Pharmacokinetics of paclitaxel administered in combination with cisplatin,etoposide and bleomycin in patients with advanced solid tumours

Purpose: To evaluate the pharmacokinetics of paclitaxel and cisplatin admin istered in combination with bleomycin and etoposide and Granulocyte Colony- Stimulating Factor (G-CSF) in patients with advanced solid tumours. Methods : Patients were recruited to a phase I trial where escalating doses of pacl itaxel (125 to 200 mg/m(2)) were administered in combination with etoposide 100 or 120 mg/m(2), and fixed dose of cisplatin 20 mg/m(2) and bleomycin 3 0 mg, with the concomitant use of G-CSF. Paclitaxel (3-12 infusion) was fol lowed by 1-h etoposide, 4-h cisplatin and 30-min bleomycin infusions, respe ctively. Pharmacokinetics sampling for paclitaxel analysis was performed in ten patients from dose levels II-V. Results: The mean paclitaxel area unde r the plasma concentration-versus-time curves (AUC) for the 125-mg/m(2) dos e level (II) was 7.0 +/- 3.6 h mu mol(-1) l(-1) for the 175-mg/m(2) dose le vel (III) 10.6 +/- 2.8 h mu mol(-1) l(-1), for the 200-mg/m(2) dose level ( IV) it was 16.0 +/- 5.0 h mu mol(-1) l(-1), and for the 175-mg/m(2) dose le vel (V) it was 12.5 +/- 6.1 h mu mol(-1) l(-1). The mean peak plasma concen tration (C-max) values for dose levels II-V were 1.9 +/- 1.1 mu mol/l, 3.4 +/- 1.2 mu mol/l, 4.3 +/- 1.0 mu mol/l and 3.8 +/- 1.2 h mu mol/l, respecti vely. Conclusion: In this study, relevant pharmacokinetic parameters of pac litaxel like AUC, C-max and the paclitaxel plasma concentration above the p harmacologically relevant 0.1-mu mol/l threshold concentration (t > 0.1 mu M) when administered in combination with cisplatin, etoposide and bleomycin (PEB) were not statistically different from paclitaxel data of historical controls. However, given the trial design, pharmacokinetic interactions bet ween the agents cannot be excluded.