SMILE方案治疗复发难治NK／T细胞淋巴瘤的初步临床报告

 目的　探索SMILE方案治疗NK／T细胞淋巴瘤的疗效和不良反应。方法　2006年11月至2008年2月,5例初治和5例复发NK／T细胞淋巴瘤患者接受SMILE方案（甲氨蝶呤、异环磷酰胺 、左旋门冬酰胺酶、依托泊苷等）化疗。1例患者进一步接受了自体外周血造血干细胞支持下的超大剂量化疗,2例患者进一步接受局部放疗。结果　10例患者中有 8例可以评价疗效,总有效率50 %（4／8）,无完全缓解。其中初治和复发患者有效率均为50 %。主要不良反应为骨髓抑制及氨基转移酶升高,其中Ⅲ～Ⅳ度粒细胞减少占65 %,发热性粒细胞减少占25 %,Ⅲ度氨基转移酶升高占10 %,其他不良反应少见,无治疗相关死亡。26.1 %患者由于严重的不良反应中止治疗。结论　SMILE治疗复发耐药的NK／T细胞淋巴瘤有一定疗效,但不良反应明显,目前尚不能作为复发难治NK／T细胞淋巴瘤的标准一线方案。     

LFP、HLFP方案治疗晚期胃癌的临床观察

目的 观察比较LFP方案和HLFP方案治疗晚期胃癌的近期疗效及不良反应。方法 对61例晚期胃癌患者随机分为LFP组及HLFP组,治疗2个周期后进行疗效及不良反应的评价。结果 LFP组29例,有效率为44.8%,其中复治患者18例,有效率为27.8%。HLFP组32例,有效率为59.4%,其中复治患者22例,有效率为59.1%。2组总疗效无显著性差异。但对复治患者,HLFP组疗效显著高于LFP组。2组不良反应发生率大致相近。不良反应主要为恶心呕吐、口腔粘膜溃疡、骨髓抑制、腹泻等。结论 LFP方案及HLFP方案对晚期胃癌均有较好的疗效,不良反应可耐受。对复治患者,HLFP方案更为理想。     

改良SMILE方案治疗结外NK/T细胞淋巴瘤初探

目的：观察改良SMILE方案治疗结外NK/T细胞淋巴瘤的近期疗效和安全性。方法：2009年6月至2012年3月收治的7例Ⅲ-Ⅳ期患者,3例为初治,4例为复发、难治性患者,均采用改良SMLIE（甲基强的松龙80mg,iv,d2-5;异环磷酰胺（ IFO）1.333g/m2,iv,d2-5,美司钠（ Mesna）300mg/m2,iv,给药0、4、8h,依托泊苷（Vp-16）75mg/m2,iv,d2-5;培门冬酶（Pegasparaginase）2500IU/m2,im,d1;甲氨蝶呤（MTX）1.0g/m2,iv,6h, d5）方案化疗。结果：7例患者共接受SMILE方案化疗31周期,每例至少2个周期,其中,CR 5例,PR 1例,PD 1例,近期总有效率为85.7％,CR率为71.4％。其中,11周期出现Ⅲ﹢Ⅳ度白细胞减少,3周期出现Ⅲ﹢Ⅳ度血红蛋白下降,6周期出现Ⅲ﹢Ⅳ度血小板减少,4周期出现Ⅲ度肝功能损害,对症处理后恢复。结论：改良SMILE方案治疗初治或难治性NK/T细胞淋巴瘤疗效较好,毒性可以耐受,值得临床进一步探讨。     

结直肠癌术后患者采用改良FOLFOX6方案治疗的疗效观察

目的探讨结直肠癌术后患者采用改良FOLFOX6(mFOLFOX6)方案治疗的近期疗效。方法将62例结直肠癌术后患者随机分为采用mFOLFOX6方案治疗的观察组(31例)和采用FOLFOX6方案治疗的对照组(31例),对比分析两组患者的近期疗效和不良反应。结果采用mFOLFOX6方案治疗的观察组患者的胃肠道反应、骨髓毒性、神经毒性等不良反应及在生活质量评分方面均优于对照组,差异有统计学意义(P<0.05);近期疗效与采用FOLFOX6方案治疗的对照组相似。结论 mFOLFOX6方案应用于结直肠癌术后患者不良反应较轻,患者生活质量较高,近期疗效确定。     

以左旋门冬酰胺酶为基础的方案治疗结外鼻型NK/T细胞淋巴瘤36例

 【摘要】 目的 观察以左旋门冬酰胺酶（L-ASP）为基础的方案治疗结外鼻型NK／T细胞淋巴瘤（ENKTL）的近期疗效、远期生存和不良反应。 方法 2008年2月至2011年9月,采用以L-ASP为基础的方案治疗ENKTL 36例。20例Ⅰ、Ⅱ期患者采用VLD方案联合放化疗,16例III、IV期患者行改良SMILE方案化疗,其中4例化疗后接受序贯受累野放疗。 结果 36例患者中35例可评价疗效,完全缓解（CR）率为54.3 %（19／35）,总有效率为68.6 %（24／35）。中位随访13.5个月（3～31个月）,全部患者1年总生存率为82 %,1年无疾病进展生存率为65 %。近期疗效评价有效的患者1年生存率（93 %）和无疾病进展生存率（80 %）均优于对治疗无应答的患者（35 %、33 %）,差异有统计学意义（χ2＝13.909,P ＝ 0.000; χ2＝8.216,P＝ 0.004）。主要不良反应为骨髓抑制,无化疗相关性死亡。 结论 以L-ASP为基础的方案治疗ENKTL显示了较好的疗效,且耐受性好。L-ASP用于一线治疗ENKTL的大型前瞻性临床试验值得开展和深入研究。     

改良TCD方案治疗初治多发性骨髓瘤26例临床观察

目的观察改良TCD方案(小剂量沙利度胺和地塞米松联合环磷酰胺）治疗初治多发性骨髓瘤的临床疗效。方法应用改良TCD方案6周期治疗26例初治多发性骨髓瘤患者,应用血清蛋白电泳、免疫固定电泳、骨髓细胞形态学和β2-微球蛋白评估治疗效果,同时观察药物的不良反应。结果CR 6例,nCR 7例,PR 5例,轻度反应2 例;总有效率69.2%,总反应率76.9%。化疗不良反应轻,无治疗相关性死亡。结论 改良TCD方案治疗初治多发性骨髓瘤疗效较好,不良反应较少,值得临床推广应用。     

改良Hyper—CVAD／MA方案治疗侵袭性淋巴瘤42例

目的评估改良的Hyper-CVAD／MA强化方案治疗侵袭性淋巴瘤患者的有效性和安全性。方法回顾性分析2006年6月至2012年7月收治的42例用改良Hyper-CVAD／MA方案治疗的初治或复治的侵袭性淋巴瘤患者的有效性和安全性。结果19例（45．3％）患者达完全缓解（CR）,13例（31．0％）达部分缓解（PR）,有效率为76．2％（32／42）。1年无病生存（DFS）率和总体生存（OS）率分别为79．2％和83．7％,3年DFS率和OS率分别为65．3％和64．2％。CR率与有无B症状、结外受累、中枢神经系统受累、AnnArbor分期、既往治疗有相关性。主要不良反应包括造血功能受抑、感染、黏膜炎、肝脏、肾脏以及神经系统毒性等。结论改良Hyper—CVAD／MA方案治疗侵袭性淋巴瘤近期疗效满意,治疗相关不良反应可以控制。     

改良DCF分周方案与XELOX方案治疗晚期胃癌疗效的比较

目的探讨改良多西紫杉醇+顺铂+氟尿嘧啶(DCF)分周方案与卡培他滨+奥沙利铂(XELOX)方案治疗晚期胃癌的临床疗效。方法回顾性分析2009年6月至2015年6月间靖江市人民医院肿瘤科收治的98例晚期胃癌患者的临床资料,按治疗方法分为观察组和对照组,每组49例。观察组患者采用改良DCF分周方案治疗,对照组患者采用XELOX方案治疗,比较两组患者治疗后近期疗效、不良反应及生存时间的差异。结果观察组患者近期治疗有效率、疾病进展时间和中位生存时间明显优于对照组(P<0.05)。两组间腹泻、肌肉关节痛、血小板减少和肝功能损害比较差异无统计学意义(P>0.05)。对照组患者手足综合征发生率高,观察组患者恶心呕吐、白细胞减少和脱发发生率较高,差异均有统计学意义(P<0.05)。结论改良DCF分周方案较XELOX方案治疗晚期胃癌的疗效显著,但其不良反应还有待进一步研究。     

吉西他滨联合长春瑞滨方案复治对紫杉醇联合顺铂方案疗效欠佳的晚期非小细胞肺癌24例临床观察

 目的 评价吉西他滨（GEM）联合长春瑞滨（NVB）方案复治对紫衫醇（TAX）联合顺铂（DDP）方案疗效欠佳的晚期非小细胞肺癌（NSCLC）的疗效、生存期及不良反应。方法 24例既往行TAX联合DDP治疗后疗效评价为稳定或进展的晚期NSCLC患者，继续用GEM联合NVB方案治疗，两周期后评价近期疗效和不良反应。结果 24例患者近期有效期29.2 ％，中位生存期28周，一年生存率34.3 %。结论 GEM联合NVB方案复治对TP方案疗效差的NSCLC患者有一定疗效，无交叉耐药性，可使患者病情进展延缓，中位生存期延长，且毒性可耐受。     

CTVP方案治疗侵袭性B细胞非霍奇金淋巴瘤85例临床疗效分析

评估含吡喃阿霉素（THP）及长春地辛（VDS）的CTVP方案治疗非霍奇金淋巴瘤（NHL）的近期疗效、远期生存及不良反应。方法：收集2000年1月至2005年12月间应用CTVP方案治疗的资料完整的侵袭性B细胞NHL患者85例,分析其近期疗效、远期生存及不良反应。结果：85例患者中初治74例,复治11例,全部病例均可评价疗效,一线治疗CR 55.4%,有效率68.9%,临床受益率86.0%,二线治疗有效率45.5%,临床受益率63.6%。随访至2009年12月,中位随访时间为69个月（6～102个月）,1、3、5年生存率分别为82.4%、71.5%和60.7%,中位生存期75个月（6～99个月）,骨髓抑制、胃肠道反应、乏力、外周神经毒性和脱发为主要不良反应。结论：采用含THP和VDS的CTVP方案治疗NHL疗效较好,毒性较低,远期生存率较高,值得临床进一步研究。     

Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are rare, and their standard therapy has not been established. They are Epstein-Barr virus-associated lymphoid malignancies, and tumor cells express P-glycoprotein leading to multidrug resistance of the disease. Patients with stage IV, relapsed or refractory diseases have a dismal prognosis, with survival measured in months only. To develop an efficacious chemotherapeutic regimen, we conducted a dose-escalation feasibility study of a new chemotherapeutic regimen, SMILE, comprising the steroid dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide. The components of SMILE are multidrug resistance-unrelated agents and etoposide. Etoposide shows both in vitro and in vivo efficacy for Epstein-Barr virus-associated lymphoproliferative disorders. Eligible patients had newly diagnosed stage IV, relapsed or refractory diseases after first-line chemotherapy, were 15-69 years of age, and had satisfactory performance scores (0-2). Four dose levels of methotrexate and etoposide were originally planned to be evaluated. At level 1, six patients with extranodal NK/T-cell lymphoma, nasal type, were enrolled. Their disease status was newly diagnosed stage IV (n = 3), first relapse (n = 2), and primary refractory (n = 1). All of the first three patients developed dose-limiting toxicities, and one of them died of sepsis with grade 4 neutropenia. A protocol revision stipulating early granulocyte colony-stimulating factor administration was made. Two out of three additional patients developed dose-limiting toxicities that were all manageable and transient. For the six enrolled patients, the overall response rate was 67% and the complete response rate was 50%. Although its safety and efficacy require further evaluation, we recommend a SMILE chemotherapy dose level of 1 for further clinical studies.     

Toxicity of a Modified PEG-Asparaginase-Based SMILE Regimen Is Comparable to L-Asparaginase-Based SMILE in a Non-Asian Population

IntroductionL-asparaginase–based chemotherapy regimens are effective for treating chemotherapy-resistant natural killer– (NK-) cell neoplasms. To treat these lymphoma subtypes in Asia, where NK/T-cell lymphomas are more prevalent, the NK-Cell Tumor Study Group developed the SMILE regimen, which includes a steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide. In the US however, the only commercially available form of asparaginase is the pegylated form (PEG-asparaginase) which has been incorporated into a modified SMILE (mSMILE). We sought to study the toxicity associated with replacing L-asparaginase with PEG-asparaginase in mSMILE.Patients and MethodsWe retrospectively identified all adult patients treated with the mSMILE chemotherapy regimen in our database at Moffitt Cancer Center (MCC) between December 1, 2009, and July 30, 2021. Patients were included if they were treated with mSMILE irrespective of their underlying diagnosis. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. The rate of toxicity in our mSMILE treatment group was numerically compared to data published in a metanalysis of the SMILE regimen's toxicity (Pokrovsky et al., 2019).ResultsA total of 21 patients were treated with mSMILE at MCC during the 12-year analysis window. Compared to patients receiving the L-asparaginase–based SMILE, patients receiving mSMILE experienced grade 3 or 4 leukopenia less often, with a toxicity rate of 62% (median with SMILE, 85% [95% CI, 74%-95%]); thrombocytopenia, however, was more common, with a toxicity rate of 57% (median with SMILE, 48% [95% CI, 40%-55%]). Other hematological, hepatic and coagulation related toxicities were also reported.ConclusionIn a non-Asian population, the mSMILE regimen with PEG-asparaginase is a safe alternative to the L-asparaginase–based SMILE regimen. There is a comparable risk of hematological toxicity, and no treatment-related mortality was seen in our population.     

异环磷酰胺联合长春瑞滨治疗对铂类耐药的复发和／或转移性鼻咽癌

 目的 探讨异环磷酰胺（IFO）联合长春瑞滨（VRL）治疗对铂类耐药的复发和／或转移的鼻咽癌的疗效和毒副反应。方法 VRL 25 mg／m2，静脉推注，第1，5天；IFO 1 200 mg／m2，静脉滴注3 h，第1 ~ 5天；美斯纳400 mg，静脉推注，IFO开始后0，3，6 h。21 d为1疗程，至少完成2周期作疗效评价。结果 25例患者中，完全缓解（CR）2例，部分缓解（PR）12例，总有效率（CR+PR）为56.0 %，稳定8例，临床获益率（CBR）为88.0 %；疾病进展3例；中位疾病进展时间（TTP）为7.1个月（范围2.0～21.0个月），1年生存率为55 %。主要毒副反应为骨髓抑制和静脉炎。结论 IFO联合VRL治疗对铂类耐药的复发和／或转移的鼻咽癌疗效可靠，毒副反应可耐受。     

IAG方案诱导治疗急性髓系白血病的临床效果观察

目的 探讨小剂量阿糖胞苷和去甲氧柔红霉素联合粒细胞集落刺激因子（G-CSF）组成的IAG预激方案治疗急性髓系白血病（AML）的疗效和患者不良反应.方法 回顾性分析25例AML患者在采用IAG预激方案诱导治疗1个疗程后的临床效果.IAG方案：去甲氧柔红霉素5 mg,静脉滴注,隔天1次,共7～8次;阿糖胞苷每12 h 10 mg/m2,皮下注射,第1天至第14天;G-CSF每天200 μg/m2,皮下注射,用药前一天至第14天.结果 化疗后总有效率80.0％（20/25）,完全缓解（CR）率60.0％（15/25）.初诊17例患者中,9例CR,4例部分缓解（PR）;复发难治患者8例中,6例CR,1例PR.骨髓增生异常综合征（MDS）转化的AML7例中,5例CR,2例PR;≥50岁的11例患者中,8例CR,1例PR.化疗的不良反应主要为骨髓抑制、胃肠道反应、肝肾功能损害;无早期死亡病例.结论 IAG预激方案是治疗AML（包括高危AML）的较有效、安全的方案.     

High-dose cytosine arabinoside and mitoxantrone: preliminary results of a pilot study with sequential application (S-HAM) indicating a high antileukemic activity in refractory acute leukemias

In an attempt to further improve on the encouraging results achieved by high-dose cytosine arabinoside (HD AraC) and mitoxantrone (HAM) in refractory acute leukemias, a timely modified sequential schedule of both drugs was developed (S-HAM) and applied to 13 patients with far advanced acute leukemias, 8 of whom had been treated with the original HAM protocol before. Based on the cell kinetic and pharmacokinetic rationale outlined by Capizzi et al., HD AraC 3 g/m2 was applied every 12 h on days 1 and 2 followed by mitoxantrone 10 mg/m2/day on days 3 and 4. After 3 days without therapy the identical sequence was repeated on days 8 and 9 (HD AraC) and 10 and 11 (mitoxantrone), respectively. Of the 13 patients 9 (69%) achieved a complete remission, 2 were resistant and 2 were early deaths. Six of the 8 patients with prior HAM treatment obtained a further complete remission with S-HAM. In 2 of these patients a longer remission was induced by S-HAM than by the preceding original HAM treatment. Although these data are preliminary and need confirmation on larger numbers of patients, they strongly suggest a high antileukemic activity of the S-HAM protocol which may even be superior to the previously used HAM regimen.     

改良的德国多中心成年人急性淋巴细胞白血病研究组方案临床应用研究

 目的　分析改良的德国多中心成年人急性淋巴细胞白血病研究组（GMALL）方案治疗成年人急性淋巴细胞白血病（ALL）的疗效和安全性。方法　2005年1月至2009年12月共37例新诊断的ALL患者,接受改良的GMALL方案单纯化疗,对其进行回顾性分析,并与同期接受该院常规方案治疗的44例成年ALL患者进行对比分析。结果　改良GMALL方案的累积完全缓解（CR）率为89.2 %（33／37）,1、2、3及4年累积总生存（OS）率分别为77.5 %、48.0 %、40.0 %和40.0 %。主要不良反应为3～4级血液学毒性和感染,不良反应易于控制,治疗相关死亡率低。改良GMALL方案组的OS优于该院常规方案组。结论　改良的GMALL方案治疗成年人ALL疗效满意,不良反应可以耐受,值得临床推广。     

Treatment of metastatic gastric carcinoma with a modified FAMTX chemotherapy regimen

Fifty patients with locally far advanced or metastasizing gastric carcinoma were treated with 5-fluorouracil, adriamycin and methotrexate using a slightly modified FAMTX protocol. Complete remission was achieved in four (8%) patients, confirmed operatively, partial remission in 13 (26%) patients, two of these going into complete remission after operative removal of residual tumor. Median duration of remission for the six patients in complete remission was 21 months, for those in partial remission five months. Median survival for all 50 patients was seven months, for those in complete and partial remission 12 months, and for those without remission four months. These results indicate the possibility of a further improvement of treatment results in patients with metastasizing gastric carcinoma using this protocol of combined operation and chemotherapy.