[Effects of adjuvant hyaluronidase in tumors refractory to chemotherapy. Review of the literature and pharmacokinetics of cisplatin after regional administration in animals and humans]

Abstract

Several clinical studies have recently suggested that topical or systemic adjuvant hyaluronidase may increase the therapeutic index of anticancer drugs. In cases of disease progression, further objective responses have been observed after the association of hyaluronidase to the previously employed drugs. Some evidences suggest that hyaluronidase improves local diffusion as well as tissue and tumor uptake of the associated drugs. Hence, plasma and tissue concentrations of platinum following administration of cisplatin alone and associated with hyaluronidase have been investigated in 20 rats after intraperitoneal injection and in 10 patients with colorectal liver metastases and local progression of the disease after regional and systemic chemotherapy with intraarterial cisplatin and intravenous 5-fluorouracil. Three out of six refractory patients treated with hepatic intraarterial cisplatin + hyaluronidase showed one minor response and two stable diseases, respectively, without any apparent increase of treatment related toxicity. In turn, adjuvant hyaluronidase increased both the extent distribution and lasting time of cisplatin in the body and reduced plasma levels of total and free platinum originating from cisplatin, without any modification of either unbound fraction of platinum or total body clearance. Hence, adjuvant hyaluronidase seems to increase tissue extraction of cisplatin and, particularly, liver extraction after intraarterial administration in man. These results encourage further studies aimed to determine the clinical role of adjuvant hyaluronidase in patients refractory to regional chemotherapy.