The combined effect of IDA and glutaraldehyde on the properties of human erythrocytes

The effect of IDA and glutaraldehyde on the properties of human erythrocytes was examined by Electron Spin Resonance spectroscopy and fluorescence measurements. In this study glutaraldehyde was used as the agent linking the drug to the erythrocyte membrane. We have demonstrated that idarubicin (IDA) alone caused only negligible changes of the membrane fluidity. When IDA preincubated erythrocytes were treated with glutaraldehyde, the alterations in the fluidity were observed in the polar parts as well as in the deeper regions of the cell membrane. The incorporation of drug and glutaraldehyde into human erythrocytes also caused conformational alterations of membrane cytoskeletal proteins and changes in the internal viscosity of the cells. Our data suggest that glutaraldehyde in idarubicin-pretreated erythrocytes may potentiate the drug toxicity leading to significant perturbations in the organization of the plasma membrane lipids and proteins.     

Phase I trial of Idarubicin (4-demethoxydaunorubicin) in adult acute leukemia

Summary Idarubicin (IDR) is a new analog of Daunorubicin (DNR) selected for clinical trials because of its outstanding activity in experimental leukemias of mice and in several experimental models when compared to DNR and Doxorubicin. This Phase I trial was designed to determine the maximal tolerated dose in adult patients with acute leukemia refractory to prior treatment, using intravenously (I.V.) daily treatments for 5 consecutive days.Eleven patients were entered in this study. The initial dose of IDR was 4 mg/m²/d × 5 I.V. The highest dose given was 8 mg/m²/d × 5 I.V. Dose limiting toxicity were gastrointestinal side effects at the 8 mg/m²/d × 5 level (mucositis-diarrhea). Antileukemic activity has been detected in acute non-lymphoblastic leukemia not pretreated with anthracyclines. For Phase II adult leukemia studies using this schedule, it is recommended that the IDR dose should be 7 mg/m²/d.     

去甲氧柔红霉素联合阿糖胞苷治疗急性髓系白血病的临床疗效

目的：探讨急性髓系白血病患者采用去甲氧柔红霉素联合阿糖胞苷治疗的临床疗效。方法70例急性髓系白血病患者按照随机数字表法分为对照组与治疗组,各35例。对照组采用柔红霉素治疗。治疗组采用去甲氧柔红霉素治疗。比较2组临床疗效、生存质量、毒副作用。结果治疗后治疗组治疗有效率为45．71％（16／35）与对照组[40．00％（14／35）]比较P＞0．05;治疗组治疗获益率为57．14％（20／35）,明显高于对照组[45．71％（16／35）]（P＜0．05）;2组患者KPS改善率比较（P＜0．05）。治疗组治疗期间不良反应发生率为48．57％（17／35）明显低于对照组[77．14％（27／35）]（P＜0．05）。结论去甲氧柔红霉素联合阿糖胞苷治疗急性髓系白血病患者的临床总体疗效较好,且显著改善患者生存质量,减少不良反应,值得推广应用。     

减低剂量去甲氧柔红霉素或高三尖杉酯碱联合阿糖胞苷治疗初治急性髓系白血病效果观察

目的 比较减低剂量去甲氧柔红霉素(IDA)联合阿糖胞苷(Ara-C)(IA)与减低剂量高三尖杉酯碱(HHT)联合Ara-C(HA)两种化疗方案对初治急性髓系白血病(AML)的诱导缓解疗效及患者不良反应.方法 回顾性分析2012年1月1日至2015年6月30日收治的采用减低剂量IA方案(低剂量IA组)或减低剂量HA方案(低剂量HA组)治疗的初治AML(除外急性早幼粒细胞白血病)患者的病例资料,比较两组患者的疗效及不良反应.结果 诱导治疗2个疗程后,低剂量IA组67例患者中46例达完全缓解(CR),CR率为68.7％,低剂量HA组20例患者中8例达CR,CR率为40.0％,两组差异有统计学意义(x 2=5.372,P=0.020).两组总有效率(ORR)分别为77.6％(52/67)和60.0％(12/20),差异无统计学意义(P＞0.05).两组患者的血液学不良反应主要均为骨髓抑制,但除中性粒细胞绝对计数＜1×109/L的中位持续时间差异有统计学意义(Z=-3.023,P=0.003)外,其余差异均无统计学意义(均P＞ 0.05);非血液学不良反应两组差异均无统计学意义(均P＞0.05).结论 对于初治AML患者,低剂量IA方案的疗效优于低剂量HA方案,但不良反应较低剂量HA方案严重.     

去甲氧柔红霉素联合预激方案治疗初发老年急性髓细胞白血病的疗效分析

目的探讨去甲氧柔红霉素（IDA）联合预激方案（IDA+CAG）治疗初发老年急性髓细胞白血病（AML）的疗效及不良反应。方法回顾性分析2002年1月至2011年1月本院收治的138例初发老年AML患者的临床资料,分为治疗组（68例）和对照组（70例）。治疗组采用IDA-CAG方案：IDA 3 mg/m2 d1~2;粒细胞集落刺激因子（G-CSF）300μg d2、150μg d3~14,阿克拉霉素10 mg/d d3～5,阿糖胞苷15 mg/m2、q 12 h d3～14;白细胞计数（WBC）＜1.0×109/L或骨髓增生极度减低时停药。对照组采用羟基脲加最佳支持治疗方案：羟基脲1.5 g bid,WBC＜10.0×109/L停药,并给予血液制品、抗感染等支持治疗。观察两组患者疾病完全缓解（CR）、部分缓解（PR）、稳定（SD）、进展（PD）例数及总生存（OS）、无病生存（DFS）时间和不良反应。结果治疗组CR 5例（7.3%）,PR 35例（51.5%）,SD17例（25.0%）,PD 11例（16.2%）,总有效率58.8%,疾病控制率83.8%;中位OS 14个月,中位DFS 12个月。对照组SD 60例（85.7%）,PD 10例（14.3%）,疾病控制率85.7%;中位OS 6个月,中位DFS 0个月。主要不良反应为感染、中性粒细胞下降、贫血和胃肠道反应,治疗组≥Ⅲ度呕吐5例（7.4%）,≥Ⅲ度血液学毒性27例（39.7%）;对照组≥Ⅲ度呕吐0（0）,≥Ⅲ度血液学毒性12例（17.1%）。结论 IDA联合CAG方案疗效好,药物副作用少,并发症相对较少,耐受性较好。明显提高患者OS及DFS。     

Is there an optimal adjunct therapy to traditional cytotoxic induction?

The traditional cytotoxic induction regimen for acute myeloid leukemia (AML) is seven days of standard-dose cytarabine and three days of an anthracycline antibiotic (such as daunorubicin or idarubicin), commonly known as “7 + 3.” Many studies have been conducted to find an additional agent that might improve efficacy. Data from select studies has shown, in certain populations, benefit to adding cladribine, clofarabine and lomustine to a traditional backbone. For mutation-based chemotherapy regimens, midostaurin with 7 + 3 is the current standard of care for FLT3-mutant, younger AML patients. As we learn more about the synergism of molecular agents and traditional anti-cancer treatments, we can hopefully develop novel regimens without abandoning some of the benefits of these mutation agnostic historical therapies.     

含去甲氧基柔红霉素化疗方案治疗成人初发急性淋巴细胞白血病疗效观察

目的观察含去甲氧柔红霉素的联合化疗方案治疗成人初发急性淋巴细胞白血病的疗效和不良反应。方法15例成人初发急性淋巴细胞白血病患者均给予VICP方案（长春新碱2mg／d,第1,8,15,21天;IDA10mg／d,第1～3天,第15～17天;环磷酰胺600mg／d,第1,15天,第22—28天;泼尼松40～60mg／d,第1—28天）。结果15例患者中,第1疗程获CR12例,CR率80％;PR1例,总有效率86．7％;NR2例。结论含去甲氧柔红霉素的联合化疗方案治疗成人初发急性淋巴细胞白血病疗效好,不良反应轻。     

Effects of 1-Methyl-3-propyl-7-butylxanthine (MPBX) on Idarubicin-induced Antitumor Activity and Bone Marrow Suppression

The effects of 1-methyl-3-propyl-7-butylxanthine (MPBX), a xanthine derivative, on idarubicin (IDA)-induced antitumor activity against P388 leukemia cells (P388) and bone marrow suppression were examined. In P388 tumor-bearing mice, the combination of MPBX with IDA increased the antitumor activity of IDA. The IDA concentration in the tumors in the MPBX combination group increased by 2.0-fold compared to the level in the IDA-alone group. On the other hand, as regards IDA-induced bone marrow suppression, the combination of MPBX with IDA reduced the decrease in the bone marrow cell number by 30% compared to that in the IDA-alone group. In addition, the IDA concentration in the bone marrow cells was decreased by the combination of MPBX with IDA. An in vitro experiment showed that MPBX facilitated IDA influx and suppressed IDA efflux in P388 cells. In conclusion, the combination of MPBX with IDA increased the antitumor activity and decreased the bone marrow suppression. Therefore, we expect that the combination of MPBX with IDA will be useful for leukemia chemotherapy.     

Long-term survival after induction therapy with idarubicin and cytosine arabinoside for de novo acute myeloid leukemia

 We treated 153 patients with de novo acute myeloid leukemia (AML) with two induction courses of conventional-dose cytosine arabinoside (ara-C) and idarubicin (AIDA) followed by either a third course of AIDA, high-dose ara-C or bone-marrow transplantation. The complete remission (CR) rate for all patients was 63.4%, with a higher CR rate for patients with a normal (versus unfavorable) karyotype (73.2% vs 52.5%;P=0.038). The probability of overall survival (OS) was 30.7% after 5 years (26.3% after 7 years). Improved OS at 5 years could be observed for patients up to 50 years old versus patients older than 50 years of age (37.6% vs 19.9%;P=0.001) and patients with a normal (versus unfavorable) karyotype (42.9% vs 14.1%;P=0.0016). Disease-free survival (DFS) after 5 years was 33.2% for all 97 CR patients and was significantly better for patients with a normal (versus unfavorable) karyotype (44.3% vs 12.3%;P=0.003). Multivariate analysis revealed that the age for OS (P<0.02) and the karyotype for both OS (P<0.03) and DFS (P<0.05) were independent prognostic factors. In conclusion, AIDA is an effective and well-tolerated induction regimen (even in elderly patients) with a 5-year survival of more than 30% when combined with ara-C-containing postremission therapy. The karyotype is the most powerful prognostic factor for predicting the outcome of patients treated with this protocol. Received: 10 December 1999 / Accepted: 25 February 2000     

Idarubicin and intermediate-dose cytarabine for myeloid blast crisis of chronic myelogenous leukemia – results of a phase-II trial

 Sixteen patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in myeloid blast crisis were treated with cytarabine (AraC) 600 mg/m² two times daily for 5 days and idarubicin 12 mg/m² for 3 days. Patients achieving a second chronic phase received interferon (IFN) alpha 2b 5 mio units/day daily and AraC 20 mg/day subcutaneously 14 days every month. Study end points were remission rate and survival. Four patients (25%) entered a second chronic phase and had a median survival of 31.1 weeks (range 16.1–111 weeks). Nine patients (56%) experienced blast crisis again and had a median survival of 12.9 weeks (range 5.1–59.3 weeks). Three patients (18.8%) died of septic complications during marrow aplasia. The median overall survival was 16.1 weeks (range 2.6–111 weeks) with no significant difference between responders and nonresponding patients. We conclude that AraC/idarubicin is as effective as other intensive regimens in inducing second chronic phase in patients with myeloid blast crisis of CML. Remission duration and survival are comparable to previous results. Further studies to improve survival are required. Received: May 7, 1998 / Accepted: August 7, 1998