Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.

Journal Article (Clinical Trial;Journal Article;Multicenter Study)

PURPOSE: To define maximum tolerated dose (MTD), toxicities, and pharmacodynamics of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumor patients. DESIGN: This was a standard "3 + 3" dose-escalation trial. All subjects received bevacizumab 7.5 mg/kg on day 1 of each cycle. Doses for capecitabine, oxaliplatin and everolimus were modified per dose limiting toxicity (DLT). Baseline and on-treatment plasma biomarkers were analyzed. Archived tumor mRNA levels were evaluated for NRP1, NRP2 and VEGF-A isoforms. RESULTS: Twenty-nine patients were evaluable for toxicity and 30 for efficacy. Two DLTs were observed in cohort 1 and one DLT each was observed in cohort -1 and -1b. Grade ≥3 toxicities included neutropenia, hypertension, perforation/fistula/hemorrhage, hypertriglyceridemia, diarrhea, and thromboembolism. Twelve subjects experienced partial response (PR); 12 had stable disease as best response. Three of seven chemorefractory metastatic colorectal cancer (mCRC) subjects experienced PR; 8 of 15 chemonaive mCRC subjects experienced PR. Plasma TβRIII and IL-6 increased on treatment but without correlation to outcome. Increased VEGF165 levels significantly correlated with longer progression free survival. CONCLUSIONS: Everolimus with full dose capecitabine, oxaliplatin, and bevacizumab had unacceptable toxicity. MTD was: everolimus 5 mg daily; capecitabine 680 mg/m(2) BID days 1-14; oxaliplatin 100 mg/m(2) and bevacizumab 7.5 mg/kg, day 1. Activity was noted in mCRC.

Full Text

Duke Authors

Cited Authors

  • Rangwala, F; Bendell, JC; Kozloff, MF; Arrowood, CC; Dellinger, A; Meadows, J; Tourt-Uhlig, S; Murphy, J; Meadows, KL; Starr, A; Broderick, S; Brady, JC; Cushman, SM; Morse, MA; Uronis, HE; Hsu, SD; Zafar, SY; Wallace, J; Starodub, AN; Strickler, JH; Pang, H; Nixon, AB; Hurwitz, HI

Published Date

  • August 2014

Published In

Volume / Issue

  • 32 / 4

Start / End Page

  • 700 - 709

PubMed ID

  • 24711126

Pubmed Central ID

  • PMC4103954

Electronic International Standard Serial Number (EISSN)

  • 1573-0646

Digital Object Identifier (DOI)

  • 10.1007/s10637-014-0089-2


  • eng

Conference Location

  • United States