂量和给药途径。治疗/预防功效和毒性可通过细胞培养物或实验动物中的标准药学程序来确定,例如ED50(对50%的群体治疗有效的剂量)和LD50(对50%的群体致死的剂量)。毒性效果和治疗效果之间的剂量比是治疗指数,并且它可表示为比率LD50/ED50。表现出大的治疗指数的药物组合物是优选的。剂量可以在此范围内变化,这取决于所采用的剂型、患者的敏感性和给药途径。对于给定情况的治疗有效量可通过临床医生的技能和判断范围内的常规实验来确定。在一个方面,待治疗的疾病或病症是CLL。在另一个方面,待治疗的疾病或病症是AML。
根据本文所述方法施用药剂的剂量范围取决于例如药剂的形式、其效力以及本文所述病症的症状、标志物或指标需要降低的程度,例如肿瘤生长所需的百分比减少。剂量不应太大,以免引起不良副作用。通常,剂量将随着患者的年龄、病症和性别而变化,并且可由本领域技术人员确定。在出现任何并发症的情况下,剂量也可由个体医师调整。
熟练的临床医生可确定本文所述药剂在例如本文所述病症的治疗中的功效,或诱导如本文所述应答(例如血癌)的功效。然而,治疗被认为是“有效的治疗”,如本文所使用的术语,如果本文所述病症的一种或多种体征或症状以有益的方式改变,其他临床上可接受的症状得到改善,或甚至减轻,或在根据本文所述方法治疗后,例如至少10%诱导了期望应答。例如,可通过测量根据本文所述方法治疗的病症的标志物、指标、症状和/或发生率,或任何其他合适的可测量参数,例如肿瘤大小和/或生长速率,来评估疗效。功效还可通过住院治疗或需要药物干预(即疾病的进展停止)来评估个体恶化的失败来测量功效。测量这些指标的方法是本领域技术人员已知的和/或在本文中有所描述。治疗包括对个体或动物(一些非限制性实施例包括人或动物)疾病的任何治疗,并且包括:(1)抑制疾病,例如防止症状恶化(例如疼痛或炎症);或(2)减轻疾病的严重程度,例如,使症状好转。用于治疗疾病的有效量是指当施用有需要的受试者时,足以导致对所述疾病进行有效治疗的量,如所述术语在本文中所定义的。药剂的功效可通过评估病症或期望应答的物理指标来确定。本领域技术人员完全有能力通过测量此类参数中的任何一个参数或参数的任何组合来监测施用和/或治疗的功效。当使用实验动物模型时,当观察到标志物(例如肿瘤大小和/或生长率)的统计学显著变化时,证明治疗的功效。
所使用的术语“治疗”包括治疗性治疗和预防性治疗(降低发生的可能性)。这两个术语都表示降低、抑制、减弱、减少、阻止或稳定疾病(例如,本文描述的疾病或病症)的发展或进展、减轻疾病的严重性或改善与疾病相关的症状。
治疗癌症可使肿瘤大小减小。肿瘤大小的减小也可称为“肿瘤消退”。治疗之后,肿瘤大小相对于其治疗前的大小减小5%或更多;或者肿瘤大小减小10%或更多;或者减小20%或更多;或者减小30%或更多;或者减小40%或更多;或者减小50%或更多;并且/或者减小大于75%或更多。肿瘤大小可通过任何可重复的测量手段来测量。肿瘤大小可作为肿瘤的直径来测量。
治疗癌症可使肿瘤体积减小。治疗之后,肿瘤体积可相对于其治疗之前的大小减小5%或更多;肿瘤体积可减小10%或更多;减小20%或更多;减小30%或更多;减小40%或更多;减小50%或更多;或者减小大于75%或更多。肿瘤体积可通过任何可重复的测量手段来测量。
治疗癌症使肿瘤数量减少。治疗之后,肿瘤数量可相对于治疗之前的数量减少5%或更多。另外,肿瘤数量可减少10%或更多;减少20%或更多;减少30%或更多;减少40%或更多;减少50%或更多或减少大于75%。肿瘤数量可通过任何可重复的测量手段来测量。肿瘤数量可通过计数肉眼可见的或在指定放大倍数下可见的肿瘤来测量。
治疗癌症可使经治疗的受试者群体与仅接受载体的群体相比,平均生存时间增加。平均生存时间可增加超过30天、超过60天、超过90天以及超过120天。群体平均生存时间的增加可通过任何可重复的手段测量。
治疗癌症可使经治疗的受试者群体与未治疗的受试者群体相比,平均生存时间增加。优选地,平均生存时间增加超过30天;更优选地,超过60天;更优选地,超过90天;以及最优选地,超过120天。群体平均生存时间的增加可通过任何可重复的手段测量。群体的平均生存时间的增加可例如通过计算群体在开始用活性化合物治疗后的平均生存期来测量。群体的平均生存时间的增加也可例如通过计算群体在完成用活性化合物的第一轮治疗后的平均生存期来测量。
治疗癌症可使经治疗的受试者群体与接受用不是本发明的化合物或其药学上可接受的盐、前药、代谢物、类似物或衍生物的药物进行的单一疗法的群体相比,平均生存时间增加。平均生存时间可增加超过30天、超过60天、超过90天以及超过120天。群体平均生存时间的增加可通过任何可重复的手段测量。群体的平均生存时间的增加可例如通过计算群体在开始用活性化合物治疗后的平均生存期来测量。
治疗癌症可使经治疗的受试者群体与仅接受载体的群体相比,死亡率降低。经治疗的受试者群体的死亡率的降低可通过任何可重复的手段测量。群体死亡率的降低可例如通过计算群体在开始用活性化合物治疗后每单位时间疾病相关死亡的平均数量来测量。群体死亡率的降低还可例如通过计算群体在完成用活性化合物的第一轮治疗后每单位时间疾病相关死亡的平均数量来测量。
治疗癌症可使肿瘤生长速率降低。治疗之后,肿瘤生长速率相对于治疗之前的数量降低至少5%。此外,肿瘤生长速率可降低至少10%、降低至少20%、降低至少30%、降低至少40%、降低至少50%、降低至少50%或者降低至少75%。肿瘤生长速率可通过任何可重复的测量手段来测量。肿瘤生长速率可根据每单位时间肿瘤直径的变化来测量。
治疗癌症可使肿瘤再生减少。肿瘤再生可通过任何可重复的测量手段来测量。肿瘤再生例如通过在治疗后先前肿瘤缩小之后测量肿瘤直径的增加来测量。治疗停止后肿瘤不再复发表明肿瘤再生减少。
治疗或预防癌症可使具有异常外观或形态的细胞的数量或比例降低。异常的细胞形态可通过显微镜测量,例如使用倒置组织培养显微镜测量。异常的细胞形态可呈现核多态性的形式。
治疗癌症或细胞增殖性疾病可导致细胞死亡,而细胞死亡会导致群体中细胞数量减少至少10%。细胞死亡是指减少至少20%;更优选地,减少至少30%、减少至少40%、减少至少50%或减少至少75%。群体中的细胞数量可通过任何可重复的手段测量。
治疗可包括使用一种或多种生物标志物。该生物标志物可低于、高于或等于健康人中那些标志物的水平。
实施例
为了更有效地理解本文公开的公开内容,下面提供了实施例。应当理解,这些实施例仅用于说明的目的,不应被解释为以任何方式限制本公开。
实施例1
化合物1的合成可见于标题为“ILLUDIN ANALOGS,USES THEREOF,AND METHODSFOR SYNTHESIZING THE SAME”的WO/2020/051222。
实施例2
使用一组人血细胞系评估化合物1(具有正光学手性)的敏感性和选择性。本实施例中使用的细胞系如下所示并绘制在图1中。根据细胞系24小时的倍增时间,将细胞以不同细胞数/孔接种到96孔板中。然后用5~8种不同剂量的化合物1和DMSO载体对照处理这些细胞。再孵育48或72小时后,通过磺酰罗丹明B(SRB)测定(48小时)或Promega CelltiterFluor细胞活力测定(72小时)测量活细胞/孔的数量。然后基于不同化合物1剂量下的归一化细胞计数来计算IC50值。通过细胞活力测量来确定抗增殖活性。表1显示了化合物1在多种白血病和淋巴瘤中的敏感性。表1显示了研究的细节。
表1
前述实施例和优选实施方案的描述应当被认为是说明性的,而不是限制如权利要求所限定的本发明。
容易理解的是,在不脱离如权利要求书中所阐述的本发明的情况下,可利用上述特征的多种变化和组合。这种变化不被视为脱离本发明的范围,并且所有这种变化都旨在包括在以下权利要求的范围内。本文所引用的所有参考文均以引用的方式全文并入。
Claims (20)
1.一种用于治疗患有血癌的有此需要的受试者的方法,所述方法包括向所述受试者施用有效量的具有以下结构的化合物:
2.根据权利要求1所述的方法,其中所治疗的血癌是白血病。
3.根据权利要求1所述的方法,其中所治疗的血癌是套细胞淋巴瘤。
4.根据权利要求1所述的方法,其中所治疗的血癌是双重打击淋巴瘤。
5.根据权利要求1所述的方法,其中所治疗的血癌是急性白血病,所述急性白血病是复发性或难治性急性白血病。
6.根据权利要求1所述的方法,其中所治疗的血癌是急性白血病,所述急性白血病是复发性或难治性急性淋巴细胞白血病(ALL)或复发性或难治性急性骨髓性白血病(AML)。
7.根据权利要求1所述的方法,其中所述血癌是淋巴瘤或骨髓瘤。
8.根据权利要求1所述的方法,其中所述血癌是套细胞淋巴瘤(MCL)、双重打击淋巴瘤(DHL)、伯基特淋巴瘤、间变性大细胞淋巴瘤(ALCL)、多发性骨髓瘤(MM)。
9.根据权利要求1所述的方法,与向所述受试者施用第二抗癌剂联合。
10.根据权利要求9所述的方法,其中所述第二抗癌剂选自由以下组成的组:DNA损伤剂、糖皮质激素、免疫调节药物(IMiD)、BCL2抑制剂、布鲁顿氏酪氨酸激酶抑制剂、螺甾内酯、PARP抑制剂和/或蛋白酶体抑制剂。
11.根据权利要求1所述的方法,其中有此需要的所述受试者同时用另一种疗法进行治疗,以治疗急性骨髓性白血病、急性淋巴细胞白血病、骨髓增生异常综合征、骨髓增生性疾病或慢性骨髓性白血病。
12.根据权利要求1所述的方法,其中有此需要的所述受试者是人。
13.根据权利要求1所述的方法,其中所述化合物以口服、局部、鼻内、全身、静脉内、皮下、腹膜内、皮内、眼内、离子电渗、经粘膜或肌内方式施用。
14.根据权利要求1所述的方法,其中所述施用包括静脉内或腹膜内注射。
15.根据权利要求1所述的方法,其中所述血癌选自由以下组成的组:套细胞淋巴瘤(MCL)、双重打击淋巴瘤(DHL)、伯基特淋巴瘤、间变性大细胞淋巴瘤(ALCL)、多发性骨髓瘤(MM)、急性骨髓性白血病(AML)、急性淋巴细胞白血病(ALL)和慢性骨髓性白血病(CML)。
16.一种用于治疗患有血癌的有此需要的受试者的方法,所述方法包括向所述受试者施用有效量的羟基脲甲基酰基富烯。
17.根据权利要求16所述的方法,所述羟基脲甲基酰基富烯具有以下结构:
18.根据权利要求16所述的方法,其中有此需要的所述受试者同时用另一种疗法进行治疗,以治疗套细胞淋巴瘤(MCL)、双重打击淋巴瘤(DHL)、伯基特淋巴瘤、间变性大细胞淋巴瘤(ALCL)、多发性骨髓瘤(MM)、急性骨髓性白血病(AML)、急性淋巴细胞白血病(ALL)和慢性骨髓性白血病(CML)。
19.根据权利要求16所述的方法,其中所治疗的血癌是套细胞淋巴瘤。
20.根据权利要求16所述的方法,其中所治疗的血癌是双重打击淋巴瘤。
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