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Phase I study of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours.

Chen X, Oza AM, Kusenda Z, Yi QL, Kochman D, Moore MJ, Davis AJ, Siu LL - Br. J. Cancer (2003)

Bottom Line: Pharmacokinetic parameters of epirubicin were not affected by the sequence of drug administration.However, the AUCs of irinotecan and its metabolites were increased significantly when irinotecan and epirubicin were administered concurrently.This combination regimen has promising broad antitumour activity, and will be further evaluated in phase II studies in multiple tumour types.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Canada M5G 2M9. eric.chen@uhn.on.ca

ABSTRACT
This phase I study was conducted to determine the recommended phase II doses, safety profile, and antitumour activity of a combination regimen of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours. Cisplatin and epirubicin were given at fixed doses of 50 and 60 mg m(-2), respectively. The irinotecan dose was escalated at 10 mg m(-2) increments from a starting dose level of 70 mg m(-2). Epirubicin, irinotecan, and their metabolites were measured with HPLC methods. In all, 35 patients received 141 courses of treatment. Irinotecan dose was escalated in seven cohorts up to 130 mg m(-2), and then finally de-escalated to 110 mg m(-2). The dose-limiting toxicity was neutropenic fever. Nonhaematologic toxicities included mild to moderate nausea/vomiting, diarrhoea and fatigue. Of 34 patients with evaluable disease, one patient had a complete response and nine patients had partial response, yielding an overall response rate of 29.4%. Pharmacokinetic parameters of epirubicin were not affected by the sequence of drug administration. However, the AUCs of irinotecan and its metabolites were increased significantly when irinotecan and epirubicin were administered concurrently. This combination regimen has promising broad antitumour activity, and will be further evaluated in phase II studies in multiple tumour types.

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Related in: MedlinePlus

Dose standardised mean plasma irinotecan concentrations in Course 1 (administered immediately after epirubicin) and Course 2 (administered 2 days before epirubicin).
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fig1: Dose standardised mean plasma irinotecan concentrations in Course 1 (administered immediately after epirubicin) and Course 2 (administered 2 days before epirubicin).

Mentions: Values are expressed as means ±s.d.


Phase I study of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours.

Chen X, Oza AM, Kusenda Z, Yi QL, Kochman D, Moore MJ, Davis AJ, Siu LL - Br. J. Cancer (2003)

Dose standardised mean plasma irinotecan concentrations in Course 1 (administered immediately after epirubicin) and Course 2 (administered 2 days before epirubicin).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376925&req=5

fig1: Dose standardised mean plasma irinotecan concentrations in Course 1 (administered immediately after epirubicin) and Course 2 (administered 2 days before epirubicin).
Mentions: Values are expressed as means ±s.d.

Bottom Line: Pharmacokinetic parameters of epirubicin were not affected by the sequence of drug administration.However, the AUCs of irinotecan and its metabolites were increased significantly when irinotecan and epirubicin were administered concurrently.This combination regimen has promising broad antitumour activity, and will be further evaluated in phase II studies in multiple tumour types.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Canada M5G 2M9. eric.chen@uhn.on.ca

ABSTRACT
This phase I study was conducted to determine the recommended phase II doses, safety profile, and antitumour activity of a combination regimen of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours. Cisplatin and epirubicin were given at fixed doses of 50 and 60 mg m(-2), respectively. The irinotecan dose was escalated at 10 mg m(-2) increments from a starting dose level of 70 mg m(-2). Epirubicin, irinotecan, and their metabolites were measured with HPLC methods. In all, 35 patients received 141 courses of treatment. Irinotecan dose was escalated in seven cohorts up to 130 mg m(-2), and then finally de-escalated to 110 mg m(-2). The dose-limiting toxicity was neutropenic fever. Nonhaematologic toxicities included mild to moderate nausea/vomiting, diarrhoea and fatigue. Of 34 patients with evaluable disease, one patient had a complete response and nine patients had partial response, yielding an overall response rate of 29.4%. Pharmacokinetic parameters of epirubicin were not affected by the sequence of drug administration. However, the AUCs of irinotecan and its metabolites were increased significantly when irinotecan and epirubicin were administered concurrently. This combination regimen has promising broad antitumour activity, and will be further evaluated in phase II studies in multiple tumour types.

Show MeSH
Related in: MedlinePlus