DP、EP化疗方案治疗非小细胞肺癌的临床疗效及其对血清血管内皮生长因子的影响

目的对比DP、EP化疗方案治疗非小细胞肺癌（NSCLC）的临床疗效及其对血清血管内皮生长因子（VEGF）的影响。方法102例晚期NSCLC患者随机分为DP组（n=58）和EP组（n=44）。DP组静脉注射多西紫杉醇75mg／m2，dl；静脉滴注顺铂75mg／m2，d1～4；EP组静脉滴注依托泊苷0．1g／d，d1～5；顺铂用法同上。两组28d为1个周期，治疗3个周期，化疗前后常规给予止呕类药物及对症治疗。检测两组临床疗效和血清VEGF水平。结果DP组、EP组，总有效率分别为74．14％和29．55％，DP组总有效率明显高于EP组。与治疗前比较，两组治疗后血清VEGF水平均明显降低。DP组治疗后血清VEGF水平明显低于EP组治疗后。结论DP治疗中晚期NSCLC临床疗效确切，有效率、生存率均较高。     

鬼臼乙叉甙(VP-16)治疗急性白血病

16例急性白血病患者接受鬼臼乙叉甙(VP-16)、阿糖胞苷(Ara-C)的治疗。10例为初治的M_4或M_5患者。5例有效,其中4例为CR,1例PR。另外6例是难治性白血病,包括1例慢粒急变,1例M_6(红-单细胞性),4例第一次或第二次复发者。他们之中仅三例获PR。鬼臼乙叉甙的副作用是骨髓抑制。     

Cisplatin/etoposide/ifosfamide stepwise dose escalation with concomitant granulocyte/macrophage-colony-stimulating factor for patients with far-advanced testicular carcinoma

In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m², etoposide 120–150 mg/m² and ifosfamide 1.2 g/m² for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died ofClostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/l and a thrombocyte nadir of 47000/l. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m², etoposide 150 mg/m² and ifosfamide 1.6 g/m² five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 g/kg on days 6–15. Acute toxicity was severe with a white blood cell nadir of 300/l and thrombocyte nadir of 11 000/l. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure andAspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m², etoposide 200 mg/m² and ifosfamide 1.6 g/m² for 5 days and GMCSF 10 g kg^–1 day^–1 on days 6–15 s.c.Presented at the Satellite Symposium Ifosfamide in Tumor Therapy: Questions for the Nineties; 15th International Cancer Congress, Hamburg, August 16–22, 1990     

High-Dose Etoposide Plus Granulocyte Colony-Stimulating Factor as an Effective Chemomobilization Regimen for Autologous Stem Cell Transplantation in Patients with Non-Hodgkin Lymphoma Previously Treated with CHOP-based Chemotherapy: A Study from the Consortium for Improving Survival of Lymphoma

We conducted a multicenter retrospective study to compare the efficacy and toxicity of various chemomobilization regimens: high-dose (HD) cyclophosphamide, HD etoposide (VP-16), and platinum-based chemotherapies. We reviewed the experiences of 10 institutions with 103 non-Hodgkin lymphoma patients who had previously only been treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. The mobilization yields for each regimen were analyzed. HD VP-16 mobilized a significantly higher median number of CD34⁺ cells (16.22 × 10⁶ cells/kg) than HD cyclophosphamide (4.44 × 10⁶ cells/kg) or platinum-based chemotherapies (6.08 × 10⁶ cells/kg, P < .001). The rate of successful mobilization (CD34⁺ cell count ≥5.0 × 10⁶ cells/kg) was also significantly higher for HD VP-16 (86%) than for HD cyclophosphamide (45%) or platinum-based chemotherapies (61%, P = .004). The successful mobilization rate on day 1 of 72% for HD VP-16 was significantly higher than the rates for HD cyclophosphamide (13%) and platinum-based chemotherapies (26%, P < .001). In multivariate analysis, HD VP-16 was a significant predictor of successful mobilization (P = .014; odds ratio, 5.25; 95% confidence interval, 1.40 to 19.63). Neutropenic fever occurred in 67% of patients treated with HD VP-16. The incidence was similar for HD cyclophosphamide (58%, P = .454) but was significantly lower for platinum-based chemotherapies (12%, P < .001). However, fatal (grade ≥ 4) infection and treatment-related mortality were not observed in this study. In conclusion, the mobilization yield was significantly influenced by the chemomobilization regimen, and HD VP-16 was a highly effective mobilization regimen in patients with non-Hodgkin lymphoma.     

Envafolimab combined with chemotherapy in the treatment of combined small cell lung cancer: A case report

BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy c...     

Phase II Study of Combination Chemotherapy with Etoposide and Ifosfamide in Patients with Heavily Pretreated Recurrent or Persistent Epithelial Ovarian Cancer

The aim of this trial was to investigate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of heavily pretreated recurrent or persistent epithelial ovarian cancer (EOC). Patients with recurrent or persistent EOC who had measurable disease and at least two prior chemotherapy participating in this phase II trial were to receive etoposide at a dose of 100 mg/m²/day intravenously (IV) on days 1 to 3 in combination with ifosfamide 1 g/m²/day IV on days 1 to 5, every 21 days. Thirty-seven patients were treated; about 78% had previously received more than two separate regimens. The response rate (RR) was 18.9% and median duration of response was 7 months (range, 1-15). Treatment free interval prior to ETI (TFI) has significant correlation with RR rate (P=0.034). Patients (n=6) with TFI ≥6 months had 50% of RR, while patients (n=31) with TFI <6 months had 12.9%. Median survival was 9 months at a median follow-up of 9.2 months. Grade 3 or 4 toxicities included neutropenia in 20.1% of the 139 cycles of ETI, anemia in 7.2% and thrombocytopenia in 8.6%. The ETI produces relatively low toxicity and modest activity in heavily pretreated recurrent or persistent EOC. This is significant in patients with TFI ≥6 months.     

In vivo inhibition of etoposide-mediated apoptosis,toxicity, and antitumor effect by the topoisomerase II-uncoupling anthracycline aclarubicin

A number of clinically important drugs such as the epipodophyllotoxins etoposide (VP-16) and teniposide (VM-26), the anthracyclines daunorubicin and doxorubicin (Adriamycin), and the aminoacridine amsacrine exert their cytotoxic action by stabilizing the cleavable complex formed between DNA and the nuclear enzyme topoisomerase II. We have previously demonstrated in several in vitro assays that the anthracycline aclarubicin (aclacinomycin A) inhibits cleavable-complex formation and thus antagonizes the action of drugs such as VP-16 and daunorubicin. The present study was performed to validate these in vitro data in an in vivo model. At nontoxic doses of 6 and 9 mg/kg, aclarubicin yielded a marked increase in the survival of non-tumor-bearing mice given high doses of VP-16 (80–90 mg/kg) in six separate experiments. In therapy experiments on mice inoculated with Ehrlich ascites tumor cells, aclarubicin given at 6 mg/kg roughly halved the increase in median life span induced by VP-16 at doses ranging from 22 to 33 mg/kg. An attempt to determine a more favorable combination of VP-16 and aclarubicin by increasing VP-16 doses failed, as the two drugs were always less effective than VP-16 alone. The way in which VP-16-induced DNA strand breaks lead to cell death remains unknown. However, VP-16 has been reported to cause apoptosis (programmed cell death) in several cell lines. To ascertain whether the protection given by aclarubicin could have a disruptive effect on the apoptotic process, we used the small intestine as an in vivo model. Whereas VP-16-induced apoptosis in crypt stem cells was detectable at a dose as low as 1.25 mg/kg, aclarubicin given at up to 20 mg/kg did not cause apoptosis. Indeed, aclarubicin caused a statistically significant reduction in the number of cells rendered apoptotic by VP-16. The present study thus confirms the previous in vitro experiments and indicates the value of including an in vivo model in a preclinical evaluation of drug combinations.This work was supported by the Danish Cancer Society     

In vitro and in vivo Effects of Cisplatin and Etoposide in Combination on Small Cell Lung Cancer Cell Lines

The effects of cisplatin (CDDP) and etoposide (ETP) in combination were evaluated in vitro and in vivo using small cell lung cancer cell lines. The combination effects in vitro were investigated using isohologram analysis. Used together, CDDF and ETP showed a synergistic effect against cell growth on only 1 cell line (SBC-3), additive effects on 6 (SBC-2, SBC-5, Lul30, Lul34AH, Lul35T and H69) and an antagonistic effect on 1 (SBC-1). In the in vivo experiment, nude mice were inoculated with SBC-1, SBC-3 and SBC-5 cells. Two or 5 mgAg CDDP and 10 or 30 mgAg ETP were administered intraperitoneally alone and simultaneously in combination to nude mice. The in vivo effects of the combination were determined by comparing the observed growth ratio in mice treated with the combination with the expected value of this ratio calculated based on the assumption that the effects of the drugs were simply additive. According to this definition, synergistic effects were observed against all 3 tumors. Thus, the in vivo and in vitro effects differed. The toxicity of the combination therapy, which was analyzed by estimating the body weight change of mice, was no higher than that of CDDP or ETP alone. These results suggest that the excellent clinical effects of CDDP and ETP combination therapy may he attributable not to drug interaction at the cellular level hut to the feasibility of combined use of them at full doses without overlapping side effects.     

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.     

Is there a circadian variation in plasma concentrations of etoposide given by prolonged continuous infusion?

 The prolonged continuous infusion of low-dose etoposide is a new approach to treating cancer. Whether or not a circadian variation in the plasma levels of etoposide existed was investigated in nine patients with non-small-cell lung cancer. Etoposide was infused for 14 days and blood samples were obtained every 4 h for 1 day. There was no significant circadian variation, and the observed small within-day variations seemed to lack clinical significance. Received: 24 March 1995 / Accepted: 2 August 1995