Large volume loading to prevent cisplatin-induced nephrotoxicity during negative-balance isolated pelvic perfusion
Cisplatin, or cis-diamminedichloroplatinum(II) (CDDP), is an antineoplastic agent developed in 1965 by Rosenberg et al. , who were studying the effects of electrolysis products from a platinum electrode on growing cells. Cisplatin was clinically tested in 1972 by Hill et al. . In spite of its good antineoplastic activity against ovarian, lung, bladder, breast, head and neck.~ and testicular cancer, its clinical use was rapidly limited due to unexpected and very severe renal toxicity. Acute and cumulative renal toxicity associated with histological damage has been shown in both animal and human studies. Several theories concerning the pathophysiological mechanism behind this toxicity have been suggested [13, 59]. Since the therapeutic efficacy of cisplatin seems to be proportional to the delivered dose , there has been a continuous search for biological and pharmacological strategies to protect the renal function and thus permit the administration of high quantities of the drug; these strategies include modification of administration modes, development of new galenic forms, and the use of chemoprotectors, among others. Additionally, other platinum analogs with less nephrotoxicity have been studied, but these agents have less antitumor activity than cisplatin or have other inherent toxicities restricting their use .