BACKGROUND: To establish the recommended dose level (RDL) and to evaluate the efficacy and safety of gefitinib plus irinotecan in patients with advanced fluoropyrimidine-refractory colorectal cancer (CRC). PATIENTS AND METHODS: Patients with advanced CRC progressing on or within 12 weeks of fluoropyrimidine-based chemotherapy, irinotecan naive and performance status of two or less were recruited. During dose-finding phase, dose-limiting toxicity (DLT) was encountered at dose level 1, therefore subsequent dose de-escalation and pharmacokinetic (PK) studies were carried out. The RDL was then expanded in a multicentre setting to further evaluate safety and efficacy. RESULTS: From June 2002 to February 2005, 39 patients were treated in total with 27 at the RDL. The RDL was established at irinotecan 225 mg/m(2) every 3 weeks and gefitinib 250 mg daily. The DLTs were neutropenia and diarrhoea. For the patients treated at RDL, the objective tumour response rate was 11.1% (95% confidence interval 2.4% to 29.2%) and median survival was 9.3 months. PK studies indicated that the addition of irinotecan to gefitinib resulted in an average of 50% increase in exposure to gefitinib (P < 0.05), but gefitinib did not alter the PK profiles of irinotecan or SN-38. Grade 3-4 toxic effects in all patients included diarrhoea (35.9%), lethargy (15.4%), neutropenia (15.4%), febrile neutropenia (10.3%) and skin rash (7.7%). CONCLUSIONS: Irinotecan and gefitinib at this dose schedule was tolerable, but gefitinib did not appear to add substantial efficacy to irinotecan.
BACKGROUND: To establish the recommended dose level (RDL) and to evaluate the efficacy and safety of gefitinib plus irinotecan in patients with advanced fluoropyrimidine-refractory colorectal cancer (CRC). PATIENTS AND METHODS: Patients with advanced CRC progressing on or within 12 weeks of fluoropyrimidine-based chemotherapy, irinotecan naive and performance status of two or less were recruited. During dose-finding phase, dose-limiting toxicity (DLT) was encountered at dose level 1, therefore subsequent dose de-escalation and pharmacokinetic (PK) studies were carried out. The RDL was then expanded in a multicentre setting to further evaluate safety and efficacy. RESULTS: From June 2002 to February 2005, 39 patients were treated in total with 27 at the RDL. The RDL was established at irinotecan 225 mg/m(2) every 3 weeks and gefitinib 250 mg daily. The DLTs were neutropenia and diarrhoea. For the patients treated at RDL, the objective tumour response rate was 11.1% (95% confidence interval 2.4% to 29.2%) and median survival was 9.3 months. PK studies indicated that the addition of irinotecan to gefitinib resulted in an average of 50% increase in exposure to gefitinib (P < 0.05), but gefitinib did not alter the PK profiles of irinotecan or SN-38. Grade 3-4 toxic effects in all patients included diarrhoea (35.9%), lethargy (15.4%), neutropenia (15.4%), febrile neutropenia (10.3%) and skin rash (7.7%). CONCLUSIONS:Irinotecan and gefitinib at this dose schedule was tolerable, but gefitinib did not appear to add substantial efficacy to irinotecan.
Authors: José María Viéitez; Manuel Valladares; Ignacio Peláez; Luis de Sande González; Jesús García-Foncillas; José Luis García-López; Carlos García-Girón; Margarita Reboredo; Humberto Bovio; Angel Jiménez Lacave Journal: Invest New Drugs Date: 2010-03-06 Impact factor: 3.850
Authors: Wayne L Furman; Lisa M McGregor; M Beth McCarville; Mihaela Onciu; Andrew M Davidoff; Sandy Kovach; Dana Hawkins; Valerie McPherson; Peter J Houghton; Catherine A Billups; Jianrong Wu; Clinton F Stewart; Victor M Santana Journal: Invest New Drugs Date: 2011-07-28 Impact factor: 3.850
Authors: M Ponz-Sarvisé; J Rodríguez; A Viudez; A Chopitea; A Calvo; J García-Foncillas; I Gil-Bazo Journal: World J Gastroenterol Date: 2007-11-28 Impact factor: 5.742