Reduction of the local toxicity of intraperitoneal chemotherapy; an experimental model

Abstract

Intraperitoneal (I.P.) administration of chemotherapeutic agents, in particular, cisplatin and bleomycin is successfully used in the treatment of ovarian and gastrointestinal malignancies. Their use however, is limited by the rapid development of adhesions. The vinca alkaloid group of chemotherapeutic agents has been shown to impair the acute inflammatory reaction, which plays an important role in adhesion formation, thereby providing the rationale for addition of vindesine to an I.P. regimen containing cisplatin and bleomycin. A rat model was used to study the effects of various I.P. chemotherapeutic regimens on adhesion formation. Four groups were studied (30 rats/Group). Regimens used included Group A (Saline), Group B (Vindesine 0.1 mg/kg), Group C (Cisplatin 5 mg/kg and Bleomycin 0.2 mg/kg), and Group D (Cisplatin 5 mg/kg, Bleomycin 0.2 mg/kg and Vindesine 0.1 mg/kg). In order to grade adhesion formation, animals were sacrificed on days 2, 14 and 28, with the severity of adhesions graded on a scale of I-IV in order of increasing severity. Adhesion formation in Group A (Saline) and Group B (Vindesine) was similar. The addition of Vindesine to Group C (Cisplatin and Bleomycin) resulted in a significant reduction in adhesion formation (p less than 0.01). The results of this experimental study suggest that the local toxicity of I.P. chemotherapy may be reduced by the inclusion of a vinca alkaloid.