Age affects pegylated liposomal doxorubicin elimination and tolerability in patients over 70 years old.
OBJECTIVE
Pegylated liposomal doxorubicin (PLD) is often used in elderly people, due to its improved tolerability. However, clinical and pharmacological data in the subset of patients over 70 are scanty.


METHODS
PLD safety was evaluated in 35 patients (aged ≥70 years) who were treated with PLD as a single agent for 165 cycles. Doxorubicin plasma levels, leukocyte DNA breaks and monocyte count variations were measured as markers of drug exposure, DNA repair capability and reticuloendothelial system activation, respectively. A correlation between these markers and age was sought.


RESULTS
Treatment was generally well tolerated. Skin erythrodysesthesia was the most frequent side effect, and no severe (G4) toxicity occurred. PLD plasma half-life generally correlated with age (P < 0.001) and was particularly prolonged in octogenarians (P = 0.005). Doxorubicin clearance significantly declined up to 70 % at cycle 7. DNA breaks increased over the first two cycles (P = 0.007) and were inversely correlated with age (P = 0.007) and directly with clearance (P = 0.006). Pre-treatment monocyte counts increased over cycles (P < 0.001) and were associated with an increase in clearance at cycle 3 (P = 0.015). The hand-foot-skin syndrome was significantly more severe in patients of advanced age or longer PLD half-life.


CONCLUSIONS
This study showed (1) increased systemic drug exposure over subsequent cycles; (2) association of age with increased drug exposure, reduced DNA repair capability and worse skin toxicity; (3) a relation between monocyte count and drug clearance.
Department of Oncology, ULSS 18-Rovigo, S Maria della Misericordia Hospital, Rovigo General Hospital, Viale Tre Martiri 140, 45100, Rovigo, Italy, milenagusella@libero.it.
Milena
M
Gusella
Antonio
A
Bononi
Yasmina
Y
Modena
Laura
L
Bertolaso
Paola
P
Franceschetti
Daniela
D
Menon
Elisa
E
Pezzolo
Carmen
C
Barile
Giorgio
G
Crepaldi
Caterina
C
Bolzonella
Alessandro
A
Inno
Roberto
R
Padrini
Felice
F
Pasini
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin