Therapy-related myeloid leukemia following platinum-based chemotherapy for ovarian cancer

A 40-year-old woman, who had suffered from AML (M1) in 1983, developed ovarian cancer (stage IIIc) in December 1996 after long-term remission. She underwent surgical resection of the cancer, 10 courses of standard chemotherapy and tandem PBSCT (total dose: CBDCA 6,750 mg, CDDP 200 mg, CPA 16,000 mg, THP-ADR 450 mg). After receiving the last course of chemotherapy in June 1998, she was referred to our hospital in September 1998 because of pancytopenia. Laboratory findings showed pancytopenia with 34% leukemic cells, which were positive for alpha NBE and negative for POX and CAE. Surface-marker analysis of the leukemic cells showed positivity for CD11c, CD33, CD56, and DR, and chromosome analysis revealed 47, XX, +8. The patient was diagnosed as having AML (M5a), and received induction therapy consisting of IDR and Ara-C, which led to complete remission. As she had not received etoposide, this case was thought to have been therapy-related leukemia due to the platinum agents used for treating the ovarian cancer.     

ERCC1 as a risk stratifier in platinum-based chemotherapy for nonsmall-cell lung cancer

PURPOSE OF REVIEW: Cisplatin-based chemotherapy remains the treatment of choice in advanced nonsmall-cell lung cancer. The development of predictive biomarkers able to identify lung-cancer patients who are most likely to benefit from cisplatin-based chemotherapy would be a powerful tool. Many reports have explored the role of ERCC1 expression in the repair mechanism of cisplatin-induced DNA adducts in cancer cells. RECENT FINDINGS: Using immunohistochemistry in resected tumors, the International Adjuvant Lung Cancer Trial showed that high ERCC1 protein expression was associated with improved survival in patients who did not receive chemotherapy. In contrast, the benefit of adjuvant cisplatin-based chemotherapy was more profound in patients with low ERCC1 expression. Other investigators studying mRNA expression in tumor biopsies from patients treated with cisplatin and gemcitabine showed that patients with low ERCC1 mRNA expression have a longer median survival compared to those with high expression. SUMMARY: High ERCC1 expression is predictive of resistance to platinum-based therapy. Thus, there is solid evidence to support ERCC1 as a useful marker of clinical resistance to platinum-based chemotherapy in the adjuvant setting of nonsmall-cell lung cancer. Meanwhile, optimization of methodology and standardization of technical procedures seem necessary before larger prospective studies can address the same question.     

Treatment of recurrent ovarian cancer relapsing 6-12 months post platinum-based chemotherapy

Platinum-containing regimens are the mainstay of initial treatment for ovarian cancer and for platinum-sensitive recurrent disease. In recurrent ovarian cancer, the effectiveness of platinum retreatment is dependent on the relapse-free and treatment-free intervals. Platinum agents can be effectively re-administered to patients with disease that relapses >12 months after completion of a platinum regimen. Ovarian cancer that relapses 6-12 months after treatment with a platinum regimen is considered partially platinum sensitive. Phase III studies of combination regimens versus platinum monotherapy and comparing various non-platinum agents administered as monotherapy generally do not report separate data for partially platinum-sensitive patients. Studies reporting data in patients with a platinum-free interval > or =6 months demonstrate advantages for pegylated liposomal doxorubicin (PLD) versus paclitaxel and PLD versus topotecan. A platinum-taxane combination or single-agent PLD is recommended for the treatment of partially platinum-sensitive disease by the UK National Institute for Health and Clinical Excellence.     

以铂类为基础的两药联合方案治疗老年晚期非小细胞肺癌临床研究

目的 评价老年晚期非小细胞肺癌(NSCLC)患者接受以铂类为基础的两药联合化疗的疗效和安全性. 方法 对我院41例年龄≥70岁的老年晚期NSCLC患者应用以铂类为基础的两药联合方案化疗的情况进行了回顾性分析. 结果 41例患者中采用长春瑞滨方案的18例(43.9%),吉西他滨方案的9例(22.0%)、紫杉醇和多西紫杉醇方案各7例(17.1%).全组总有效率为19.5%,中位疾病进展时间和中位生存期分别为5.8个月和14.2个月,1年生存率为65.8%.化疗的主要不良反应为骨髓抑制,主要以白细胞和血小板减低为主,给予对症处理后可以恢复.患者无化疗相关死亡发生,有3例患者因出现Ⅲ～Ⅳ度骨髓抑制仪化疗1个周期. 结论 以铂类为基础的联合化疗方案治疗一般状况较好的老年晚期NSCLC疗效确切且耐受性较好.     

Utility of subsequent conventional dose chemotherapy in relapsed/refractory transplant-eligible patients with diffuse large B-cell lymphoma failing platinum-based salvage chemotherapy

Abstract

Up to 60% of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) do not respond to second-line (salvage) chemotherapy and hence are not offered autologous hematopoietic cell transplantion (AHCT). The utility of further salvage chemotherapy in an attempt to proceed with AHCT remains undefined. The authors reviewed 201 patients with DLBCL relapsed/refractory to anthracycline-based chemotherapy who received first-line salvage chemotherapy containing cis-platinum. Of the 120 non-responders to first-line platinum-based salvage chemotherapy, 73 received second-line salvage chemotherapy. The response rate to second-line salvage chemotherapy was 14%. Factors predicting lack of response were progression on primary therapy (p = 0·007), abnormal lactate dehydrogenase findings (p = 0·0027) and tumor bulk (p = 0·013) at second progression. Eight patients who responded received AHCT and appeared to have comparable survival to those transplanted after one salvage regimen. The authors conclude that the utility of second-line salvage chemotherapy is low, and that it is best reserved for patients demonstrating initial anthracycline sensitivity and low tumor burden.     

Utility of subsequent conventional dose chemotherapy in relapsed/refractory transplant-eligible patients with diffuse large B-cell lymphoma failing platinum-based salvage chemotherapy

Up to 60% of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) do not respond to second-line (salvage) chemotherapy and hence are not offered autologous hematopoietic cell transplantation (AHCT). The utility of further salvage chemotherapy in an attempt to proceed with AHCT remains undefined. The authors reviewed 201 patients with DLBCL relapsed/refractory to anthracycline-based chemotherapy who received first-line salvage chemotherapy containing cis-platinum. Of the 120 non-responders to first-line platinum-based salvage chemotherapy, 73 received second-line salvage chemotherapy. The response rate to second-line salvage chemotherapy was 14%. Factors predicting lack of response were progression on primary therapy (p = 0.007), abnormal lactate dehydrogenase findings (p = 0.0027) and tumor bulk (p = 0.013) at second progression. Eight patients who responded received AHCT and appeared to have comparable survival to those transplanted after one salvage regimen. The authors conclude that the utility of second-line salvage chemotherapy is low, and that it is best reserved for patients demonstrating initial anthracycline sensitivity and low tumor burden.     

NSCLC患者血清miR-181a的表达变化及其与铂类药物化疗敏感性的关系

目的观察微小RNA（miR）-181a在早期非小细胞肺癌（NSCLC）患者血清中的表达变化,并分析其与铂类药物化疗效果的相关性。方法采用茎环结构的逆转录实时定量PCR方法,检测40例早期NSCLC患者（NSCLC组）术前及其中30例铂类药物化疗前后血清miR-181a水平,同时设40例健康体检者为对照组;分析血清miR-181a水平与NSCLC临床病理特征及铂类药物化疗效果的关系。结果NSCLC组术前和对照组血清miR-181a表达量分别为0．00259、0．00729（P〈0．0001）,前者与肿瘤临床病理特征问无统计学相关性（P均〉0．05）;NSCLC组30例患者化疗前后血清miR-181a相对表达量分别为0．00279、0．00625（P=0．0001）,其中化疗无效、有效者分别为0．00456、0．00793,化疗无效者显著低于化疗有效者及对照组（P分别为0．015、0．005）,后两者比较无显著差异（P=0．806）。结论miR-181a在早期NSCLC患者血清中的水平降低,并与铂类药物化疗敏感性相关;可能作为潜在的生物标记物用于NSCLC的早期诊断及化疗敏感性预测。     

肺癌铂类药物化疗敏感性与基因多态性的研究进展

铂类药物是非小细胞肺癌最常用的化疗药物。研究表明不同个体间对铂类药物化疗敏感性有显著性差异,这可能与个体遗传基因的多态性有关。因此,探讨非小细胞肺癌患者铂类药物化疗敏感性与基因多态性关系的研究对于临床个体化疗方案的制定具有重要的意义。     

NSCLC患者XPG、MDR-1基因单核苷酸多态性与铂类药物化疗疗效的关系

目的探讨晚期非小细胞肺癌（NSCLC）患者XPG、MDR-1基因单核苷酸多态性与铂类药物短期化疗疗效的关系。方法对61例晚期NSCLC患者，采用顺铂（DDP）为主的化疗方案治疗，2～3个周期后进行临床疗效评价。以PCR—RLFP方法进行XPGC3507G、MDR-1C3435T、MDR-1G2677A／T的基因型分析，比较不同基因型患者的化疗效果。结果MDR1C3435T型为C／C者的化疗有效率为59．3％，显著高于至少含有一个T等位基因者的26．5％（OR=0．442，95％CI=0．133～1．467，P〈0．05）；MDR-1G2677A／T位点至少一个T等位基因者的化疗有效率13．0%，要显著低于其他基因型者的57．9％（OR=0．384，95％CI=0．187～0．789，P〈0．01）；XPGC3057位点各基因型化疗有效率差异无统计学意义。结论MDR-1C3435T、MDR-1G2677A／T位点多态性可降低铂类药物治疗治疗NSCLC的疗效。XPGC3507G位点多态性对铂类药物治疗NSCLS疗效无影响。     

Platinum-DNA adducts in leukocyte DNA correlate with disease response in ovarian cancer patients receiving platinum-based chemotherapy.

Fifty-five ovarian cancer patients receiving platinum drug-based chemotherapy have been studied prospectively to determine the extent of formation of the bidentate intrastrand adducts of diammineplatinum covalently attached to the N7 positions of adenosine and/or guanosine in leukocyte DNA. Data for clinical response, obtained from medical records, were then correlated with the adduct values. Patients were treated with platinum-based single-agent or combination chemotherapy containing cis-diamminedichloroplatinum (II) or diamminecyclobutane-dicarboxylatoplatinum on approved experimental protocols. Adduct measurements were performed by ELISA, and disease response to therapy was assessed by standard oncologic criteria. This study comprises a total of 101 blood samples obtained after intravenous cis-diamminedichloroplatinum (II) or diamminecyclobutane-dicarboxylatoplatinum infusion from 55 individuals, and in each case the highest (or "peak") adduct level for each patient was chosen for statistical analysis. Values for median adduct levels in patients grouped by complete response, partial response, and no response were 212, 193, and 62 amol of adduct per microgram of DNA, respectively. Analysis of these data by Jonckheere's test (an extension of the Mann-Whitney test) shows that higher levels of adduct formation correlates with disease response with a two-sided P value of 0.030. Of eight patients on single-agent therapy whose buffy-coat samples did not have measurable adduct levels, none responded to therapy. Analysis of these data using the exact test for trend shows that the formation of adduct at a level of 160 amol/micrograms of DNA or greater correlates with disease response with a two-sided P value of 0.032. Thus in ovarian cancer patients, the formation of the intrastrand diammineplatinum adducts in leukocyte DNA is associated with favorable disease response to cis-diamminedichloroplatinum (II) or diamminecyclobutane-dicarboxylatoplatinum chemotherapy.     

结直肠癌组织乳腺癌易感基因1的表达及与铂类化学治疗疗效的关系

目的 探讨乳腺癌易感基因1(BRCA1)在人结直肠癌中的表达及其与铂类化学治疗疗效的相关性.方法 选取术后接受奥沙利铂化学治疗的78例结直肠癌患者,取其手术标本,另取正常结肠黏膜标本14份、结直肠癌标本中非癌组织部分标本12份.采用免疫组织化学法检测各组织中BRCA1的表达情况并行x2检验.随访结直肠癌患者的生存情况,用Kaplan-Meier生存曲线进行生存分析的比较,并行Log-rank检验.结果 结直肠癌组织中BRCA1的阳性率[52.6％ (41/78)]低于癌旁组织(11/12,x2=6.518,P=0.011)和正常结肠黏膜组织(13/14,x2=7.949,P=0.005).结直肠癌组织分化越差,BRCA1阳性率越低(x2=14.160,P=0.001).BRCA1阴性的结直肠癌患者中位无病生存期为51.0个月(95％CI:47.7～54.4个月),长于BRCA1阳性者[45.0个月(95％CI:36.6～53.4个月),x2=4.367,P=0.032].结论 BRCA1阴性的结直肠癌患者接受奥沙利铂为主的化学治疗可获生存获益.BRCA1表达情况或可作为结直肠癌患者术后化学治疗方案选择及预后判断的指标.     

Experience with platinum-based and high-dose chemotherapy in patients with gestational trophoblastic disease: possible implications for future management

Purpose Despite the similarities between the chemotherapeutic management of advanced gestational trophoblastic disease (GTD) and ovarian germ cell tumors, important differences exist between the malignancies, particularly in the use of cisplatin.Methods Three patients with persistent or recurrent GTD cared for at the Cleveland Clinic received a high-dose chemotherapy program (with stem cell support), one as management for etoposide-associated acute leukemia resulting from her standard dose treatment program.Results While the indications for use of a dose-intensive strategy, and the ultimate clinical course, differed in the three patients, collectively these cases raise relevant questions regarding optimal management of high risk and recurrent GTD.Conclusion The experience represented in this report support the earlier use of cisplatin-based chemotherapy in the management of high-risk and recurrent GTD, and the possible administration of a high-dose chemotherapy program in the rare patient who recurs following standard dose platinum-based treatment.     

A randomized trial of different docetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy

STUDY OBJECTIVE: Docetaxel has shown activity in the second-line treatment of non-small cell lung cancer (NSCLC). Phase II studies have suggested that weekly therapy with docetaxel probably has a better toxicity profile than the conventional schedule of once every 3 weeks. Our aim was to evaluate and compare the efficacy of different docetaxel schedules in NSCLC patients who did not respond to previous platinum-based chemotherapy. SETTING: National teaching hospital in Taiwan. METHODS: Treatment consisted of the following: (1) docetaxel, 35 mg/m(2) IV infusion (D(35)) on days 1, 8, and 15 every 4 weeks; (2) docetaxel, 40 mg/m(2) IV (D(40)) on days 1 and 8 every 3 weeks; and (3) docetaxel, 75 mg/m(2) IV (D(75)) on day 1 every 3 weeks. Patients were randomized at a ratio of 2:2:1, with the D(75) arm as the control arm. From 2002 to 2004, 161 patients were enrolled into the study. RESULTS: The number of patients enrolled in each arm of the study was as follows: D(35) group, 64 patients; D(40) group, 64 patients; D(75) group, 33 patients. The mean ages of patients were as follows: D(35) group, 65 years of age; D(40) group, 63 years of age; D(75) group, 64 years of age. The median number of cycles of chemotherapy received in each group was as follows: D(35) group, 4; D(40) group, 3; D(75) group, 4. The objective response rates were as follows: D(35) group, 17.2%; D(40) group, 10.9%; D(75) group, 6.1% (p = 0.615). The major toxicity was myelosuppression. Grades 3/4 leukopenia and neutropenia were significantly higher in the D(75) arm of the study (p < 0.001). Drug-induced pneumonitis occurred more frequently in patients on a weekly schedule than in those on a schedule of every 3-weeks (p = 0.05). The median survival times were as follows: D(35) group, 8.4 months; D(40) group, 7.2 months; and D(75) group, 9.5 months (p = 0.855). The 1-year survival rates were 32.8%, 31.9%, and 28.7%, respectively. Lung cancer symptom scores showed no obvious differences among the different treatment arms, except for some minor items. CONCLUSIONS: Weekly docetaxel chemotherapy produces less myelosuppression, and better compliance and response rates than the conventional chemotherapy administered every 3 weeks. These effects were more evident in the D(35) group weekly schedule than in the D(40) weekly schedule. However, physicians should pay more attention to the possibility of a higher frequency of docetaxel-induced pneumonitis in patients receiving treatment on the weekly schedule of treatment.     

晚期非小细胞肺癌ERCC1 XRCC1基因多态性与铂类化疗疗效研究

以铂类为基础的两药化疗是晚期非小细胞肺癌(NSCLC)的主要治疗手段,有效率约为30%。然而不同个体对化疗疗效和耐受性的差异巨大。机体的损伤修复系统可以修复铂类药物引起的DNA损伤,影响化疗疗效,DNA修复基因的单核苷酸构象多态性(SNP)是导致这种差异的重要原因和分子基础,ERCC1和XRCC1分别在核苷酸切     

XRCC1和XPD单核苷酸多态性与非小细胞肺癌铂类药物化疗敏感性的关系

目的研究X线修复交叉互补基因1（XRCC1）和着色性干皮病基因（XPD）单核苷酸多态性与老年晚期非小细胞肺癌（NSCLC）铂类药物化疗敏感性关系。方法应用聚合酶链反应结舍限制性片段长度多态性（PCR-RFLP）的方法检测81例以铂类药物为主要化疗方案的NSCLC患者XRCC1 Arg399Gln和XPD Lys751Gin基因型多态性，采用非条件Logistic回归分析不同基因型与化疗疗效的关系。结果81例患者化疗总有效率为35．8％，其中完全缓解（CR）、部分缓解（PR）、稳定（SD）和进展（PD）患者分别为0、29、31、21例。携带至少1个XRCC1 399Arg等位基因的患者化疗敏感性是携带Gln／Gln基因型患者的4.52倍（OR=4．52，95％CI=1.11—18．38）。未发现XPD Lys751Gin遗传多态与化疗敏感性相关。结论XRCC1 Arg399Gln多态可能与晚期NSCLC铂类药物化疗敏感性有关。     

Tumor-marker analysis and verification of prognostic models in patients with cancer of unknown primary, receiving platinum-based combination chemotherapy

Objectives To evaluate the usefulness of tumor-marker measurements and to identify prognostic factors in patients with cancer of unknown primary (CUP), receiving platinum-based combination chemotherapy and to verify the adjustment of previously reported prognostic models in this population.Methods We conducted univariate and multivariate analyses in consecutive patients with CUP receiving platinum-based combination chemotherapy. Previously reported prognostic models were then validated in this population.Results A total of 93 patients were analyzed and the response rate to platinum-based chemotherapeutic regimens among the 93 patients was 39.8%. The median time to progression and overall survival period were 4.1 and 12.4 months, respectively. The ST-439 level was significantly higher in patients with histologically confirmed adenocarcinoma than in patients with poorly differentiated adenocarcinoma or poorly differentiated carcinoma. A multivariate analysis indicated that performance status, the number of involved organs, and the serum lactate dehydrogenase level were the prognostic factors of the outcome. Both the previously reported prognostic models for predicting the duration of survival in this population were shown to be valid.Conclusion Tumor-marker measurements are not helpful in the management of patients with CUP. Previously reported prognostic models may be useful for selecting indication for chemotherapy or for stratifying the patients in clinical trial.     

培美曲塞联合铂类化疗治疗晚期非小细胞非鳞肺癌临床分析

目的 探讨培美曲塞联合铂类化疗治疗晚期非小细胞非鳞肺癌的效果.方法 选取2017年1月至2019年7月在蚌埠医学院第二附属医院治疗的晚期非小细胞非鳞肺癌患者70例,根据选取的铂类药物分为观察组36例和对照组34例,观察组给予培美曲塞联合顺铂,对照组给予培美曲塞联合卡铂,观察两组近期疗效、不良反应及总生存时间,检测化疗前...     

Traditional herbal medicine combined with first-line platinum-based chemotherapy for advanced non-small-cell lung cancer: A PRISMA-compliant systematic review and meta-analysis

Background:Non-small-cell lung cancer (NSCLC) is a major health burden in many countries. This review aimed to evaluate the efficacy of traditional herbal medicine (THM) combined with first-line platinum-based chemotherapy (PBCT) for the treatment of advanced NSCLC.Methods:From inception to April 2021, relevant studies were retrieved from 9 electronic databases. Randomized controlled trials (RCTs) comparing survival outcomes of THM + PBCT treatment with PBCT treatment in patients with advanced NSCLC were reviewed. The risk of bias was evaluated using the Cochrane Risk of Bias Tool. Overall survival, 1-year survival, progression-free survival or time to progression, tumor response rate, and adverse effects were analyzed.Results:Sixteen RCTs comprising 1445 patients were included. The meta-analysis indicated that THM + PBCT treatment, compared to PBCT alone, could improve overall survival (median survival ratio = 1.24, 95% confidence intervals [CI] [1.11, 1.39], P < .001), progression-free survival/time to progression (median survival ratio = 1.22, 95% CI [1.09, 1.37], P < .001), and the 1-year survival rate (risk ratio [RR] = 1.56, 95% CI [1.31, 1.86], P < .001). THM + PBCT also led to a higher tumor response rate (RR = 1.39, 95% CI [1.22, 1.59], P < .001) and lower incidence of thrombocytopenia (RR = 0.72, 95% CI [0.56, 0.92], P = .009) and nausea/vomiting (RR = 0.35, 95% CI [0.21, 0.57], P < .001), while there was no significant effect observed on leukopenia (RR = 0.68, 95% CI [0.34, 1.36], P = .27).Conclusion:THM, when used in combination with PBCT, might increase survival and the tumor response rate while decreasing the side effects caused by chemotherapy in patients with advanced NSCLC. However, considering the limited methodological qualities of the included trials, more rigorous RCTs are needed.     

Associated factors with constipation and health-related quality of life in lung cancer patients with platinum-based chemotherapy: A cross-sectional study

The main purpose of this study was to investigate current state of constipation for lung cancer (LC) patients receiving platinum-based chemotherapy. The relationships between social demography, clinical variables, psychological status, and constipation were analyzed. In addition, quality of life (QoL) in LC patients with constipation was also analyzed. One hundred LC patients participated in this cross-sectional study. Under the guidance of the researchers, Functional Living Index-Emesis, Piper Fatigue Scale, Patient Health Questionnaire, Generalized Anxiety Disorder-7, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0), Pittsburgh Sleep Quality Index, General Well-being Scale, Social Support Rate Scale, General Self-Efficacy Scale, and other related questionnaires were completed. The result showed the symptom of constipation was observed in 41 (41%) LC patients. The occurrence and development of constipation were associated with gender, food intake, exercise, nausea, fatigue, anxiety, depression, sleep disorders, and happiness. The study also found patients with constipation had significant lower QoL scores, especially the score in the general state. Constipation was very common in LC patients undergoing platinum-based chemotherapy. Reduced food intake and fatigue were the independent factors. Constipation significantly affects the QoL of the patients. Therefore, more attention should be paid to the risk factors of constipation in LC patients undergoing platinum-based chemotherapy, the earlier intervention was done to these patients, the better to improve their QoL.