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At least 19 recordsLinked to original sources
PubMed1997

Randomized comparison of etoposide pharmacokinetics after oral etoposide phosphate and oral etoposide.

Etoposide phosphate is a water-soluble prodrug of etoposide. The plasma pharmacokinetics of etoposide following oral administration of etoposide phosphate or oral etoposide were compared. Seventeen patients with solid tumours were enrolled to receive oral etoposide phosphate 125 mg m(-2) on days 1-5 every 3 weeks, with escalation to 175 mg m(-2) from course 3 when possible. Patients were randomized to receive oral etoposide phosphate or oral etoposide on day 1 of course 1 and the alternative compound on day 1 of course 2. Fifteen patients received two or more courses and were evaluable for pharmacokinetic comparisons. The median AUC(inf) (area under the concentration vs time curve from zero to infinity) of etoposide was 77.7 mg l(-1) h after etoposide phosphate (95% CI 61.3-100.5) and 62.0 mg l(-1) h after oral etoposide (95% CI 52.2-76.9). The difference in favour of etoposide phosphate was borderline significant: median 9.9 mg l(-1) h (95% CI 0.1-32.8 mg l(-1) h; P = 0.05). However, the inter-patient variability of etoposide AUC(inf) was not improved (coefficients of variation 42.3% and 48.4%). Etoposide phosphate was undetectable in plasma after oral administration. Toxicities of oral etoposide phosphate were not different from those known for etoposide. In conclusion, oral etoposide phosphate does not offer a clinically relevant benefit over oral etoposide.

Administration, Oral↗
PubMed1995

Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors.

PURPOSE: To assess the pharmacokinetics and bioequivalence of etoposide following intravenous (i.v.) administration of etoposide phosphate (Etopophos; Bristol-Myers Squibb, Princeton, NJ), a prodrug of etoposide, and VePesid (Bristol-Myers Squibb). PATIENTS AND METHODS: Forty-nine solid tumor patients were randomized to receive Etopophos or VePesid on day 1 of a day-1,3,5 schedule of treatment. The alternate drug was given on day 3 and repeated on day 5. The dose, 150 mg/m2 of etoposide equivalent, was administered by constant rate infusion over 3.5 hours. The plasma concentrations of etoposide phosphate and etoposide were determined using validated high-performance liquid chromatography (HPLC) assays. Pharmacokinetic parameters were calculated by a noncompartmental method. Etopophos was considered to be bioequivalent to VePesid if the 90% confidence limits for the differences in mean maximum concentration (Cmax) and AUCinf of etoposide were contained within 80% to 125% for the long-transformed data. RESULTS: Forty-one patients were assessable for pharmacokinetics and bioequivalence assessment. Following i.v. administration, etoposide phosphate was rapidly and extensively converted to etoposide in systemic circulation, resulting in insufficient data to estimate its pharmacokinetics. The mean bioavailability of etoposide from Etopophos, relative to VePesid, was 103% (90% confidence interval, 99% to 106%) based on Cmax, and 107% (90 confidence interval, 105% to 110%) based on area under the concentration versus time curve from zero to infinity (AUCinf) values. Mean terminal elimination half-life (t1/2), steady-state volume of distribution (Vss), and total systemic clearance (CL) values of etoposide were approximately 7 hours, 7 L/m2, and 17 mL/min/m2 after Etopophos and VePesid treatments, respectively. The main toxicity observed was myelosuppression, characterized by leukopenia and neutropenia. CONCLUSION: With respect to plasma levels of etoposide, i.v. Etopophos is bioequivalent to i.v. VePesid.

Adult↗
PubMed1995

Etoposide phosphate or etoposide with cisplatin in the treatment of small cell lung cancer: randomized phase II trial.

Etoposide phosphate, a water soluble prodrug of etoposide, has several potential advantages including easier and more rapid administration, avoidance of large fluid loads, and elimination of hypersensitivity reactions and other problems related to the solubilizer. This randomized Phase II study was done to evaluate the efficacy and toxicity of etoposide phosphate and etoposide, when used in combination with cisplatin in the treatment of patients with small cell lung cancer. Previously untreated small cell lung cancer patients were randomized to receive cisplatin in combination with molar equivalent does of either etoposide or etoposide phosphate. The patients were evaluated with respect to response rate, time to progression, survival, and toxicity. Response rates with etoposide phosphate and etoposide were 61% (95% confidence interval 55-67%) and 58% (95% confidence interval 52-64%), respectively (P = 0.85). Median time to progression was 6.9 months for patients who received etoposide phosphate and 7.0 months for those with etoposide (P = 0.50). For extensive stage disease patients, median survival with etoposide phosphate was 9.5 months versus 10 months for etoposide (P = 0.93). The corresponding median survivals for patients with limited stage disease were > 16 months and 17 months, respectively (P = 0.62). Myelosuppression was the most common toxicity; Grade 3 and 4 leukopenia occurred in 63% of patients receiving etoposide phosphate compared with 77% receiving etoposide (P = 0.16). The combination of etoposide phosphate and cisplatin is effective in the treatment of small cell lung cancer, and can be administered with acceptable toxicity. This study was not designed to be a formal Phase III comparative trial, but the efficacy and toxicity observed with this regimen were found to be similar to a standard etoposide/cisplatin regimen, using molar equivalent etoposide doses. Etoposide phosphate is preferable to etoposide because it is easier to use.

Antineoplastic Agents↗
PubMed2001

Bioequivalence investigation of high-dose etoposide and etoposide phosphate in lymphoma patients.

PURPOSE: To compare etoposide pharmacokinetics following administration of high-dose etoposide and etoposide phosphate, a water-soluble prodrug of etoposide. Bioequivalence was assessed using a two-treatment randomized crossover design. METHODS: Ten patients with high-risk or relapsed lymphoma were treated with a sequential high-dose chemotherapy. They were randomized to receive either 3 x 400 mg/m2 etoposide or an equimolar amount of etoposide phosphate (as 1-h infusions on three consecutive days) in the first course and the alternative drug in the second course. Serial plasma and ultrafiltered plasma samples were collected and analysed for etoposide by a reversed-phase HPLC method with UV and electrochemical detection. Pharmacokinetic parameters were estimated using a two-compartment model. Bioequivalence was assessed calculating the 90% confidence intervals (CI) for the ratios of the geometric means of AUC(0-infinity) and additionally of Cmax of etoposide derived from etoposide phosphate relative to etoposide in plasma and ultrafiltered plasma as point estimates (level of significance alpha < 0.05). RESULTS: Pharmacokinetic parameters of etoposide were comparable in both treatment arms except that terminal half-life was significantly shorter and apparent Vss in ultrafiltered plasma was significantly larger following administration of the prodrug. The point estimates for AUC(0-infinity) of etoposide derived from etoposide phosphate relative to etoposide were 102.9% and 88.4% for plasma and ultrafiltered plasma, respectively. The 90% CIs were in the range from 80% to 125% where bioequivalence can be assumed. The point estimates of Cmax on day 3 of chemotherapy were 96.5% and 81.7% in plasma and ultrafiltrate with the 90% CI in ultrafiltered plasma being out of the range from 80% to 125%. CONCLUSION: With respect to total drug exposure, represented by AUC(0-infinity), high-dose etoposide phosphate is bioequivalent to high-dose etoposide.

Adult↗
PubMed1996

Effects of gender, age, and race on the pharmacokinetics of etoposide after intravenous administration of etoposide phosphate in cancer patients.

The influence of gender, age, and race on the pharmacokinetics of etoposide and on the extent of conversion of etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) to etoposide are summarized. Included in the integrated statistical analyses were 192 patients from six phase I/II studies (102 men and 90 women, 128 aged < or = 65 years and 64 aged > 65 years; 134 were white, 18 were other races, and race was not recorded for 40). The dose of etoposide phosphate ranged from 25 to 200 mg/m2 of etoposide equivalents and was administered as 5-(bolus) to 210-minute intravenous infusions. Total body clearance of etoposide was comparable between men and women. However, significantly lower steady-state volumes of distribution and shorter half-lives were observed in women relative to men. Patients who were older than 65 years had significantly lower etoposide total body clearance and longer half-lives than younger patients. The gender- and age-related differences observed in the pharmacokinetic parameters of etoposide were significant but generally of a small magnitude (< or = 13%), indicating no need for dose adjustment in these patient populations. There were no significant race-related differences in the pharmacokinetic parameters of etoposide. All patients showed rapid conversion of etoposide phosphate to etoposide. The individual area under the plasma concentration-time curve ratio of etoposide phosphate/etoposide was < or = 0.0324, indicating that etoposide was the major circulating moiety after infusion of etoposide phosphate. Significant gender-, age-, or race-related differences in the area under the plasma concentration-time curve ratios were not observed. An evaluation of the area under the plasma concentration-time curve ratios with respect to infusion time suggested that the conversion of etoposide phosphate to etoposide was independent of infusion time.

Adult↗
PubMed1994

Phase I evaluation of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on days 1, 3, and 5 in patients with solid tumors.

PURPOSE: To determine the toxicities, maximum-tolerated dose (MTD), and pharmacology of etoposide phosphate, a water-soluble etoposide derivative, administered as a 5-minute intravenous infusion on a schedule of days 1, 3, and 5 repeated every 21 days. PATIENTS AND METHODS: Thirty-six solid tumor patients with a mean age of 63 years, performance status of 0 to 1, WBC count > or = 4,000/microL, and platelet count > or = 100,000/microL, with normal hepatic and renal function were studied. Doses evaluated in etoposide equivalents were 50, 75, 100, 125, 150, 175, and 200 mg/m2/d. Etoposide in plasma and urine and etoposide phosphate in plasma were measured by high-performance liquid chromatography (HPLC). Eleven of 36 patients were treated with concentrated etoposide phosphate at 150 mg/m2/d. RESULTS: Grade I/II nausea, vomiting, alopecia, and fatigue were common. Leukopenia (mainly neutropenia) occurred at doses greater than 75 mg/m2, with the nadir occurring between days 15 and 19 posttreatment. All effects were reversible. Hypotension, bronchospasm, and allergic reactions were not observed in the first 25 patients. The MTD due to leukopenia was determined to be between 175 and 200 mg/m2/d. In 11 patients treated with concentrated etoposide phosphate, no local phlebitis was noted, but two patients did develop allergic phenomena. The conversion of etoposide phosphate to etoposide was not saturated in the dosages studied. Etoposide phosphate had peak plasma concentrations at 5 minutes, with a terminal half-life (t1/2) of 7 minutes. Etoposide reached peak concentrations at 7 to 8 minutes, with a t1/2 of 6 to 9 hours. Both etoposide phosphate and etoposide demonstrated dose-related linear increases in maximum plasma concentration (Cmax) and area under the curve (AUC). CONCLUSION: Etoposide phosphate displays excellent patient tolerance in conventional dosages when administered as a 5-minute intravenous bolus. The suggested phase II dose is 150 mg/m2 on days 1, 3, and 5. The ability to administer etoposide phosphate as a concentrated, rapid infusion may prove of value both in the outpatient clinic and in high-dose regimens.

Adult↗
PubMed1995

Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer.

PURPOSE: This randomized phase II study evaluated the efficacy and toxicity of etoposide phosphate when used in combination with cisplatin in the treatment of small-cell lung cancer. PATIENTS AND METHODS: Patients with previously untreated small-cell lung cancer were randomized to receive cisplatin in combination with either etoposide or etoposide phosphate. Molar-equivalent doses of etoposide and etoposide phosphate were used. Response rate, time to progression, survival, and toxicity were compared. RESULTS: Major response rates with etoposide phosphate and etoposide were 61% (95% confidence interval, 55% to 67%) and 58% (95% confidence interval, 52% to 64%), respectively (P = .85). No significant differences in median time to progression or survival were observed in patients who received etoposide phosphate versus etoposide. Grade 3 and 4 leukopenia occurred in 63% of patients who received etoposide phosphate compared with 77% who received etoposide (P = .16). CONCLUSION: The combination of etoposide phosphate and cisplatin is effective in the treatment of small-cell lung cancer, and can be administered with acceptable toxicity. Although this study was not designed to be a formal comparative trial, the efficacy and toxicity observed with this regimen were found to be similar to a standard etoposide/cisplatin regimen, using molar-equivalent etoposide doses. Because of its greater ease of administration, etoposide phosphate is preferable to etoposide for routine clinical use.

Aged↗
PubMed1996

Etoposide combined with interferon alfa-2b: novel exploitation of established etoposide pharmacokinetics and pharmacodynamics.

PURPOSE: To construct an efficient pilot study design to determine whether interferon alfa-2b modifies the pharmacokinetics and pharmacodynamics of continuous-infusion etoposide. PATIENTS AND METHODS: A two-stage randomized 2 X 2 factorial design was used to evaluate interferon alfa-2b at two doses (2 or 10 MU/m2/day SQ for 3 days) and two schedules (interferon alfa-2b administered before or concurrent with 72-hour continuous-infusion etoposide). Etoposide was administered at 75, 100, or 125 mg/m2/day. In lieu of comparing the experimental arms to an etoposide-alone control arm to determine effect of interferon alfa-2b dose and schedule, a novel analytic approach was used. The effect of interferon alfa-2b on etoposide-induced leukopenia was assessed indirectly by comparison of the observed white blood cell (WBC) nadir to the nadir predicted from an established pharmacodynamic model for single agent etoposide. RESULTS: Based on 29 patients, dose-normalized 24-hour total and estimated free etoposide concentrations did not differ with interferon alfa-2b dose or schedule. Patients treated with interferon alfa-2b before etoposide had, on average a WBC nadir 545 +/- 225 cells microliter lower than that predicted by a pharmacodynamic model for etoposide alone. An optimal nonlinear model for leukopenia was defined by interferon alfa-2b schedule in addition to 24-hour etoposide concentration. CONCLUSION: A novel study design and statistical analysis provided an efficient preliminary evaluation of the combination of interferon alfa-2b with etoposide in a modest number of patients. Exploitation of a previously validated pharmacodynamic model allowed evaluation of interferon alfa-2b effect and eliminated the need for an etoposide-alone control arm. The pharmacokinetics of continuous-infusion etoposide at doses from 75 to 125 mg/m2/day appear to be unchanged by interferon alfa-2b at the doses and schedules tested and the combination appears to be feasible. We hypothesize that leukopenia may be enhanced when interferon alfa-2b is administered before etoposide, especially at a higher dose of interferon alfa-2b.

Adult↗
PubMed1996

A pharmacoeconomic evaluation of cisplatin in combination with either etoposide or etoposide phosphate in small cell lung cancer.

To compare etoposide and etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) in maximizing the cost efficiency of care for patients with small cell lung cancer (SCLC), we obtained pharmacoeconomic data from a phase II randomized study of these agents. This clinical investigation assessed the efficacy and toxicity of etoposide phosphate combined with cisplatin in treating SCLC. In the economic analysis, we identified resources expended during chemotherapy and related concomitant procedures and matched them with the current procedure terminology level of costs for the provider and the payor. The valuation process was conducted in the specific point-of-care (outpatient v inpatient) setting. The appropriate pharmacoeconomic analytic tool used when comparators are considered to achieve equivalent clinical outcomes is cost-minimization analysis. We provide the cost-minimization analysis from two oncology care perspectives: the provider and the payor. In addition, a payor/ provider cost reduction model was constructed to illustrate the potential economic effects achieved through more efficient use of the outpatient chemotherapy facility due to the ease of administration of etoposide phosphate. The provider's average cost per patient for treating an SCLC patient for six cycles in US dollars is $26,764.48 for etoposide versus $26,026.70 for etoposide phosphate. The payor's average treatment cost per patient for treating an SCLC patient for six cycles for the respective regimens was $34,270.65 and $34,320.70. When the time savings associated with the etoposide phosphate regimen are applied to the outpatient chemotherapy facility, the adjusted average treatment costs per patient for the payor are $2,797.29 less than the costs for using the standard etoposide intravenous formulation. Delivering an etoposide phosphate regimen accrued adjusted savings of $2,897.03 per patient. Based on these results, etoposide phosphate is a superior pharmacoeconomic alternative compared with standard etoposide chemotherapy in managing SCLC. The potential increase in patient volume conferred by the relative simplicity of etoposide phosphate administration would have a significant impact on operations in terms of scheduling patients and staff and increasing operational efficiencies, thereby facilitating cost reductions in excess of $2,700 per patient when an etoposide phosphate regimen is chosen over an etoposide regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Plasma etoposide catechol increases in pediatric patients undergoing multiple-day chemotherapy with etoposide.

PURPOSE: The purpose of this research was to determine inter- and intrapatient differences in the pharmacokinetic profiles of etoposide and its genotoxic catechol metabolite during conventional multiple-day dosing of etoposide in pediatric patients. EXPERIMENTAL DESIGN: Seven pediatric patients with various malignancies received etoposide at a dose of 100 mg/m(2) i.v. over 1 h daily for 5 days. Blood samples were taken at selected time points on days 1 and 5. Plasma and protein-free plasma concentrations of etoposide and etoposide catechol were determined using a validated liquid chromatography/tandem mass spectrometry assay. Pharmacokinetic parameters of both etoposide and etoposide catechol were calculated using the WinSAAM modeling program developed at NIH. RESULTS: The mean maximum concentration (C(max)) for total (0.262 +/- 0.107 micro g/ml) and free catechol (0.0186 +/- 0.0082 micro g/ml) on day 5 were higher than the mean C(max) for total (0.114 +/- 0.028 micro g/ml) and free catechol (0.0120 +/- 0.0091 micro g/ml) on day 1. The mean area under the plasma concentration-time curve (AUC)(24h) for total (105.4 +/- 49.1 micro g.min/ml) and free catechol (4.89 +/- 2.23 micro g x min/ml) on day 5 were much greater (P < 0.05) than those for total (55.9 +/- 16.1 micro g x min/ml) and free catechol (3.04 +/- 1.04 micro g x min/ml) on day 1. In contrast, the AUC(24h) for etoposide was slightly lower on day 5 than on day 1. CONCLUSIONS: The C(max) and AUC(24h) for etoposide catechol were significantly higher on day 5 than on day 1. This suggests that metabolism of etoposide to its catechol metabolite increases in pediatric patients receiving multiple-day bolus etoposide infusions. These findings may be relevant to future reduction of the risk of leukemia as a treatment complication, because etoposide and etoposide catechol are both genotoxins.

Adolescent↗
PubMed1996

Bioequivalence assessment of etoposide phosphate and etoposide using pharmacodynamic and traditional pharmacokinetic parameters.

The bioequivalence of etoposide phosphate, a prodrug of etoposide, to etoposide was assessed in a randomized, crossover study in 29 patients with histologically established solid tumors that had failed conventional treatment. Cohorts of patients received one treatment course each of etoposide and etoposide phosphate which consisted of a 100 mg/m2 per day etoposide equivalent dose infused i.v. over 1 hr on a Day 1 to 5 schedule of treatment. The second course was administered 21 days later or on recovery of blood cell counts. Plasma and urine samples were collected over 24 hr on Day 1 of each course and assayed for etoposide content by a validated HPLC/UV method. Resulting data were subjected to noncompartmental pharmacokinetic analysis. Hematology profiles were obtained by collecting blood samples prior to the first course and twice a week after each course. The pharmacodynamics and pharmacokinetics of etoposide were virtually identical after the two treatments. The point estimates (90% confidence intervals) for nadir WBC, granulocytes, hemoglobin, and platelets expressed as % decrease from the baseline, and for the pharmacokinetic parameters, Cmax, and AUC0 infinity, after intravenous etoposide phosphate relative to etoposide were 100% (96%, 105%), 97% (91%, 103%), 95% (82%, 109%), 95% (84%, 106%), 107% (101%, 113%), and 113% (107%, 119%), respectively. Therefore, etoposide phosphate is bioequivalent to etoposide based on pharmacokinetic and pharmacodynamic assessments.

Adult↗
PubMed2001

Simultaneous quantification of etoposide and etoposide phosphate in human plasma by capillary electrophoresis using laser-induced native fluorescence detection.

A method using capillary electrophoresis with UV laser-induced native fluorescence detection was developed as a sensitive and selective assay for the simultaneous determination of etoposide and etoposide phosphate in human plasma. Laser-induced native fluorescence detection with a frequency-doubled argon ion laser at an excitation wavelength of 257 nm was used for the simultaneous assay of etoposide and etoposide phosphate in plasma to improve the sensitivity compared to that obtained with UV absorption. The detection system consists of an imaging spectrograph and an intensified CCD camera which views an illuminated 1.5-mm section of the capillary. This setup is able to record the whole emission spectra of the analytes to achieve additional wavelength-resolved electropherograms. In the concentration range of 200 microg/L-50 mg/L in plasma for etoposide and 100 microg/L-20 mg/L for etoposide phosphate, coefficients of correlation were better than 0.998. Within-day variation determined with three different concentrations showed accuracies ranging from 91.0 to 109.3% for etoposide and from 91.2 to 109.9% for etoposide phosphate (n = 6) with a precision of about 8%. Day-to-day variation presented accuracies ranging from 91.8 to 107.9% for etoposide and from 94.4 to 109.3% for etoposide phosphate with a relative standard deviation less than 6% (n = 5). To our knowledge, this is the first method for the simultaneous quantification of etoposide and etoposide phosphate in plasma samples.

Antineoplastic Agents↗
PubMed1997

Conversion of the prodrug etoposide phosphate to etoposide in gastric juice and bile.

Etoposide phosphate is a water-soluble prodrug of etoposide. It was expected that this prodrug could be used to overcome the solubility limitations and erratic bioavailability of oral etoposide. To investigate the possibility of prodrug conversion to etoposide within the gastrointestinal lumen, etoposide phosphate was dissolved in water and incubated with human gastric juice or human bile in vitro. Samples were collected during 150 min and analysed for etoposide concentration with high-performance liquid chromatography. Conversion of prodrug to etoposide during incubation with gastric juice was negligible. There was significant conversion during incubation with bile at pH 7-8. The percentage of prodrug converted to etoposide at pH 8 after 60 min was 78 +/- 18% (mean +/- S.D.) for a 0.1 mg ml-1 prodrug solution and 36 +/- 26% for 0.5 mg ml-1. At pH 7, after 60 min 22% of prodrug was converted to etoposide when incubated at 0.1 mg ml-1 and 10% at 0.5 mg ml-1. No conversion was found after inactivation of alkaline phosphate (AP) by overnight heating of bile at 65 degrees C or by the addition of disodium edetate to the bile. In conclusion, because of AP in bile, variable conversion of etoposide phosphate to etoposide can be expected within the intestinal lumen after oral administration. This could have important pharmacokinetic consequences.

Antineoplastic Agents, Phytogenic↗
PubMed1993

Prolonged administration of low-dose, infusional etoposide in patients with etoposide-sensitive neoplasms: a phase I/II study.

PURPOSE: This trial evaluated the activity and toxicity of a prolonged schedule of low-dose, daily infusional etoposide in patients with etoposide-sensitive neoplasms. PATIENTS AND METHODS: Fifteen patients (non-Hodgkin's lymphoma, n = 10; small-cell lung cancer, n = 3; germ cell neoplasm, n = 2) were treated. Ten had received etoposide previously. Etoposide 18 to 25 mg/m2/d was administered by continuous intravenous infusion for at least 21 days, or until either leukocyte count decreased to less than 2,000/microL, platelets decreased to less than 75,000/microL, or tumor progressed. Plasma etoposide levels were monitored during infusion. RESULTS: Duration of therapy ranged from 21 to 560 days; uninterrupted infusion ranged from 21 to 153 days. Seven patients (47%) had an objective tumor response (six partial, one complete), with a median duration of 7 months (range, 2 to 19). Myelosuppression limited the infusion; however, only four patients had grade 4 leukopenia, and most tolerated infusions with mild to moderate leukopenia. Nine patients required RBC transfusions. Only one patient developed severe thrombocytopenia. Alopecia was universal; however, other grade 3 or 4 nonhematologic toxicities were not encountered. The mean serum etoposide concentration was 0.7 +/- 0.42 microgram/mL. Only three patients had serum etoposide levels greater than 1 microgram/mL. CONCLUSION: Etoposide administered as a low-dose continuous infusion is active in etoposide-sensitive neoplasms. Myelosuppression is the major toxicity, but seems reduced when compared with other schedules. Tumor cytotoxicity was demonstrated with plasma levels ranging from 0.5 to 1.0 microgram/mL. Chronic low doses of etoposide may be superior to the standard dose and schedule and further study of this issue is warranted.

Adult↗
PubMed1991

[Preliminary report on the effect of etoposide or etoposide and CDDP on recurrent prostate cancer].

Eight patients with recurrent prostate cancer were treated with Etoposide and CDDP or Etoposide alone. Etoposide was administered at a dose of 20 approximately 50 mg/m2/day for 5 consecutive days and CDDP was administered at a dose of 30 approximately 50 mg/m2 on the first day. Treatment was repeated every 3 or 4 weeks. Patients who were treated with combination chemotherapy (Etoposide + CDDP) were those with no hematological abnormalities, no renal dysfunction and good performance status. Three patients were treated with Etoposide and CDDP and five were treated with Etoposide alone. Clinical evaluation was as follows: 3 patients (2 with Etoposide and CDDP, 1 with Etoposide alone) had PR (37.5%) and 5 patients had PD (62.5%). We obtained the impression that lesions of soft tissue metastasis responded well to this chemotherapy and that this combination chemotherapy was more effective than Etoposide alone. Major complications were myelosuppression, gastrointestinal upset and loss of hair. However, they were tolerable in patients with good performance status. This combination chemotherapy (Etoposide + CDDP) seems to be worth further clinical trials to patients who were tolerable.

Aged↗
PubMed2004

Treatment of acute leukemia with idarubicin, etoposide and cytarabine (IDEA). A randomized study of etoposide schedule.

BACKGROUND: The differences in toxicity of etoposide following continuous or bolus infusion are unknown. METHODS: We studied the schedule-dependent toxicity of high-dose etoposide when combined with high-dose cytarabine and idarubicin (IDEA) in 138 patients with acute leukemia. Four groups of patients were studied: group I, relapse; group II, secondary acute myeloid leukemia (AML); group III, de novo AML, age >60 years; and group IV, induction failure or blast crisis of myeloproliferative syndrome. Treatment for groups I-III was idarubicin 8 mg/m(2) per day days 1-3, cytarabine 2000 mg/m(2) once a day days 1-6, and etoposide 1600 mg/m(2) total dose. Group IV treatment differed by cytarabine given twice daily days 1-6. Patients were randomized to etoposide as a continuous infusion days 1-6 or as a bolus infusion over 10 h on day 7. RESULTS: Continuous infusion etoposide produced significantly more oral mucositis than bolus etoposide. In groups I-III, comparing continuous and bolus etoposide, there was a median of 3 vs 0 days of grade 2 or more oral mucositis (P<0.0001) and 13.5 vs 0 days of total parenteral nutrition (TPN) (P=0.0003). Group IV patients had a median 7 vs 0 days of grade 2 or more oral mucositis (P<0.01) and 21 vs 7 days of TPN (P<0.003), respectively. There were no differences in hematologic recovery, length of hospital stay, complete remission rate or overall survival between the two etoposide schedules. Of groups I-III patients, 51% achieved complete remission, and 11% died from treatment-related complications. CONCLUSION: The toxicity profile of high-dose etoposide is schedule-dependent with prolonged exposure producing significantly more non-hematologic toxicity.

Adolescent↗
PubMed2004

Particular cutaneous side effects with etoposide-containing courses: is VP16 or etoposide phosphate responsible?

PURPOSE: Etoposide is commercially available in France in two different pharmaceutical forms: VP16 and its phosphate ester (etoposide phosphate, EP). EP shows better chemical and physical properties, is said to be less toxic but is five times more expensive than VP16. Some criteria were defined for the use of each form in the Paediatric Oncohaematology Department in Hopital Sud in Rennes. As some particular cutaneous side effects were observed during treatment with etoposide-based course in this department, a retrospective study was initiated. The aims of this work were to determine the side effects (especially cutaneous toxicity), whether the pharmaceutical formulation of etoposide had any influence on the toxicity of the drug, and whether the observed side effects resulted from etoposide alone or from particular antineoplastic drug associations. METHODS: Five types of etoposide-containing protocols were chosen: NB 97 and NB 99 (neuroblastoma), FRALLE 93 (acute lymphoid leukaemia), LAME 91 (acute myeloid leukaemia), OS 94 (osteosarcoma), Ewing 97 and Euro-Ewing 99 (Ewing sarcoma). The medical files of 36 children (88 EP courses, 25 VP16 courses) included in these protocols were analysed on the basis that if a child showed a side effect during a course, the child had to have recovered from that side effect before the beginning of the next course. RESULTS: Apart from classical side effects (haematological and digestive toxicities etc.), two particular cutaneous side effects were observed: (1) palmar-plantar eruptions and nail inflammations, and (2) irritation of the anal area and anal fissures. Those side effects were observed with three of the studied protocols: NB 97, OS 94 and Ewing sarcoma treatments. CONCLUSIONS: No striking differences in toxicity appeared between the two etoposide formulations, but this retrospective study seemed to confirm the appearance of particular cutaneous and anal side effects especially with two associations: (1) etoposide-ifosfamide (OS 94 and Ewing 97), and (2) etoposide-ifosfamide-Adriamycin-vincristine (VIDE course of the Euro-Ewing 99 protocol).

Adolescent↗
PubMed1992

What is the optimal dose and duration of treatment with etoposide? II. Comparative pharmacokinetic study of three schedules: 1 x 100 mg, 2 x 50 mg, and 4 x 25 mg of oral etoposide daily for 21 days.

The large interpatient and intrapatient pharmacokinetic variability of oral etoposide is well known. We investigated whether dose fractionation would result in less variability. Fifteen patients (five in each etoposide schedule) were given either 100 mg once daily, 50 mg twice daily, or 25 mg four times daily for 21 days. On days 1, 8, and 15 blood samples were collected during 24 hours to measure plasma etoposide levels. Hematologic toxicity was determined by weekly leukocyte and platelet counts and expressed as the relative decrease in these parameters. Once-daily administration of etoposide 100 mg correlated with a significantly higher peak concentration than was observed with the other two schedules. The mean area under the concentration versus time curve (AUC) and mean time with a plasma etoposide concentration above 1 microgram/mL were similar with the three schedules. Peak plasma concentrations, AUCs, and times with plasma concentration above 1 micrograms/mL correlated significantly with the relative decrease in leukocyte but not platelet counts. Large interpatient and intrapatient variability of pharmacokinetic parameters was observed with all three schedules. These data do not support fractionating a daily 100-mg etoposide dose. Moreover, it does not appear useful to adjust oral etoposide doses based on pharmacokinetic data obtained once during a prolonged treatment period. Finally, adjusting oral etoposide doses based on hematologic toxicity seems advisable to decrease the interpatient variability of etoposide's pharmacokinetics.

Administration, Oral↗