Study Of Etoposide Research Articles

LBA61 Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): 3-year overall survival update from the phase III CASPIAN study

In CASPIAN, the Phase 3 study of etoposide + cisplatin/carboplatin (EP) ± durvalumab (D) ± tremelimumab (T) as first-line treatment of ES-SCLC, D + EP demonstrated a statistically significant improvement in OS vs EP alone (data cut-off [DCO]: 11 Mar 2019; HR 0.73 [95% CI 0.59–0.91; p=0.0047]). In a subsequent analysis after a median follow-up of 25.1 mo (DCO 27 Jan 2020), OS benefit with D + EP vs EP was sustained (HR 0.75 [95% CI 0.62–0.91; nominal p=0.0032]), and D + T + EP numerically improved OS vs EP (HR 0.82 [95% CI 0.68–1.00; p=0.0451]), but did not reach statistical significance (p≤0.0418).

Phase II Study of Etoposide and Cisplatin With Concurrent Twice-Daily Thoracic Radiotherapy Followed by Irinotecan and Cisplatin in Patients With Limited-Disease Small-Cell Lung Cancer: West Japan Thoracic Oncology Group 9902

Phase II Study of Etoposide and Cisplatin With Concurrent Twice-Daily Thoracic Radiotherapy Followed by Irinotecan and Cisplatin in Patients With Limited-Disease Small-Cell Lung Cancer: West Japan Thoracic Oncology Group 9902

Pharmacokinetic modulation of oral etoposide by ketoconazole in patients with advanced cancer

Etoposide is a widely used cytotoxic drug that is commercially available in both intravenous and oral formulations. High interpatient pharmacokinetic variability has been associated with oral etoposide administration. Various strategies used in the past to reduce such variability have not been successful. Hence, this study was designed to evaluate if pharmacokinetic modulation of oral etoposide with ketoconazole could lead to a favorable alteration of etoposide pharmacokinetics, and to assess the feasibility and safety of this approach. Thirty-two patients were treated with ketoconazole 200 mg daily with an escalating dose of oral etoposide starting at a dose of 50 mg every other day. Pharmacokinetic samples were obtained during the first treatment cycle after the administration of an oral etoposide and ketoconazole dose. Additional baseline pharmacokinetic studies of etoposide alone were performed 4 days prior to the first treatment cycle. Dose limiting toxicities were neutropenia and fatigue. Ketoconazole increased the area under the plasma concentration-time curve (AUC) of oral etoposide by a median of 20% (p < 0.005). Ketoconazole did not reduce the interpatient variability in etoposide pharmacokinetics. Pretreatment bilirubin levels correlated with etoposide clearance (Spearman's r = -0.48, p = 0.008). The maximum tolerated dose was etoposide administered at 50 mg daily and ketoconazole 200 mg qd for 3 of 5 weeks. Ketoconazole reduces the apparent clearance of oral etoposide, does not alter its toxicity profile and does not reduce interpatient pharmacokinetic variability. Other methods to reduce the pharmacokinetic variability of oral etoposide are needed.

Etoposide, vincristine, and cyclosporin A with standard‐dose radiation therapy in newly diagnosed diffuse intrinsic brainstem gliomas: A pediatric oncology group phase I study

Brainstem gliomas (BSGs) are resistant to all therapy. Based on their imaging characteristics, we postulated that inhibition of P-glycoprotein (P-gp) associated with endothelial cells of the blood-brain barrier might enhance penetration of xenobiotic antineoplastics. Seven patients were enrolled in a Phase I study of etoposide, continuous infusion cyclosporine A given with and escalating doses of vincristine and concomitant standard-dose irradiation. Six patients were entered at the first level and one at the second. Closure of the study was mandated by dose-limiting neurotoxicity, consisting of seizures associated with white-matter changes, and alteration of consciousness with bulbar signs. One patient had tumor necrosis at 6 weeks, suggesting some tumor effect. Median survival for the group was 11 months, and for the patients who completed more than 1 month of therapy it was 11 months. This regimen proved excessively toxic.

Phase I study of etoposide, cisplatin and irinotecan triplet in patients with advanced-stage small-cell lung cancer

The irinotecan-cisplatin combination has emerged as a new standard for the treatment of advanced-stage small-cell lung cancer (AS-SCLC). To move forward we developed a 3-day regimen of cisplatin, etoposide and irinotecan. Successive cohorts of AS-SCLC patients were treated with irinotecan administered as a single 1-h infusion in combination with fixed doses of cisplatin (20 mg/m(2)) and etoposide (75 mg/m(2)), both given for three consecutive days (ECI regimen). Irinotecan dose was escalated from 60 mg/m(2) by 40-mg/m(2) increments. At mid-step between the maximum tolerated dose (MTD) and the previous dose level, patients were randomized for the day of administration of irinotecan (day 1 vs day 3). A total of 36 AS-SCLC patients received 166 courses of treatment at four dose levels. The MTD of irinotecan was 140 mg/m(2) (three dose-limiting toxicities, DLTs), and the recommended optimal dose (ROD) 120 mg/m(2) (two DLTs). DLTs were febrile neutropenia and grade 3 diarrhea. Other toxicities were mild. No difference in toxicity was seen between the two time schedules. A 77% (95% CI 63.25-90.75%) response rate was recorded among 31 evaluable patients and the median survival was 12 months. The ECI regimen was well tolerated and showed considerable activity in patients with AS-SCLC. Phase II/III evaluation is ongoing.

Pharmacokinetics of etoposide with intravenous drug administration in children and adolescents

Pharmacokinetics of etoposide in Japanese children and adolescents has not been investigated. The objectives of the present study were (i) to document the pharmacokinetics of etoposide in Japanese children; (ii) to determine the intra- and interpatient variability in systemic etoposide exposure and (iii) to obtain insights into the age-pharmacokinetic parameter relationship. Pharmacokinetic studies of etoposide, given at doses of 60-200 mg/m2 by intravenous (i.v.) route of administration, were conducted in 18 children and adolescents (aged <19 years) with malignant diseases. High performance liquid chromatography was used to measure the blood etoposide levels. Pharmacokinetic parameters (mean~SD) of the 14 patients (24 courses) who received etoposide 100 mg/m2 were as follows: peak serum concentration (Cmax), 18.5~6.4 microg/mL; trough serum concentration, 0.2~0.1 microg/mL; biological half-life (T1/2), 3.6~0.7 h; volume of distribution (Vd), 6.3~3.4 L/m2; area under the etoposide serum concentration-time curve (AUC), 129~38 hr x microg/mL; systemic clearance, 21.1~10.8 mL/min per m2. The T1/2, Vd, and AUC were not associated with age. An increase in etoposide dose per body surface area (BSA) was associated with increase in its Cmax and area under the time-concentration curve (AUC). Wide interpatient variability in these parameters was demonstrated. The present study demonstrated that: (i) Pharmacokinetics of etoposide in Japanese children and adolescents were similar to those in Caucasians. (ii) Increased exposure to etoposide was associated with the Cmax. A clear correlation between Cmax and AUC was also found. (iii) Selecting the dose of etoposide according to body surface area (BSA) might give an acceptable range of exposure for children more than 1 year of age.

Pulse radiolysis studies of etoposide and 4′-demethylepipodophyllotoxin in aqueous solution

Abstract The reactions of etoposide (VP 16, 4′-demethyl-epipodophyllotoxin ethylidene- β - d -glucoside) and 4′-demethylepipodophyllotoxin (DMEP) with the primary radiolytic products of water, such as e − aq , H and OH/O − radicals, and the secondary radical (SO − 4 ) in aqueous solution were studied by use of the techniques of pulse radiolysis, respectively. The absorption spectra of reaction products with e − aq , H and OH/O − and SO − 4 radicals were observed, and the rate constants of them were determined by following the build-up kinetics of radicals produced or the decay of hydrated electron observed at 600 nm, respectively.

A Feasibility, Toxicity, and Early Response Study of Etoposide, Ifosfamide, and Vincristine for the Treatment of Children with Rhabdomyosarcoma

A Feasibility, Toxicity, and Early Response Study of Etoposide, Ifosfamide, and Vincristine for the Treatment of Children with Rhabdomyosarcoma

Mass Spectral Study of Etoposide

Mass Spectral Study of Etoposide

Mass Spectral Study of Etoposide

The antitumour agent etoposide has been studied under electron impact, chemical ionization and liquid secondary ion mass spectral conditions. The major fragment ions are found to be due to the cleavage of C4–O, C4O–glycoside and C1–C′1 bonds. These fragmentation pathways are established by collision-induced dissociation and accurate mass measurement. Mass spectral studies of 4′-demethylepipodophyllotoxin, epipodophyllotoxin and their respective p-fluoroanilidine derivatives were also carried out.

Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer.

To determine the maximum-tolerated dose (MTD) and toxicity of PSC 833 infusion administered with etoposide for 5 days in patients with cancer, and to determine the effect of PSC 833 on etoposide pharmacokinetics. Thirty-five patients were entered onto the study, one of whom was ineligible. Etoposide was delivered from day 1 as a 2-hour infusion over 5 consecutive days at a dose of 75 to 100 mg/m2/d. PSC 833 was administered from day 2 as a 2-hour loading dose and as a 5-day continuous infusion. Doses were escalated from 1 to 2 mg/kg (loading dose) and 1 to 15 mg/kg/d (continuous infusion). Thirty-four patients were treated with 53 cycles of PSC 833 and etoposide. Steady-state blood PSC 833 levels more than 1,000 ng/mL were achieved in all patients treated at PSC 833 doses > or = 6.6 mg/kg/d by continuous infusion. Myelosuppression was the most common toxicity. The major dose-related toxicity of PSC 833 was reversible hyperbilirubinemia, which occurred in 83% of cycles. The dose-limiting toxicity of PSC 833 was severe ataxia, which occurred in two of nine patients treated at 12 mg/kg/d and in both of the single patients treated at 13.5 and 15 mg/kg/d. PSC 833 concentrations more than 2,000 ng/mL resulted in an increase in etoposide area under the curve (AUC) of 89%, a decrease in etoposide clearance (Cl) of 45%, a decrease in volume of steady-state distribution (Vss) of 41%, and an insignificant increase in alpha half-life (t 1/2 alpha) and significant increase of beta half-life (t 1/2 beta) of 19% and 77%, respectively. PSC 833 can be administered in combination with etoposide with acceptable toxicity. The recommended continuous infusion dose of PSC 833 for this schedule is 10 mg/kg/d over 5 days. PSC 833 results in an increase in etoposide exposure and etoposide doses should be reduced in patients receiving PSC 833.

Phase I study of etoposide in combination with cisplatin and granulocyte colony stimulating factor (G-CSF) in patients with non small cell lung cancer (NSCLC) : T. Nakabayashi 1, M. Harada 1 S. Sasaki 2, H. Tamura 2, T. Fujikane 3, T. Shimizu 3, F. Kisi 4, S. Fujiuchi 5, H. Akita 6, H. Miyamoto 6, Y. Kawakami 6. Sapporo National

Phase I study of etoposide in combination with cisplatin and granulocyte colony stimulating factor (G-CSF) in patients with non small cell lung cancer (NSCLC) : T. Nakabayashi 1, M. Harada 1 S. Sasaki 2, H. Tamura 2, T. Fujikane 3, T. Shimizu 3, F. Kisi 4, S. Fujiuchi 5, H. Akita 6, H. Miyamoto 6, Y. Kawakami 6. Sapporo National

Pharmacologic Study of Etoposide and Cisplatin by the Intraperitoneal Route

Based on the previous demonstration of a high peritoneal-to-plasma ratio of drug exposure for intraperitoneal (IP) etoposide, the authors performed a clinical/pharmacokinetic trial of etoposide (600 mg/m2) in combination with cisplatin (100 mg/m2). The drugs were administered concurrently IP, and allowed to dwell for 4 hours, after which the peritoneum was drained. Six patients received 13 cycles of treatment. Grade 4 neutropenia occurred in three patients; toxicity was otherwise moderate. Plasma etoposide concentrations reached a peak at 4.2 +/- 2.5 hours and declined exponentially with a terminal half-life of 9.5 +/- 3.6 hours. Peritoneal etoposide concentrations declined monoexponentially with a half-life of 3.7 +/- 2.6 hour. The calculated peritoneal-to-plasma ratio of unbound etoposide was 35. The plasma and peritoneal half-lives of ultrafilterable cisplatin were 21.7 +/- 14.1 hours and 1.8 +/- 0.7 hours, respectively. The peritoneal/plasma area under curve AUC ratio was 18.3. These pharmacokinetic indices for both drugs are consistent with those obtained with the use of each drug as a single agent. Thus, the concomitant use of one does not alter the pharmacokinetic activity of the other. The high AUC ratios support the further clinical development of these drugs in combination in the intraperitoneal setting.

A phase II study of etoposide combined with ifosfamide as second-line therapy in cisplatin-resistant ovarian carcinomas

The response rate and survival obtained with the second-line chemotherapeutic regimen etoposide combined with ifosfamide were analyzed in a series of 32 patients progressing or relapsing after cisplatin-based front-line treatment. Etoposide (100 mg/m2) was given i.v. for 3 days and 1.0 g/m2 i.v. ifosfamide, for 5 days, with 200 mg/m2 mesna being given i.v. at 0, 4, and 8 h after ifosfamide. The median age of the patients was 53.5 years (range, 26-72 years). In all, 32 patients were evaluable for toxicity and 29, for response; all patients had measurable lesions and all had previously received cisplatin-based chemotherapy. The overall objective response rate was 21%; the median duration of response was 6+ months (range, 2(+)-11 months), with that for stable disease being 5 months (range, 2-9+). The only patient who achieved a complete response is still alive after 13 months. The median survival for partial responders was 9+ months (range, 4(+)-13), and that for stable disease was 6+ months (range, 3(+)-14+). No major toxicity was observed, but myelosuppression caused dose reduction in 50% of the patients. Although the median follow-up time was short, this combination produced relatively low toxicity, with a 21% objective response rate in second-line chemotherapy after cisplatin failure, which means that this regimen is not cross-resistant to cisplatin.

A Phase II Study of Etoposide in Patients with Hepatocellular Carcinoma by the Tokyo Liver Cancer Chemotherapy Study Group

Twenty-four patients with hepatocellular carcinoma were treated with 80 mg etoposide/m2 for five consecutive days at 4-week intervals. Of the 21 patients evaluated, only one showed a partial response (of 8 weeks, duration). The dose-limiting factor was bone marrow suppression. Grades 3 and 4 white blood cell count toxicity occurred in five (24%) and two (10%) patients, respectively. Alopecia (grades 1 and 2) was observed in 18 patients (57%). The The present study indicates that etoposide has very limited activity against hepatocellular carcinoma.

High-dose etoposide for meningeal carcinomatosis in patients with small cell lung cancer

INTRODUCTION IN A high percentage of SCLC patients, central nervous system (CNS) metastases are found and this usually results in considerable morbidity and mortality [ 11. This is especially the case in patients with meningeal carcinomatosis (MC). The incidence of MC in SCLC has been reported to be between 5 and 18%. With prolongation of survival , the chance of MC becoming symptomatic is rapidly increasing [ 11. The results of therapy for this devastating form of metastatic disease have been rather poor. After high-dose cyclophosphamide and etoposide with autologous bone marrow transplantation [2] and in a phase I study of etoposide [3], favourable responses of brain metastases from SCLC were found. In this report we describe the effect of highdose etoposide (HDE) in five patients with MC from SCLC.

Phase 2 Study of High Dose Etoposide (VP16-213) in Hepatocellular Carcinoma

A phase II study of etoposide (VP16-213) in hepatocellular carcinoma was conducted among 18 Chinese patients. There was no observable tumour response but the treatment was relatively well tolerated with an overall median survival interval of 74 days.

Activity and distribution studies of etoposide and mitozolomide in vivo and in vitro against human choriocarcinoma cell lines.

The in vivo antitumor activity of etoposide and mitozolomide was assessed in nude mice bearing a xenograft (CC3) of human gestational choriocarcinoma. Both agents demonstrated, at best, marginal activity observed as a delay in tumour growth. This lack of sensitivity suggests that the CC3 xenograft is not a good model for selection of agents for clinical evaluation in gestational choriocarcinoma. Plasma and tissue concentrations of etoposide and mitozolomide were measured in nude mice. Drug concentrations found in tumour tissue were 60% and 30% of plasma levels for mitozolomide and etoposide respectively. Etoposide and mitozolomide activity was also evaluated in vitro with another choriocarcinoma cell line (JAR). Maximum cell-kill was achieved after exposure to etoposide 0.05-1 microgram/ml for 3-24 h. In vitro response to etoposide demonstrates the importance of exposure time in determining cytotoxicity. In contrast, mitozolomide at concentrations from 1-100 micrograms/ml did not have a marked effect against JAR after exposure for 3-24 h.

Drug therapy of the non-small cell bronchial carcinoma with high dose VP 16: A dose-finding study of etoposide in combination with cisplatin

Drug therapy of the non-small cell bronchial carcinoma with high dose VP 16: A dose-finding study of etoposide in combination with cisplatin

A phase II study of etoposide and splitted doses of CDDP for the treatment of non small cell lung cancer

A phase II study of etoposide and splitted doses of CDDP for the treatment of non small cell lung cancer