title: An analysis of potential factors allowing an individual prediction of cisplatin-induced anaemia.
abstract: Severe cisplatin (CP)-induced anaemia significantly impairs the patient's quality of life. Prevention based on erythropoietin (EPO) administration would be cost-effective providing that individual predictive factors of anaemia are identified. The aim of the present study was to identify parameters able to predict the occurrence of CP-related anaemia. This prospective study was conducted on 40 head and neck cancer patients receiving a CP (100 mg/m(2), intravenous (i. v.) on day 1) - 5-fluorouracil (5-FU, 1 g/m(2)/dx5 days by continuous infusion) induction chemotherapy. Three cycles were given at 3-weekly intervals. Platinum pharmacokinetics (total and ultrafilterable plasma platinum concentration measured 16 h after CP administration) and 5-FU pharmacokinetics (full-cycle plasma area under the curve, (AUC(0-105h)30 g/l) occurred in 15 patients (38%) and 3 of them also received a blood transfusion. Patient age, 5-FU AUC(0-105h) and total platinum concentration were unrelated to Hb loss. In contrast, ultrafilterable (UF) platinum concentration was significantly correlated to Hb loss: the higher the UF platinum concentration, the greater the Hb loss (P=0.015). A discriminant analysis allowed a cut-off value for UF platinum to be proposed to identify patients developing significant loss of Hb: 91% of patients exhibiting a UF platinum concentration above 50 ng/ml developed significant loss of Hb in contrast to 18% in the group of patients with a UF platinum concentration below 50 ng/ml (odds ratio (95% confidence interval, CI) of 46 (4.7-446)). In conclusion, the present platinum pharmacokinetic survey may be proposed as a valuable approach to identify patients at risk for developing severe anaemia.
authors.affiliation: Centre Antoine Lacassagne, Oncopharmacology Unit, 33, avenue de Valombrose, 06189, Nice, France.
authors.forename: X
authors.initials: X
authors.lastname: Pivot
authors.forename: E
authors.initials: E
authors.lastname: Guardiola
authors.forename: M
authors.initials: M
authors.lastname: Etienne
authors.forename: A
authors.initials: A
authors.lastname: Thyss
authors.forename: C
authors.initials: C
authors.lastname: Foa
authors.forename: J
authors.initials: J
authors.lastname: Otto
authors.forename: M
authors.initials: M
authors.lastname: Schneider
authors.forename: N
authors.initials: N
authors.lastname: Magné
authors.forename: R J
authors.initials: RJ
authors.lastname: Bensadoun
authors.forename: N
authors.initials: N
authors.lastname: Renée
authors.forename: G
authors.initials: G
authors.lastname: Milano
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000175:diagnosis*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D002945:Cisplatin / Q000009:adverse effects* / Q000493:pharmacokinetics; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011788:Quality of Life
chemical_list: D000970:Antineoplastic Agents; D004921:Erythropoietin; D002945:Cisplatin