Investigation of bioavailability and pharmacokinetics of treosulfan capsules in patients with relapsed ovarian cancer

Hilger, Ralf A.; G, Jacek; Oberhoff, C.; Kredtke, S; Baumgart, Joachim; Seeber, S.; Scheulen, M. E.

doi:10.1007/s002800051023

Cited by 22 publications

(22 citation statements)

References 18 publications

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“…[3][4][5]7,8 Total systemic clearance of treosulfan was in the wide range from 60 to 385 ml/min with a mean value of 232 ml/min after a dose of 12 g/m 2 , similar to the value of 225 ml/min of adult patients treated the same dose 7 or a different dose (1.0-1.5, 8.0, 10.0 or 14.0 g/m 2 ). 3,4,7 The small value of 60 ml/min can be the result of reduced creatinine clearance observed in the patient. The volume of distribution with a mean value about 25 l is also comparable with the data from the literature (19.5-34.0 l).…”

Section: Discussionmentioning

confidence: 50%

“…8 The biological half-life of terminal phase in paediatric patients was in the range of 1.71-2.15 h (Table 1), which is in good agreement with the previously published clinical reports, however, regarding adults. 3,4,7,8 Fraction of parent compound eliminated with urine was about 30% (range 21-45%) in the group of children treated with 12.0 g/m 2 during the first 12 h, of which 95% eliminated up to 6 h after treosulfan administration. In individual patients treated with 10.0 or 14.0 g/m 2 dose, the eliminated percentage of the drug was 16 and 26%.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Treosulfan has a broad spectrum of antitumour activity and it is registered for the treatment of ovarian carcinoma. [3][4][5][6] In addition, it was demonstrated both in vivo and in vitro that treosulfan reveals an excellent toxicity against all stem cell lines of the BM and this caused that it was recently administered in high doses within the conditioning regimen prior to allogeneic haematopoietic SCT in patients with haematological malignancies. 7 Despite the clinical use of the oral and i.v.…”

Section: Introductionmentioning

confidence: 99%

“…formulation, pharmacokinetic data for adult patients are rather scarce. [3][4][5]7,8 Treosulfan represents linear increase of area under the concentration (AUC) up to 56 g/m 2 in adult patients, whereas other pharmacokinetic parameters, such as halflife, volume of distribution and renal elimination, were independent of dose. 8 According to growing clinical experience, the high-dose treosulfan demonstrates low organ toxicity in paediatric patients when used as a part of the preparative regimen for haematopoietic SCT, 9,10 but until now there were no studies of the pharmacokinetics of the drug in children.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of high-dose i.v. treosulfan in children undergoing treosulfan-based preparative regimen for allogeneic haematopoietic SCT

Główka

Karaźniewicz−Łada

Grund

et al. 2008

Bone Marrow Transplant

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Pharmacokinetic studies of high-dose treosulfan were carried out in seven paediatric patients (age range: 2-15 years) undergoing treosulfan-based conditioning regimen prior to allogeneic haematopoietic SCT. Treosulfan was administered intravenously in a daily dose of 10, 12 or 14 g/m 2 within 2 h. Five out of seven patients received 12 g/m 2 . The plasma concentrations of treosulfan and its quantity eliminated with urine were determined using a validated HPLC method with refractometric detection. Pharmacokinetic parameters were evaluated following first dose using a two-compartment disposition model. These studies demonstrated a dose-dependent increase of area under the concentration (AUC) and maximum concentrationplasma (C max ), but there was variability of these parameters. Rapid clearance of tresoulfan was observed, especially in 10 and 12 g/m 2 doses. Terminal half-life (t 0.5 ) of treosulfan was in the range of 1.71-2.15 h, but the mean percent of parent drug eliminated with urine was 30%, range 16.3-45.4% of the total dose eliminated during the first 12 h after administration. The results of this study confirmed the linear pharmacokinetics of treosulfan, as used in children. However, variability of pharmacokinetic results observed in children studied demonstrates the need for pharmacokinetic evaluation in each paediatric patient undergoing the treosulfan-based preparative regimen, including those using different doses. This approach could enable further reduction of the risk of early and late organ toxicity related to high-dose treosulfan in paediatric patients.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetics of high-dose i.v. treosulfan in children undergoing treosulfan-based preparative regimen for allogeneic haematopoietic SCT

Główka

Karaźniewicz−Łada

Grund

et al. 2008

Bone Marrow Transplant

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“…Det er viktig å avgjøre om tablettkurer kan erstatte intravenøs behandling (21)(22)(23)(24)(25)(26).…”

Section: Problemstillingerunclassified

Tilbakefall av eggstokkreft og borderline tumorer i eggstokkene i Norge

Paulsen¹

2009

Nor J Epidemiol

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ENGLISH SUMMARYPaulsen T. Recurrence of ovarian cancer and borderline ovarian tumours in Norway.Nor J Epidemiol 2001; 11 (2): 143-146. Background:The 5-year relative survival for patients with ovarian cancer in Norway has improved over time, but is still less than 40%. Early diagnosis and optimal therapy can hopefully better the prognosis. In order to improve the techniques of examination, treatment and follow-up of these patients, the establishment of a system for quality insurance of clinical data for cancer in Norway (NOU 20, 1997) has been suggested. According to the answers of a questionnaire that was sent to the gynaecological departments in Norway in the spring of 2000, there were differences in how hospitals handle ovarian cancer patients. Introduction: The age-standardised incidence rate for ovarian cancer has increased from 11.9 per 100 000 person-years in 1957 to 13.3 per 100 000 in 1997. The incidences in the Nordic countries, with the exception of Finland, are among the highest in the world. The borderline ovarian tumours (BOT) had an incidence rate of 4.8 per 100 000 in the period 1970 to 1993. Aim:The main aim of this extended registration of ovarian cancer and BOT in Norway is to better document diagnostic procedures and treatment. We will emphasise the recurrence of ovarian cancer and BOT.Controversies: Only a few prospective protocols have been planned or carried out internationally that were randomised for different treatments of recurrent ovarian cancer. The studies that have been carried out have included only a few patients. In our project we will collect clinical information from the whole population of women with ovarian cancer and BOT in Norway. Surgery of women with recurrence of ovarian cancer in order to achieve tumour reduction is still controversial. Some authors claim that tumour reduction surgery improves the survival of these patients, but this is not proven. Some authors indicate that elderly patients may receive less surgical and chemotherapeutic treatment without obvious clinical rationale. Today we do not know which treatment of recurrence of ovarian cancer gives the longest survival and best quality of life. The incorporation of paclitaxel into first-line therapy improves the duration of progression-free survival and overall survival in women with incompletely-resected stage III and stage IV ovarian cancer. However we do not know which treatment gives the best overall survival in the case of recurrence. BOT are different from the invasive tumours of the ovary, with longer relative 5-year survival. BOT stage I has relative 5-year survival of 99% and for the advanced stages 92%. Probably BOT develop through accumulation of different genetic mutations than invasive epithelial ovarian tumours. Material and method: All women with diagnosed ovarian/tube/perinoneal cancer and BOT as primary disease or recurrence in Norway will be included in this study. About 500 women are diagnosed with ovarian cancer annually and 330 women with recurrence. The number of BOT is approximately 130 p...

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Treosulfan in the Treatment of Metastatic Melanoma: From Chemosensitivity Testing to Clinical Trials

Neuber¹

2003

Chemosensitivity Testing in Oncology

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Investigation of bioavailability and pharmacokinetics of treosulfan capsules in patients with relapsed ovarian cancer

Cited by 22 publications

References 18 publications

Pharmacokinetics of high-dose i.v. treosulfan in children undergoing treosulfan-based preparative regimen for allogeneic haematopoietic SCT

Pharmacokinetics of high-dose i.v. treosulfan in children undergoing treosulfan-based preparative regimen for allogeneic haematopoietic SCT

Tilbakefall av eggstokkreft og borderline tumorer i eggstokkene i Norge

Treosulfan in the Treatment of Metastatic Melanoma: From Chemosensitivity Testing to Clinical Trials

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