Methods: Chemonaive mCRC patients were treated with OX, 130 mg/m2 day 1 plus XEL, 1625 mg/m2/day days 1 to 14; B 7.5 mg/kg day 1; E, orally days 2 to 18 at 100 mg (I dose level) and 150 mg (II level), every 3 weeks. Treatment was administered for a maximum of 9 cycles or until PD or unacceptable toxicity (UT). The maximum tolerated dose (MTD) was defined as the dose level immediately preceding that in which dose-limiting toxicity (DLT) has been identified. DLT was the dose causing UT (defined with conventional NCI criteria) in ‡2 patients within a 3-6 patients cohort during the first cycle. Pharmacodynamic studies were conducted to evaluate tissue and circulating biologic factors. Results: To date 9 patients were enrolled. During the first cycle of therapy, according to the phase I objective definition, DLT was recorded in 1 patient at dose level I (diarrhea G3) and 2 patients at dose level II (diarrhea G3-4). Therefore, dose level II was defined as the DLT and 3 additional patients were treated at I dose level and no further UT was experienced. Overall, 43 complete cycles were administered (median 3; range 1-12). Overall toxicity is reported in the following table. Tumor shrinkage (5 pts) or stabilization (1 pt) were observed in 6/8 patients evaluable for response assessment. Conclusion: Diarrhea was responsible of DLT at II dose level (E 150 mg). E 100 mg is the recommended dose to be combined with chemotherapy and B for the Phase II part of the study. Pharmacodynamic correlative studies are ongoing.
Phase I-II study of sequential combination of XELOX and bevacizumab plus erlotinib (XELOX-TARAV) in first line colorectal patients:Run in phase I part
PEPE, Stefano;
2008-01-01
Abstract
Methods: Chemonaive mCRC patients were treated with OX, 130 mg/m2 day 1 plus XEL, 1625 mg/m2/day days 1 to 14; B 7.5 mg/kg day 1; E, orally days 2 to 18 at 100 mg (I dose level) and 150 mg (II level), every 3 weeks. Treatment was administered for a maximum of 9 cycles or until PD or unacceptable toxicity (UT). The maximum tolerated dose (MTD) was defined as the dose level immediately preceding that in which dose-limiting toxicity (DLT) has been identified. DLT was the dose causing UT (defined with conventional NCI criteria) in ‡2 patients within a 3-6 patients cohort during the first cycle. Pharmacodynamic studies were conducted to evaluate tissue and circulating biologic factors. Results: To date 9 patients were enrolled. During the first cycle of therapy, according to the phase I objective definition, DLT was recorded in 1 patient at dose level I (diarrhea G3) and 2 patients at dose level II (diarrhea G3-4). Therefore, dose level II was defined as the DLT and 3 additional patients were treated at I dose level and no further UT was experienced. Overall, 43 complete cycles were administered (median 3; range 1-12). Overall toxicity is reported in the following table. Tumor shrinkage (5 pts) or stabilization (1 pt) were observed in 6/8 patients evaluable for response assessment. Conclusion: Diarrhea was responsible of DLT at II dose level (E 150 mg). E 100 mg is the recommended dose to be combined with chemotherapy and B for the Phase II part of the study. Pharmacodynamic correlative studies are ongoing.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
