The purpose of this study was to evaluate pharmacokinetic parameters, efficacy, and toxicity of a combination of docetaxel (DTX) and vinorelbine (VNB) in recurrent heavily pretreated squamous cell head and neck cancer. Twenty-nine patients previously treated with concomitant chemoradiotherapy (n = 14), surgery plus radiotherapy (n = 13), surgery + concomitant chemoradiotherapy (n = 1) and radiotherapy alone (n = 1) were enrolled; 9 patients had received I or more courses of palliative chemotherapy. Twenty-one patients had a local-regional recurrence, and 8 patients had metastases. The doses were 80 mg/m(2) for DTX and 20 mg/m(2) for VNB on day I every 21 days for a maximum of 6 cycles. Pharmacokinetic evaluations were performed on 24 patients; in a group of 12 patients, VNB; administration immediately followed DTX infusion (schedule A), and in 12 patients VNB administration was immediately followed by DTX infusion (schedule 13). Twenty-nine patients received a total of 137 cycles (median per patient, 5). Neutropenia was the most frequent and severe side effect (grade IV in 79%; grade III in 21%). Grade IV (7%) and III (14%) infections were observed in the first 12 patients; ciprofloxacin prophylaxis in the following 17 patients reduced the severe toxicity to 0%. The overall response rate was 49%, which included 3 of 29 complete responses (10%) and 11 of 29 partial responses (38%). Median complete and partial response durations were 20+ and 5.5 months, respectively. Overall median survival was 10 months (range, 2-30+). The mean values of area under the curve, mean residence time (MRT), and C-max of VNB, were significantly lower for schedule A than for schedule B. The mean values of VNB clearance were significantly higher for schedule A than for schedule B. Neutrophil count at the nadir was much lower for patients receiving schedule B. The DTX-VNB combination is effective in heavily pretreated patients with a short-lasting manageable toxicity. Pharmacokinetic evaluations suggested that the sequence DTX --> VNB is safer than the sequence VNB --> DTX.
Docetaxel and vinorelbine in recurrent head and neck cancer - pharmacokinetic and clinical results
CATTEL, Luigi;SUCCO, Giovanni;
2003-01-01
Abstract
The purpose of this study was to evaluate pharmacokinetic parameters, efficacy, and toxicity of a combination of docetaxel (DTX) and vinorelbine (VNB) in recurrent heavily pretreated squamous cell head and neck cancer. Twenty-nine patients previously treated with concomitant chemoradiotherapy (n = 14), surgery plus radiotherapy (n = 13), surgery + concomitant chemoradiotherapy (n = 1) and radiotherapy alone (n = 1) were enrolled; 9 patients had received I or more courses of palliative chemotherapy. Twenty-one patients had a local-regional recurrence, and 8 patients had metastases. The doses were 80 mg/m(2) for DTX and 20 mg/m(2) for VNB on day I every 21 days for a maximum of 6 cycles. Pharmacokinetic evaluations were performed on 24 patients; in a group of 12 patients, VNB; administration immediately followed DTX infusion (schedule A), and in 12 patients VNB administration was immediately followed by DTX infusion (schedule 13). Twenty-nine patients received a total of 137 cycles (median per patient, 5). Neutropenia was the most frequent and severe side effect (grade IV in 79%; grade III in 21%). Grade IV (7%) and III (14%) infections were observed in the first 12 patients; ciprofloxacin prophylaxis in the following 17 patients reduced the severe toxicity to 0%. The overall response rate was 49%, which included 3 of 29 complete responses (10%) and 11 of 29 partial responses (38%). Median complete and partial response durations were 20+ and 5.5 months, respectively. Overall median survival was 10 months (range, 2-30+). The mean values of area under the curve, mean residence time (MRT), and C-max of VNB, were significantly lower for schedule A than for schedule B. The mean values of VNB clearance were significantly higher for schedule A than for schedule B. Neutrophil count at the nadir was much lower for patients receiving schedule B. The DTX-VNB combination is effective in heavily pretreated patients with a short-lasting manageable toxicity. Pharmacokinetic evaluations suggested that the sequence DTX --> VNB is safer than the sequence VNB --> DTX.File | Dimensione | Formato | |
---|---|---|---|
Docetaxel 2003.pdf
Accesso riservato
Tipo di file:
POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione
235.91 kB
Formato
Adobe PDF
|
235.91 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.