MIEP方案治疗复发或难治非霍奇金淋巴瘤疗效报告

目的　观察MIEP化疗方案治疗复发或难治非霍奇金淋巴瘤 (NHL)临床疗效和毒副作用。方法　 3 5例复发或难治NHL患者给予米托蒽醌 (MIT) 10mg/m2 静滴 ,d1;异环磷酰胺 (IFO) 1 2g/m2 静滴 ,d1～ 4,美司那 (Mesna) 40 0mg用IFO后 0、4、8h静推 ;依托泊甙 (VP 16) 65mg/m2 静滴 ,d1～ 4;强的松 (PRED) 10 0mg口服 ,d1～ 5。 2 1～ 2 8天为一周期 ,至少 3个周期。结果　MIEP方案化疗的疗效CR 2 8 6% ,PR 3 7 1% ,总有效率 65 7%。中位生存期为 19个月。毒副作用主要为骨髓抑制 ,白细胞减少发生率为 10 0 % ,其中Ⅲ度、Ⅳ度发生率为 71 4%。结论　MIEP方案治疗复发或难治非霍奇金淋巴瘤有效率高 ,毒性反应可耐受。     

Treatment of Advanced Gastric Cancer with a Modified Regimen of Etoposide/Leucovorin/5-Fluorouracil

The efficacy and toxicity of a combination of etoposide 100 mg/m²/day iv on day 2-4, leucovorin 300 mg/m²/day iv, and 5-FU 500 mg/m² day iv on day 1-5 every 4 weeks were assessed in 21 patients with advanced gastric cancer with measurable or evaluable diseases. Eight patients had an objective response, including 3 in CR. The overall response rate was 38.1% (95% CI 33.4-42.8%). Five of 8 patients who exhibited locally advanced and unresectable diseases had an objective response (2 CR, 3 PR). The response rate in patients with metastatic disease was 23.0% (95% CI 14.4-31.6%). The median progression-free interval and overall survival time were 7 and 10 months, respectively. The most frequent side effect was alopecia (Gr I/II 71.4%). No treatment-related death occurred. Modified ELF is a relatively effective and tolerable combination regimen for advanced gastric cancer and can be safely administered to elderly patients and patients with systemic diseases.     

Phase II Study of Roniciclib in Combination with Cisplatin/Etoposide or Carboplatin/Etoposide as First-Line Therapy in Patients with Extensive-Disease Small Cell Lung Cancer

Introduction

This phase II study evaluated the efficacy and safety of the pan-cyclin–dependent kinase inhibitor roniciclib with platinum-based chemotherapy in patients with extensive-disease SCLC.

Etoposide in the treatment of elderly/poor-prognosis patients with small-cell lung cancer

Survival rates for cancer have improved in recent decades, specifically for younger patients. However for those over 65, who account for over half of all cancer patients, mortality rates remain poor. In those with small-cell lung cancer the achievement of cure is possible in only a minority (5–10%). For the elderly and those with extensive disease we have found that the use of oral etoposide offers similar survival rates to more intensive regimens, with minimal side effects and hospitalisation. Thus the expansion of the elderly population mandates for more specific chemotherapeutic approaches in this group.Paper presented at the Topoisomerase Inhibitors Conference, University of Maryland Cancer Center, 27–30 October 1993, Monterey, California, USA. Supported in part by Bristol Myers Oncology Division     

Etoposide protein binding in cancer patients

The protein binding of etoposide was studied in vivo in 36 cancer patients receiving etoposide therapy. Free etoposide was separated from plasma using an ultrafiltration method and the etoposide concentrations (free and total) were measured by high-performance liquid chromatography (HPLC). Considerable interpatient variation in the protein binding of etoposide was observed. The protein binding of etoposide varied from 80% to 97% (mean, 93%). Univariate analysis showed a significant inverse correlation between the free fraction of etoposide and serum albumin (r=–0.74), daily dose (r=–0.37) and age (r=–0.34). Multivariate analysis demonstrated that serum albumin and age were independent predictors of the etoposide free fraction. Serum bilirubin showed no correlation with etoposide protein binding. There is wide variation in etoposide protein binding in cancer patients, which is mostly dependent on serum albumin concentration.     

Etoposide and cisplatinum in resistant lymphomas

Summary Etoposide and cisplatinum have used separately to treat refractory lymphomas. This report describes 22 patients in whom these two agents were used in conjunction. All had been extensively treated with standard therapies previously. The combination of etoposide and cisplatinum was chosen on the basis of preclinical evidence for synergy and because these agents do not cross-react. Cisplatinum was continuously infused for 5 days at a dose of 15 mg/m²/d. As a push a 100 mg/m²/d dose of etoposide was injected on days 1 and 2 of treatment. This schedule produced good responses in 18 patients, i.e. 15 partial remissions and three complete remissions. The side effects were acceptable.     

Comparison of Amrubicin and Weekly Cisplatin/Etoposide/Irinotecan in Patients With Relapsed Small-cell Lung Cancer

Background

Although several agents have been introduced for the treatment of relapsed small-cell lung cancer (SCLC), there is still only limited evidence regarding second- and later-line chemotherapies for these patients.

Etoposide kinetics in patients with obstructive jaundice

The kinetics and urinary excretion of etoposide and etoposide glucuronide were determined in 11 patients with obstructive jaundice (bilirubin greater than 2.0 mg/dL) and in 23 patients with normal renal and hepatic function. Mean (+/- SE) measurements of clearance (24.5 +/- 2.06 v 26.5 +/- 2.05 mL/min/m2), half-life (5.7 +/- 0.5 v 6.4 +/- 0.5 hours), and volume of distribution (12.4 +/- 1.1 v 13.7 +/- 1.6 L/m2) were not significantly different in patients with jaundice when compared with controls. Similarly, etoposide kinetics in three patients determined during a period of hyperbilirubinemia were not different from measurements made in the same patients following resolution of their obstructive jaundice. In patients with jaundice, 46% of an administered etoposide dose was excreted in the urine as etoposide compared with 35% in controls (P = .15). Urinary excretion of etoposide glucuronide accounted for 29% of an administered etoposide dose in control patients and 15% in those with hepatic obstruction (P = .03). Biliary etoposide excretion measured in four patients with T-tubes was insignificant (less than 2.0% of an administered dose). The calculated renal clearance of etoposide was 11.5 mL/min/m2 in patients with jaundice and 10.4 mL/min/m2 in controls (P = .53). Respective metabolic clearance was 4.9 and 6.9 mL/min/m2 in these two study groups (P = .13). Although hepatic metabolism of etoposide may be slightly decreased in patients with obstructive jaundice, a modest increase in renal etoposide excretion appears to compensate for this change, so that total clearance is similar in the patients with jaundice when compared with controls. No etoposide dose reductions appear to be needed in treating patients with obstructive jaundice who have normal renal function.     

VP16-213 (Etoposide)

Conclusion VP16-213 is a new semisynthetic podophyllotoxin derivative, which appears to have a unique mode of action. Early suggestive data of activity in small cell lung cancer [21, 25] have ben confirmed and the single-agent response rate remains at over 40% with well more than 200 patients studied. It also shows a pronounced antitumor activity in the treatment of testicular cancer, monocytic or myelomonocytic leukemia, non-Hodgkin's lymphomas and hepatocellular carcinoma. Its role in some other neoplasms, like non-small cell lung cancer and breast cancer, has still to be ascertained.New data on its pharmacokinetic properties are being rapidly accumulated. Based on this knowledge a more optimal schedule of administration can be expected. New modes of administration, which like, e.g., continuous infusions in the past were only occasionally used [6, 36], are presently being thoroughly investigated. One might therefore reasonably hope, that in the next few years all potentialities of the drug will be more exactly defined.Retropectively the phase-I-II trials with VP16-213 might be viewed as an example of the methodological difficulties encountered in the clinical evaluation of new agents. Some pitfalls can probably be avoided by implementing a more stringent and standardized methodology. Other difficulties seem on the contrary to represent inherent drawbacks of our current approach. Hopefully the stem cell clonogenic assay will in future turn out to be a useful tool for the solution of some of these remaining problems [34].     

Etoposide and split-dose cisplatin in bronchogenic carcinoma

The Hoosier Oncology Group (HOG) treated 13 patients with bronchogenic carcinoma with an innovative schedule of cisplatin and VP-16. Unexpected toxicity was noted, with five deaths secondary to granulocytopenia and septic shock and three episodes of renal failure. Despite early closure of this study, we conclude that this schedule of cisplatin and VP-16 results in greater toxicity than comparable dosages in a more routine schedule.     

Efficacy and Safety of the Modified EPOCH Regimen (Etoposide,Vincristine, Doxorubicin,Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study

BackgroundWe retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen.Patients and MethodsPatients received up to 6 mEPOCH cycles. Etoposide (50 mg/m²/day), doxorubicin (10 mg/m²/day), and vincristine (0.4 mg/m²/day) were each given as a continuous 96-hour infusion on days 1 to 4. Prednisolone (40 mg/m²/day) was given intravenously or orally on days 1 to 4 and then tapered and stopped on day 7, and carboplatin (dose calculated for each patient individually using Calvert’s formula according to a target under the curve of 3 mg/mL/min) was given as a 2-hour intravenous infusion on day 6.ResultsIn 103 patients, overall response rate and complete response rate were 58% and 25%, respectively. With a median follow-up of 8.9 months, the median survival time was 9.8 months (95% confidence interval, 7.2-13.9 months). The median progression-free survival (PFS) was 4.2 months (95% confidence interval, 3.4-5.7 months). Patients who completed ≥ 4 cycles experienced significantly better overall survival and PFS compared with those who completed < 4 cycles. Twenty-eight patients underwent allogeneic hematopoietic stem cell transplantation after mEPOCH and demonstrated significantly prolonged overall survival and PFS compared with those who did not undergo transplantation.ConclusionThe mEPOCH regimen is effective with tolerable adverse effects and may be an alternative treatment option for adult T-cell leukemia/lymphoma.     

Etoposide sensitivity of radioresistant human glioma cell lines

Purpose: Malignant gliomas display aggressive local behavior and are not cured by existing therapy. Etoposide, a topoisomerase-II-inhibitor agent, is one of the most active and useful antineoplastic agents. However, etoposide is not usually used on these tumors. We undertook an in vitro study to prove that etoposide is a useful drug for malignant gliomas. Methods: Five human glioma cell lines were the basis for this study. Following exposure to various concentrations of etoposide, the glioma cell lines were found to be sensitive; the median concentration inhibiting the number of cells by 50% (IC₅₀) was 8.76 μg/ml (range 8–15.8 μg/ml). Since topoisomerase II is the critical target for etoposide, it was of interest to determine the topoisomerase II activity (decatenation of kinetoplast DNA isolated from Cryphtidia fasciculata) and the etoposide-induced inhibition of topoisomerase II activity. Results: The topoisomerase II activity was homogeneous in glioma cell lines (average of 50% decatenation with 7,000 cells), and topoisomerase II was the target of the etoposide. Conclusions: Our results suggest that topoiomerase II-reactive agents may prove to be clinically useful drugs for patients with malignant gliomas. Received: 4 March 1997 / Accepted: 1 June 1997     

Application of Low-Dose Etoposide Therapy for Myelodysplasia Syndromes

The therapy for myelodysplastic syndromes (MDS) and acute leukemia (AL) transformed from MDS is not well established. Etoposide (VP 16-213) at low concentrations shows differentiation-inducing activity against leukemic cells in vitro. A prior study showed that oral low-dose etoposide therapy was effective in patients with chronic myelomonocytic leukemia. We used low-dose etoposide to treat six patients with refractory anemia with excess blasts in transformation (RAEB-t) and seven patients with AL transformed from MDS. The etoposide (50 mg, 2-7 times/week) was usually administered intravenously to ensure reliable bioavailability. Of 12 assessable patients, four RAEB-t patients achieved a partial response and one AL patient achieved complete remission. The responders became transfusion-independent, and this continued for 2-9 months while etoposide therapy was continued. Three of five responders had been resistant to prior repeated low-dose cytarabine therapy. The side effects were mild and well tolerated. Heterogeneous mechanisms were surmised to explain the clinical effects of low-dose etoposide. Several aspects, including the optimal schedule of low-dose etoposide therapy, the effect of this therapy on the patients' survival, the usefulness of combination therapy with other chemotherapeutic drug(s) and/or cytokine(s), should be investigated in the future.     

依立替康联合顺铂与足叶乙甙联合顺铂治疗广泛期小细胞肺癌的系统评价

背景与目的EP(足叶乙甙+顺铂)方案是否是广泛期小细胞肺癌的最佳化疗方案尚不确定,系统评价IP(依立替康+顺铂)方案与EP方案治疗广泛期小细胞肺癌的有效性和安全性。方法计算机检索EMBASE、PubMed、The Cochrane Library、CBM、CSJD、CJFD关于IP方案与EP方案治疗广泛期小细胞肺癌的随机对照试验(RCTS),有两名评价者独立评价纳入研究的质量并提取资料,并用RevMan5.0软件进行meta分析。结果共纳入4篇RCTS共计1180例患者。Meta分析结果显示:IP方案与EP方案治疗广泛期小细胞肺癌在1年生存率(RR=1.22,95%CI:0.97-1.54)、2年生存率(RR=2.26,95%CI:0.46-11.21)方面差异无统计学意义,两方案在总应答率(RR=1.13,95%CI:1.03-1.25)、3/4级中性粒细胞减少症(RR=0.48,95%CI:0.34-0.69)、3/4级血小板减少症(RR=0.23,95%CI:0.15-0.36)、3级贫血(RR=0.55,95%CI:0.40-0.77)、3/4级腹泻(RR=9.56,95%CI:4.91-18.59)...     

Etoposide Protects Mice from Radiation-induced Bone Marrow Death

Etoposide is known to inhibit the activity of topoisomerase II, and to possess radiosensitizing effects. In this paper we show that pretreatment of mice with etoposide one day before whole-body irradiation had a protective effect against radiation-induced bone marrow death. The LD50/30 of mice given radiation alone was 8.26 Gy while that of mice given etoposide one day before whole-body irradiation was 10.35 Gy. The number of endogenous colony-forming units surviving in whole body-irradiated mice was significantly increased by pretreatment with etoposide.     

Etoposide protects mice from radiation-induced bone marrow death

Etoposide is known to inhibit the activity of topoisomerase II, and to possess radiosensitizing effects. In this paper we show that pretreatment of mice with etoposide one day before whole-body irradiation had a protective effect against radiation-induced bone marrow death. The LD50/30 of mice given radiation alone was 8.26 Gy while that of mice given etoposide one day before whole-body irradiation was 10.35 Gy. The number of endogenous colony-forming units surviving in whole body-irradiated mice was significantly increased by pretreatment with etoposide.     

Etoposide and split-dose cisplatin in small-cell lung cancer

Forty-seven untreated patients with small-cell lung cancer (SCLC) were treated with a combination of etoposide (170 mg/m2 intravenously, i.v., days 3-5) and cisplatin (50 mg/m2 i.v., days 1 and 7). Responding patients with limited disease received four cycles followed by irradiation (delivered to the primary site, mediastinum, and supraclavicular region) with 50 Gy. Prophylactic cranial irradiation (PCI) with 30 Gy was performed in patients who achieved complete remission. Responding patients with extensive disease received four to six cycles of chemotherapy. The overall objective response rate (complete response plus partial response, CR + PR) was 94% (44 of 47). CR rate (all patients) was 57% (27 of 47), 51% (19 of 37) in extensive disease and 80% (8 of 10) in limited disease. The median remission duration is 13 months (12 months in extensive disease and 26 months in limited disease). The median survival is 16 months for all patients (15 months in extensive disease, 28 months in limited disease). Mean follow-up is 13 months. Toxicity was primarily hematologic. Twelve of 47 patients had leukopenia of WHO grade 4, 30 of 47 of grade 3. Thrombocytopenia of WHO grade 3 and 4 occurred in 6 of 47 and 2 of 47 patients, respectively. There were four severe infections in neutropenic patients, but no chemotherapy-related lethal complications. The only treatment-related death was that of one patient who died in CR of progressive neurologic dysfunction 11 months after PCI. This schedule of etoposide and cisplatin induces high CR rates and a prolonged survival, especially in patients with extensive disease.     

Etoposide and mitomycin-C in pretreated metastatic breast cancer

Twenty-five patients with metastatic breast cancer in progression after prior chemotherapy +/- hormonotherapy were treated with etoposide 50 mg/m2 i.v. days 1 to 5 every 21 days and mitomycin-C 10 mg/m2 i.v. day 1 every 42 days. A partial response (PR) occurred in 10 patients with an overall response rate of 40% (47% when only the 21 patients evaluable after 3 courses or more were considered). The median duration of PR was 10.5 months (range 3-31). The soft tissue metastatic sites were the most responsive. Toxicity was mild.