Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors.

Purpose: Diflomotecan (BN80915) is an E-ring modified camptothecin analogue that possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors, a potential advantage for antitumor activity. As with other camptothecins, oral administration has pharmacological and clinical advantages. This Phase I study was performed to assess the feasibility of the administration of oral diflomotecan, to determine the maximum-tolerated, dose its bioavailability, and to explore the pharmacokinetics.

Radiation-induced rectal complications are not influenced by age: a dose fractionation study in the rat.

Radiation-induced complications of the rectum are an important dose-limiting factor in radiotherapy of pelvic malignancies. In general, animal studies demonstrated no differences in acute and late normal tissue toxicity with age, but little is known about rectal complications in relation to age. For this purpose, an extensive histological and dose fractionation study was carried out on the rectum of young (12 weeks) and older (77-80 weeks) rats.

Effect of age on radiation-induced early changes of rat rectum. A histological time sequence.

Background And Purpose: Radiation treatment of the elderly (> 75 years) is often modified due to an assumed decrease in normal tissue tolerance in this age group. Since more radiobiological data concerning normal tissue toxicity as a function of age are needed, a histological study of age-related radiation changes of the rectum was performed.

Materials And Methods: The rectum of young and old female Wistar rats (12 and 78 weeks, respectively) was irradiated with single doses of 22 and 39 Gy.

Equivalence of hyperfractionated and continuous brachytherapy in a rat tumor model and remarkable effectiveness when preceded by external irradiation.

Purpose: In clinical brachytherapy, there is a tendency to replace continuous low-dose-rate (LDR) irradiation by either single-dose or fractionated high-dose-rate (HDR) irradiation. In this study, the equivalence of LDR treatments and fractionated HDR (2 fractions/day) or pulsed-dose-rate (PDR, 4 fractions/day) schedules in terms of tumor cure was investigated in an experimental tumor model.

Methods And Materials: Tumors (rat rhabdomyosarcoma R1M) were grown s.

Tumor hypoxia--a confounding or exploitable factor in interstitial brachytherapy? Effects of tissue trauma in an experimental rat tumor model.

Purpose: To evaluate the potential effects of tumor hypoxia induced by afterloading catheter implantation on the effectiveness of brachytherapy in a rat tumor model.

Methods And Materials: Afterloading catheters (4) were implanted in subcutaneously growing R1M rhabdomyosarcoma in female Wag/Rij rats. A MicroSelectron (Nucletron) was used for interstitial high-dose-rate irradiation ((192)Ir).

A 27 MHz current source interstitial hyperthermia system for small animals.

Temperature distribution is an important factor in thermo-radiotherapy and it is greatly dependent on the applied heating technique. Consistency of the heating method is therefore important in translating in vivo experimental data to the clinical situation. To further evaluate the combination of interstitial hyperthermia and interstitial radiotherapy, an experimental interstitial hyperthermia system has been developed for small (500-2000 mm3) tumours growing in the flank of a rat.

Interstitial hyperthermia and interstitial radiotherapy of a rat rhabdomyosarcoma; effects of sequential treatment and consequences for clonogenic repopulation.

Animal tumour experiments have been performed to elucidate the interactions between interstitial hyperthermia (IHT) and interstitial radiotherapy (IRT), and to obtain information about the most effective sequence of these treatment modalities. Experimental tumours, transplanted in the flank of Wag/Rij rats, were treated with IHT for 0.5 h at 44 degrees C, and with IRT using low dose-rate (LDR) iridium-192 sources.