title: The neuroprotective effect of erythropoietin in docetaxel-induced peripheral neuropathy causes no reduction of antitumor activity in 13762 adenocarcinoma-bearing rats.
abstract: Taxanes, including docetaxel (DOCE), are severely neurotoxic, causing disabling peripheral neuropathy. Co-treatment with neuroprotective agents has been proposed to prevent or reverse this. Besides its hemopoietic effects, erythropoietin (EPO) has neuroprotective and neurotrophic properties and when administered systemically it has a wide range of neuroprotective action in animal models of nervous system damage, including cisplatin-induced peripheral neurotoxicity. The present study investigated the effects of EPO on chemotherapy-induced peripheral neurotoxicity (CINP) by DOCE in vivo and whether it interfered with tumor growth or antitumor activity. Female Fischer rats bearing 13762 mammary carcinoma were randomly divided into four groups: untreated, treated with EPO, DOCE, or DOCE + EPO. DOCE was given once a week (5 mg/kg, i.v.) and EPO three times a week (50 microg/kg i.p.), for 4 weeks. Three other groups of rats without tumors were left untreated or given DOCE or DOCE + EPO. The rats were observed for 4 weeks after treatment. CINP and neuroprotection were evaluated by measuring nociception, electrophysiological, and biochemical parameters. EPO protected against CINP, and tumor growth in EPO-treated rats was the same as in controls. EPO significantly improved the thermal threshold, tail nerve conduction velocity, and intra-epidermal nerve fiber density. These benefits lasted through the follow-up period and EPO speeded-up spontaneous recovery after treatment withdrawal. EPO did not impair DOCE antitumor activity. Since CINP induced by DOCE reproduces the clinical utility of taxane in humans, the findings reported might provide a basis for investigating EPO as a neuroprotective agent in patients receiving therapy with DOCE.
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cervellini
authors.forename: Ezia
authors.initials: E
authors.lastname: Bello
authors.forename: Roberta
authors.initials: R
authors.lastname: Frapolli
authors.forename: Carla
authors.initials: C
authors.lastname: Porretta-Serapiglia
authors.forename: Norberto
authors.initials: N
authors.lastname: Oggioni
authors.forename: Annalisa
authors.initials: A
authors.lastname: Canta
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lombardi
authors.forename: Francesca
authors.initials: F
authors.lastname: Camozzi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Roglio
authors.forename: Roberto Cosimo
authors.initials: RC
authors.lastname: Melcangi
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'incalci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.forename: Pietro
authors.initials: P
authors.lastname: Ghezzi
authors.forename: Guido
authors.initials: G
authors.lastname: Cavaletti
authors.forename: Roberto
authors.initials: R
authors.lastname: Bianchi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077143:Docetaxel; D004347:Drug Interactions; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D043823:Taxoids / Q000009:adverse effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D043823:Taxoids; D004921:Erythropoietin; D000077143:Docetaxel