A Phase I Dose-Escalation Study of Imatinib Mesylate (Gleevec/STI571) plus Capecitabine (Xeloda) in Advanced Solid Tumors

作者:Dugan Elizabeth; Truax Roxanne; Meadows Kellen L; Nixon Andrew B; Petros William P; Favaro Justin; Fernando Nishan H; Morse Michael A; Blobe Gerard C; Hurwitz Herbert I*
来源:Anticancer Research, 2010, 30(4): 1251-1256.

摘要

The aim of this study was to determine the maximally tolerated dose, recommended phase II dose and toxicity profile of capecitabine plus imatinib mesylate combination. Patients and Methods: Twenty-four patients with advanced solid tumors were treated with capecitabine twice daily on days 1-14 and imatinib mesylate once daily on a 21-day cycle. Dose-limiting toxicity was assessed during the first cycle. Treatment continued until disease progression or undesirable toxicity. Results: Six patients were treated with capecitabine at 1000 mg/m(2) and imatinib mesylate 300 mg; unacceptable toxicity due to grade 2 intolerable hand-foot syndrome and/or grade >= 2 diarrhea was observed. Doses were subsequently reduced to capecitabine at 750 mg/m(2) and imatinib mesylate at 300 mg; toxicities were better tolerated at the lower dose. Dose-limiting toxicities consisted of grade 3 diarrhea, anorexia and fatigue lasting >= 4 days. Treatment-related adverse events greater than or equal to grade 3 included anemia, diarrhea, dysuria, hypophosphatemia and vertigo. Minor responses were observed in two patients: stable disease >= 6 months was observed in two out of twenty-one evaluable patients. Conclusion: Full doses of capecitabine and imatinib mesylate were not tolerable. The maximum tolerated dose and the recommended phase II dose for this drug combination is capecitabine at 750 mg/m(2) twice daily for 1-14 days and imatinib at 300 mg once daily on a 21-day cycle.

  • 出版日期2010-4