title: Hydration regimen and hematological toxicity of a cisplatin-based chemotherapy regimen. Clinical observations and pharmacokinetic analysis.
abstract: The administration of 100 mg/m2 Cisplatin (CDDP) in five 20 mg/m2 daily infusions together with bolus 5-Fluorouracil (5FU) allows patients with advanced head and neck cancer (HNC) to be treated with a rapidly alternating chemoradiotherapy regimen in an out-patient setting. Due to the extremely low rate of acute renal failure, the induction of forced diuresis is not mandatory, although hydration is usually performed at every CDDP administration. In this retrospective analysis of 73 homogenously treated HNC patients, the influence of hydration on hematological toxicity was studied. A lower incidence of grade II to IV acute myelosuppression (57% vs 92%; p < 0.005), together with a lower rate of anemia lasting two weeks or more (13% vs 46%; p < 0.009), were seen in the group of patients treated with CDDP along with a forced hydration scheme (2000 ml normal saline and 20 mg furosemide before the CDDP infusion) when compared to patients on a non-forced diuresis regimen (no furosemide and 1500 ml normal saline). The lower hematological toxicity translated into a better compliance to treatment. No differences in terms of other toxicities or response rate were evident between the two groups. A pharmacokinetic study with a cross over design was performed on 7 patients, and suggests that the first day Pt kinetics are not affected by the hydration scheme used, although a significantly lower Pt urinary concentration was found in the forced diuresis group. A further kinetic analysis performed on one additional patient over the entire five-day period of two consecutive cycles showed a marked increase in the AUC of filterable Pt and in the unbound Pt fraction (fu) from the second to the fifth day in the forced hydration course, while this was not the case in the non-forced hydration course. Results from this kinetic study support the hypothesis of a lowering of Pt reactive species after repeated CDDP-furosemide treatments and an influence of furosemide-induced diuresis on Pt binding to plasma proteins.
authors.affiliation: Divisione di Oncologia Medica I, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Numico
authors.forename: M
authors.initials: M
authors.lastname: Benasso
authors.forename: M O
authors.initials: MO
authors.lastname: Vannozzi
authors.forename: M
authors.initials: M
authors.lastname: Merlano
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: M
authors.initials: M
authors.lastname: Viale
authors.forename: M
authors.initials: M
authors.lastname: Esposito
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004231:Diuresis; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005665:Furosemide / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D007674:Kidney Diseases / Q000517:prevention & control; D007970:Leukopenia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000139:chemically induced*
chemical_list: D005665:Furosemide; D002945:Cisplatin; D005472:Fluorouracil