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O Soepenberg

Publications and source records attributed to O Soepenberg.

7 recordsLinked to original sources
PubMed2004

Real-time pharmacokinetics guiding clinical decisions; phase I study of a weekly schedule of liposome encapsulated paclitaxel in patients with solid tumours.

The purpose of this weekly schedule phase I study of liposome encapsulated paclitaxel (LEP) was to define the maximum-tolerated dose (MTD), the recommended dose (RD), the dose-limiting toxicities (DLTs), the pharmacokinetic profiles, and to evaluate preliminarily antitumour effects in patients with refractory solid malignancies. LEP was administered as an intravenous (i.v.) infusion over 45 min once every week for 6 out of 8 weeks. Fourteen patients were treated at doses ranging from 90 to 150 mg/m(2)/week. In one patient, DLT was observed at the dose level of 150 mg/m(2)/week, who received less than 70% of the intended cumulative dose. No cumulative toxicities were observed. Stabilisation of disease for 8 weeks was documented in two patients. The whole blood clearance of total paclitaxel was similar for LEP (15.3+/-8.98 l/h/m(2)) and Taxol (17.5+/-3.43 l/h/m(2)), and the extraliposomal to total drug ratio increased rapidly to unity at later sampling time points. The trial was discontinued upon completion of enrolment of the 150 mg/m(2)/week cohort because an assessment of the pharmacokinetics and clinical data suggested that LEP was unlikely to have any advantages over Taxol. It is concluded that this formulation of LEP is unlikely to provide improvements over the taxanes currently in clinical use.

Adult↗
PubMed2003

Influence of the cisplatin hydration schedule on topotecan pharmacokinetics.

The study described here was designed to investigate the influence of the hydration schedule of cisplatin on the pharmacokinetics of topotecan. To test this hypothesis, 13 adult cancer patients were treated with intravenous (i.v.) cisplatin followed by i.v. topotecan for 5 days every 3 weeks using a short hydration schedule (SHS) for cisplatin in the first course and a hyper-hydration schedule (HHS) in the second course or vice versa. Topotecan pharmacokinetic analysis was performed in plasma, whole blood and red blood cells in both courses on days 1, 2 and 5. 11 patients received both courses and were pharmacokinetically evaluable. No significant differences between the two studied schedules were noted in the clearances of topotecan on day 1 in the different matrices. However, in both hydration schedules, on average, slightly lower topotecan clearances were observed on both days 2 and 5 compared with day 1 in all of the matrices, while no differences were noted between days 2 and 5. This alteration was independent of the schedule used and was less pronounced than that which has been initially reported for SHS and, overall, will not have clinical consequences.

Adult↗
PubMed2001

Modulation of camptothecin analogs in the treatment of cancer: a review.

The topoisomerase I inhibitors reviewed in this paper are all semisynthetic analogs of camptothecin (CPT). Modulation of this intranuclear enzyme translates clinically in to antitumor activity against a broad spectrum of tumors and is therefore the subject of numerous investigations. We present preclinical and clinical data on CPT analogs that are already being used in clinical practice [i.e. topotecan and irinotecan (CPT-11)] or are currently in clinical development (e.g. 9-aminocamptothecin, 9-nitrocamptotecin, lurtotecan, DX 8951f and BN 80915), as well as drugs that are still only developed in a preclinical setting (silatecans, polymer-bound derivates). A variety of different strategies is being used to modulate the systemic delivery of this class of agents, frequently in order to increase antitumor activity and/or reduce experienced side effects. Three principal approaches are discussed, including: (i) pharmaceutical modulation of formulation vehicles, structural alterations and the search for more water-soluble prodrugs, (ii) modulation of routes of administration and considerations on infusion duration, and (iii) both pharmacodynamic and pharmacokinetic biomodulation.

Animals↗
PubMed1994

Phase I/II study of intraperitoneal mitoxantrone in refractory ovarian cancer.

BACKGROUND: Mitoxantrone has demonstrable clinical activity when administered intravenously in a wide range of malignancies. The feasibility and toxicity of intra-peritoneal administration was established in a phase I study. The optimal dose from the phase I was subsequently evaluated in a phase II study. PATIENTS AND METHODS: 19 patients with refractory malignancies and extensive abdominal disease (13 ovarian cancer, 4 breast cancer, 2 mesothelioma) were entered in a phase I study. The dose of intraperitoneal mitoxantrone was escalated from 10 mg/m2, administered in 21 of fluid via a Tenckhoff catheter, to 55 mg/m2, in increments of 5 mg/m2. Cycles were repeated every three weeks. Sixty-seven cycles of mitoxantrone were administered, the maximum tolerable dose being 25 mg/m2. A phase II study at this dose was conducted in 14 patients with refractory ovarian cancer, all of whom had previously received systemic platinum based therapy. Five of the 14 had also previously been treated with intraperitoneal carboplatin. Fifty-one cycles were administered. RESULTS: The dose limiting toxicity in the phase I study was peritoneal irritation and pain. Leucopenia was frequent at doses equal or greater than 30 mg/m2. Three complete remissions were documented in the phase I study (2 breast cancer and 1 ovarian cancer). There was no significant haematological toxicity in the phase II assessment, though local toxicity precluded further therapy in 2 patients. No objective responses were seen in the phase II evaluation. CONCLUSIONS: These studies demonstrate the feasibility of intra-peritoneal mitoxantrone therapy in patients with peritoneal disease, but do not support its routine use in ovarian cancer.

Abdominal Pain↗