Preliminary Experience with a New Chemotherapy Regimen for Adults with Acute Lymphoblastic Leukemia

We treated 11 consecutive adult patients who presented with acute lymphoblastic leukemia to the University of Chicago with a novel, intensified chemotherapy regimen to evaluate the feasibility and toxicity of this program. Following a 5-drug induction therapy (course A), patients received sequential courses (B and C) of high-dose antimetabolite therapies, in part to replace cranial irradiation for CNS prophylaxis. All patients achieved a complete remission. The regimen was designed with a goal of administering all post-remission therapy in the outpatient setting. With the exception of the initial induction course (A), 31/38 total patient courses were administered in the outpatient clinic. As expected, the induction and consolidation courses (A and B) of this regimen were associated with grade 4 hematologic toxicity and significant but manageable infectious toxicity. Another novel aspect of the regimen included a combined intravenous and oral dosing schedule designed to sustain methotrexate levels × 1.0 μM^-for 30 hours (course C). There was minimal toxicity with the CNS prophylaxis/high-dose methotrexate course (C). Methotrexate levels at 30 hours ranged from 0.31-4.0 μM, with a median of 1.0 μM (n=37). This study demonstrates that this novel post-remission regimen is feasible in adults and that high concentrations of methotrexate can be sustained in the outpatient setting. The Cancer and Leukemia Group B is presently evaluating the efficacy of this regimen in a large phase II trial (CALGB study 19802).     

Standard vs Adapted Sunitinib Regimen in Elderly Patients With Metastatic Renal Cell Cancer: Results From a Large Retrospective Analysis

BackgroundThere are no data on the patterns of care and outcome of elderly patients with mRCC treated with sunitinib. In a retrospective study, we assessed the routine use of first-line sunitinib in mRCC patients aged ≥ 70 years.Patients and MethodsWe reviewed the clinical files of 185 patients aged ≥ 70 years with mRCC treated with first-line sunitinib in 17 Italian oncology units from February 2006 to September 2011. One hundred twenty-three patients (66.5%) received a standard 50 mg/d for a 4 weeks on/2 weeks off regimen (SR), and 62 patients (33.5%) received an AR consisting of 37.5 mg/d for a 4 weeks on/2 weeks off in 67.7% of cases.ResultsMedian age was 74 years. Patients treated with an AR were older than those treated with the SR (P < .0001). In the overall population, the median progression-free survival (PFS) was 11 months, and the median overall survival (OS) was 25.5 months. Grade 3-4 toxicities occurred in 87 of 123 SR (70.7%) and 32 of 62 AR (51.6%), respectively; dose reductions were required in 82 SR (66.7%) and 26 AR (41.9%), respectively; discontinuations because of therapy-related adverse events occurred in 25 SR (20.3%) and 15 AR (24.2%), respectively. In multivariate analysis, only performance status and the Heng score were predictors of either PFS or OS.ConclusionSunitinib is active and feasible in elderly patients with mRCC. A sunitinib AR could be considered as an option in selected older mRCC patients. The optimal treatment of frail patients with mRCC remains to be established.     

增强BEACOPP方案治疗晚期霍奇金淋巴瘤患者的远期疗效及安全性

1文献来源 Engert A, Diehl V, Escalated-dose BEACOPP patients with advanced-stage Franklin J, et al. in the treatment of Hodgkin＇ s lymphoma ：10 years of follow-up of the GHSG HD9 study [J]. J Clin Oncol, 2009, 27（27） ： 4548-4554.     

The efficacy and safety of bevacizumab combined with FOLFOX regimen in the treatment of advanced colorectal cancer: A systematic review and meta-analysis

Background:It is necessary to systematically evaluate the clinical efficacy and safety of bevacizumab (BEV) combined with 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX) regimen in the treatment of advanced colorectal cancer.Methods:We searched the PubMed et al databases for randomized controlled trials (RCTs) on the BEV combined with the FOLFOX regimen in the treatment of advanced colorectal cancer up to January 20, 2021. The Cochrane Collaborations’ risk of bias tool was used for the quality assessment of included RCTs. Revman5.3 software was used for meta-analysis.Results:Eleven RCTs with a total of 3178 patients with advanced colorectal cancer were included, meta-analysis results showed that the objective response rate (odds ratio [OR] = 3.15, 95% confidence intervals [CI]: 2.25–4.40, P < .001) and cancer control rate (OR = 2.73, 95% CI: 1.91–3.90, P < .001) of BEV + FOLFOX were higher than that of FOLFOX group. And the incidence of gastrointestinal adverse reactions (OR = 1.29, 95% CI: 1.07–1.55, P = .008) in the BEV + FOLFOX group was higher than that of the FOLFOX group, there were no significant differences in the incidence of leukopenia (OR = 1.04, 95% CI: 0.72–1.50, P = .83), hypertension (OR = 3.92, 95% CI: 0.81–18.88, P = .09) and neurotoxicity (OR = 1.00, 95% CI: 0.8–1.27, P = .98) between the 2 groups.Conclusion:BEV combined with the FOLFOX regimen is more effective than the FOLFOX regimen alone in the treatment of advanced colorectal cancer, but it may also increase the risk of gastrointestinal adverse reactions.     

Gestational diabetes mellitus shares polymorphisms of genes associated with insulin resistance and type 2 diabetes in the Greek population

Gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) share common pathophysiological features, including β-cell dysfunction and insulin resistance. In this study, we investigated the association between GDM and five recently identified T2D susceptibility loci, in a Greek population. We studied 148 women with GDM and 107 non-diabetic unrelated pregnant Greek women, for polymorphisms in the TCF7L2 gene (rs7903146 C/T), the PPARG gene (Pro12Ala), the KCNJ11 gene (E23K), the IRS1 gene (G972R) and in the FOXC2 gene (-512C>T). The T-allele of the TCF7L2 rs7903146 (C/T) polymorphism was found to be significantly associated with an increased risk of GDM [p?=?0.0003; odds ratio (OR) 2.04 (95%CI 1.38–3.00)]. Additionally, CT and TT genotypes were significantly overrepresented in women with GDM compared to controls (p?=?0.0003 and p?=?0.0148, respectively). Analysis of the IRS1 G972R polymorphism showed that the R-allele frequency was increased in women with GDM [(p?=?0.009; OR 1.67 (95%CI 1.14–2.47)]. The genotypes and allele frequencies of the other polymorphisms studied did not statistically differ between the GDM and the control women. Thus, our data suggest that the common T2D susceptibility polymorphism of TCF7L2 (rs7903146 C/T) gene, and the G972R polymorphism of the IRS1 gene, seem to predispose to GDM in Greek women.     

Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects

Aim:

To characterize the pharmacokinetics (PKs), pharmacodynamics (PDs), and tolerability of different dose regimens of prasugrel in healthy Chinese subjects.

Methods:

This was a single-centered, open-label, parallel-design study. Subjects received a single loading dose (LD) of prasugrel followed by once-daily maintenance dose (MD) for 10 d. They were enrolled into 3 groups: 60 mg LD/10 mg MD; 30 mg LD/7.5 mg MD; 30 mg LD/5 mg MD. Blood samples were collected after the first and last dose. The serum concentration of the active metabolite of prasugrel was determined using a LC/MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y₁₂ assay.

Results:

Thirty-six healthy native Chinese subjects (19 males) aged 18–45 were enrolled; mean age and body weight were similar across the treatment groups (n=12 for each). The metabolite AUC_0–4 and C_max increased dose-proportionally across the dose range of 5 mg to 60 mg. The median T_max was 0.5 h in all groups. The PD parameters, indicated by the inhibition of ADP-induced platelet aggregation, were met more rapidly in the 60 mg group than the 30 mg group after the LD (94%–98%). This high degree of inhibition of platelet aggregation was maintained following the 10 mg MD (87%–90%) and was lower in the 7.5 mg and 5 mg MD groups (79%–83% and 64%–67%, respectively). Prasugrel was well tolerated in healthy Chinese subjects for single doses up to 60 mg and a MD of 10 mg for 10 d.

Conclusion:

The PKs and PDs of the active metabolite of prasugrel were similar to those in Chinese subjects reported by a previous bridging study, which demonstrated that the exposure to the active metabolite in Chinese subjects was higher than in Caucasians.     

焦虑性与非焦虑性抑郁临床特征及疗效对照研究

目的 探讨焦虑性与非焦虑性抑郁患者的临床特征及疗效,为临床识别和有效治疗焦虑性抑郁提供依据.方法 对195例在我院住院的抑郁症患者,采用汉密顿抑郁量表(焦虑/躯体化因子分≥7分定义为焦虑性抑郁)筛选出焦虑性抑郁患者,统计焦虑性与非焦虑性抑郁患者的人口学资料及其临床特征;采用"两步"治疗法对两组患者进行药物治疗,观察12周.于治疗3周、6周、9周、12周末采用汉密顿抑郁量表、副反应量表评估临床疗效及不良反应.结果 195例抑郁症患者中,焦虑性抑郁92例,发生率为47.18%.与非焦虑组患者相比,焦虑性抑郁患者文化程度较低、无职业者多、年龄偏大、总病期较长、本次抑郁发作时间较长、抑郁发作次数较多、抑郁症状更严重、药物治疗痊愈率较低、达痊愈的治疗时间较长,差异均有显著或极显著性(P＜0.05或0.01).结论 焦虑性抑郁在抑郁症中常见,常规治疗方案疗效不理想,在临床治疗过程中需要对其焦虑性抑郁状况进行评估,制定有针对性的治疗方案,以提高临床疗效、有效地防止疾病的慢性化. 顿抑郁量表、副反应量表评估临床疗效及不良反应.结果 195例抑郁症患者中,焦虑性抑郁92例,发生率为47.18%.与非焦虑组患者相比,焦虑性抑郁患者 化程度较低、无职业者多、年龄偏大、总病期较长、本次抑郁发作时间较长、抑郁发作次数较多、抑郁症状更严重、药物治疗痊愈率较低、达痊愈的治疗时间较长,差异均有显著或极显著性(P＜0.05或0.01).结论焦虑性抑郁在抑郁症中常见,常规治疗方案疗效不理想,在临床治疗过程中需要对其焦虑性抑郁状况进行评估,制定有针对性的治疗方案,以提高临床疗效、有效地防止疾病的慢性化. 顿抑郁量表、副反应量表评估临床疗效及不良反应.结果 195例抑郁症患者中,焦虑性抑郁92例,发生率为47.18%.与非焦虑组患者相比,焦虑性抑郁患者 化程度较低、无职业者多、年龄偏大、总病期较长、本次抑郁发作时间较长、抑郁发作次数较多、抑郁     

血管内皮抑制素联合NP方案治疗晚期复发、转移性乳腺癌的疗效观察

目的观察血管内皮抑制素(恩度)联合NP方案治疗晚期复发、转移性乳腺癌的近期疗效及毒副作用。方法经病理证实的晚期复发、转移性乳腺癌患者15例,既往均接受多程化疗及内分泌治疗,现接受恩度联合NP方案化疗。化疗1周期后评价毒副反应,化疗2周期后评价化疗效果。结果 13例可评价疗效的病例中获得完全缓解(CR)1例、部分缓解(PR)3例、稳定(SD)7例和疾病进展(PD)2例,客观有效率30.1%,疾病控制率84.6%。全组患者无严重不良反应。结论在晚期乳腺癌患者中,一线治疗失败后改用恩度联合NP方案化疗后能改善患者生活质量,延长生存期,安全性好毒副反应低,值得临床进一步深入观察。     

Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13): clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols

The translocation t(1;19)(q23;p13)/der(19)t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19)t(1;19)-positive BCP ALL treated on two successive Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1·8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional chromosome abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7 years, the median white blood cell (WBC) count was 16 × 10(9)/l, and the female/male ratio was 1·2. The predicted event-free survival (EFS) at 5 and 10 years was 0·79, whereas the predicted overall survival (OS) at 5 and 10 years was 0·85 and 0·82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS. Compared to cases with t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse in patients with t(1;19)/der(19)t(1;19) (P = 0·004).     

吉非替尼与多西他赛单药治疗老年晚期肺腺癌的疗效及对心肌损伤的初步分析

目的 回顾性分析吉非替尼和多西他赛单药治疗老年晚期非小细胞肺癌的临床疗效及治疗过程中对患者心肌酶肌酸激酶同工酶(CK-MB)和射血分数的影响;比较两组对患者心肌损伤的差异.方法 2008年1月至2009年12月就诊我院的老年(年龄＞65岁)确诊晚期肺腺癌患者32例.多西他赛组(n=18):多西他赛65 mg/m2,第1天,21天1个周期,连续3个周期;吉非替尼组(n=14):吉非替尼250 mg/d,早餐后2小时口服,连续服用3个月.记录患者临床疗效、心肌酶CK-MB和射血分数变化.结果 吉非替尼组:完全缓解(CR)1例,部分缓解(PR)3例,稳定(SD)3例,疾病进展(PD)7例;多西他赛组:完全缓解(CR)0例,部分缓解(PR)4例,稳定(SD)6例,疾病进展(PD)8例,吉非替尼组与多西他赛组临床有效率分别为28.6%和22.2%,两组比较差异无统计学意义(P＞0.05);吉非替尼组治疗前后心肌酶肌酸激酶CK-MB均值(17.72±9.12)U/L vs(24.03±7.01) U/L,治疗前后比较差异有统计学意义(P＜0.05),多西他赛组治疗前后心肌酶肌酸激酶CK-MB均值(16.62±10.21)U/L vs(29.94±8.03)U/L,治疗前后比较差异亦有统计学意义(P＜0.05);吉非替尼和多西他赛组间治疗前比较差异无统计学意义(P＞0.05),但治疗后两组比较差异有统计学意义(P＜0.05).射血分数变化:吉非替尼组治疗前后射血分数均值(59.43±8.75)%vs(59.01±7.67)%;多西他赛组治疗前后射血分数均值(60.21±8.97)%vs(59.31±9.21)%,射血分数在治疗前后并未出现明显变化(P＞0.05).结论 吉非替尼与多西他赛在治疗老年晚期肺腺癌有一定疗效;吉非替尼和多西他赛均对心肌一定的损伤;单药化疗将成为老年晚期肺腺癌有效的治疗手段之一.