A preliminary pharmacokinetic study of docetaxel, carboplatin and concurrent radiotherapy for regionally advanced squamous cell carcinoma of the head and neck.
This work investigates the pharmacokinetics and toxicity resulting from the concomitant use of low dose carboplatin (CBCA)/docetaxel (DTX) plus concurrent radiotherapy in patients with head and neck cancer. The study comprised 11 patients with stage III-IV head and neck cancer. All patients received 2 Gy radiotherapy daily, 5 fractions per week, up to a planned total of 70 Gy over 7 weeks. CBCA (AUC 0.4 mg/ml, min/day) was also administrated as 20 min i.v. infusion, starting 1 day before the first radiotherapy fraction. CBCA was administered for 5 consecutive days every 2 weeks (weeks 1, 3, 5 and 7). DTX 30 mg/m2 (1 h i.v. infusion) was given as a single dose on days 10, 24 and 38. CBCA on day 1 and DTX on day 10 were analysed to determine the concentration-time curves during the first 24 h. CBCA Cmax and Cmin in 2-5 days and on day 15 and 29, as well as total plasma platinum on days 2, 3, 4, 5, 29 and 43 were also assayed. By calculating the non-compartmental pharmacokinetic parameters of the two drugs from the available plasma concentrations we found in the first week values similar to those reported in the literature as single agents. In contrast, during subsequent weeks (weeks 3 and 5), a significant and progressive increase of platinum levels was observed. So, it could be assumed that after 2 weeks of CBCA and DTX treatment a bias in dose calculation occurred because the linear relationship between creatinine clearance (used to calculate the expected AUC through the Calvert formula) and CBCA clearance was no longer observed.
Cattel
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L
Dipartimento di Scienza e Tecnologia del Farmaco, Scuola di Specializzazione in Farmacia Ospedaliera, Turin, Italy. cattel@pharm.unito.it
Recalenda
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Airoldi
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Tagini
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Delprino
L
L
Rocco
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Bumma
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D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D016190:Carboplatin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D002851:Chromatography, High Pressure Liquid; D003131:Combined Modality Therapy; D000077143:Docetaxel; D006207:Half-Life; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D007262:Infusions, Intravenous; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D043823:Taxoids
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017239:Paclitaxel