HUMAN OVARIAN-CANCER XENOGRAFTS IN NUDE-MICE - CHEMOTHERAPY TRIALS WITH PACLITAXEL, CISPLATIN, VINORELBINE AND TITANOCENE DICHLORIDE

The new cytostatics titanocene dichloride and vinorelbine were compare d to cisplatin and paclitaxel using a human ovarian cancer xenografts model, Biopsy material from a native human ovarian carcinoma was expan ded and transplanted into 96 nude mice. The animals were divided into six treatment groups: cisplatin 3 x 4 mg/kg, paclitaxel 5 x 26 mg/kg, vinorelbine 1 x 20 mg/kg, titanocene dichloride 3 x 30 mg/kg, titanoce ne dichloride 3 x 40 mg/kg and a control group treated with 0.9% salin e. Each experiment was repeated with eight mice in each treatment grou p. Treatment groups were evaluated in terms of average daily increase in tumor volume and average daily body weight increase of nude mice ba sed on slopes of least-square regressions performed on individual anim als. The slope factors alpha and beta of the body weight (alpha) and t umor volume changes (beta) within each group during the course of an e xperiment were calculated. Both a statistically significant decrease ( p<0.05) in the body weight of the experimental animals (cisplatin: alp ha=-0.5163, vinorelbine: alpha=-0.6598, paclitaxel: alpha=-0.6746, tit anocene dichloride 3 x 30 mg/kg: alpha=-0.6259, titanocene dichloride 3 x 40 mg/kg: alpha=- 0.7758) and a significant reduction (p<0.05) of the increase in tumor volume (cisplatin: beta=12.049, vinorelbine: bet a=0.504, paclitaxel: beta=-1.636, titanocene dichloride 3 x 30 mg/kg: beta=6.212, titanocene dichloride 3 x 40 mg/kg: beta=-0.685) was shown in all treated groups compared to the control group (alpha=-0.1398; b eta=23.056). No significant weight changes were observed between the i ndividually treated groups. A statistically significant reduction of t he tumor growth occured under paclitaxel (beta=-1.636), vinorelbine (b eta=0.504) and titanocene dichloride medication 3 x 40 mg/kg (beta=-0. 685), as compared to the group treated with cisplatin (beta=12.049). W e found titanocene dichloride to be as effective as paclitaxel and mor e effective than cisplatin. Vinorelbine seems to he a very effective a ntineoplastic agent exhibiting a significant higher cytostatic effect than cisplatin. Both titanocene dichloride and vinorelbine provide new therapeutic options in women with ovarian carcinoma not responding to standard chemotherapy. [(C) 1998 Lippincott-Raven Publishers.].