Long-term pharmacokinetics of doxorubicin HCl stealth liposomes in patients after polychemotherapy with vinorelbine, cyclophosphamide and prednisone (CCVP)

The concentration-time profiles of Doxorubicin (DOXO) from day 0 to day 21 after Lv. infusion of 25 or 30 mg/m(2) doxorubicin HCl stealth liposomes (C aelyx (R)) were investigated in 9 patients receiving combination polychemot herapy with cyclophosphamide, vinorelbine and prednisone. Peak serum concen trations occurred from 0.04 to 4.0 days after infusion (mean t(max) = 1.79 +/- 1.55 d) with a mean c(max) of 4595 +/- 2849 ng/ml. A total amount of 12 .84 +/- 2.47 mg liposomal DOXO in the plasma volume (Vp = 2794 + 537 ml) co uld be estimated at t(max) (= 27% of the mean dose of 47.6 mg). Stealth lip osomes were eliminated slowly from the blood with a mean t(1/2)el of 1.9 0.5 days (MRT was 4.6 + 2.5 days). AUC(last) values ranged from 8070 to 33446 ng/ml*d (mean 10987 + 9339 ng/ml *d). The low plasma clearance (Cl-tot = 4681 +/- 2835 ml/day) and the small volume of distribution (Vz = 11.7 +/- 6.31) suggested that stealth-liposom es were stable in the blood at least for 14 days. Polychemotherapy with Hyp er-CCVP schedule did not alter the stability of stealth liposomes, but peak levels of DOXO seemed to be somewhat lower compared to regression analysis of literature data (c(max) versus dosage range from 20 to 60 mg/m(2)). Due to c(last) occurring between day 12 to 18, no indices for an accumulation of the drug in the blood could be found, when liposomes were given every fo ur weeks.