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

TitlePhase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors
Authors
Issue Date2014
Citation
Invest New Drugs, 2014, v. 32 n. 4, p. 700-709 How to Cite?
AbstractPURPOSE: 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 TbetaRIII 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.
Persistent Identifierhttp://hdl.handle.net/10722/207682
ISSN
2015 Impact Factor: 3.281
2015 SCImago Journal Rankings: 1.376

 

DC FieldValueLanguage
dc.contributor.authorRangwala, Fen_US
dc.contributor.authorBendell, JCen_US
dc.contributor.authorKozloff, MFen_US
dc.contributor.authorArrowood, CCen_US
dc.contributor.authorDellinger, Aen_US
dc.contributor.authorMeadows, Jen_US
dc.contributor.authorTourt-Uhlig, Sen_US
dc.contributor.authorMurphy, Jen_US
dc.contributor.authorMeadows, KLen_US
dc.contributor.authorStarr, Aen_US
dc.contributor.authorBroderick, Sen_US
dc.contributor.authorBrady, JCen_US
dc.contributor.authorCushman, SMen_US
dc.contributor.authorMorse, MAen_US
dc.contributor.authorUronis, HEen_US
dc.contributor.authorHsu, SDen_US
dc.contributor.authorZafar, SYen_US
dc.contributor.authorWallace, Jen_US
dc.contributor.authorStarodub, ANen_US
dc.contributor.authorStrickler, JHen_US
dc.contributor.authorPang, HMHen_US
dc.contributor.authorNixon, ABen_US
dc.contributor.authorHurwitz, HIen_US
dc.date.accessioned2015-01-14T08:33:20Z-
dc.date.available2015-01-14T08:33:20Z-
dc.date.issued2014en_US
dc.identifier.citationInvest New Drugs, 2014, v. 32 n. 4, p. 700-709en_US
dc.identifier.issn0167-6997en_US
dc.identifier.urihttp://hdl.handle.net/10722/207682-
dc.description.abstractPURPOSE: 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 TbetaRIII 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.en_US
dc.languageengen_US
dc.relation.ispartofInvest New Drugsen_US
dc.titlePhase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumorsen_US
dc.typeArticleen_US
dc.identifier.emailPang, HMH: herbpang@hku.hken_US
dc.identifier.authorityPang, HMH=rp01857en_US
dc.identifier.doi10.1007/s10637-014-0089-2en_US
dc.identifier.volume32en_US
dc.identifier.issue4en_US
dc.identifier.spage700en_US
dc.identifier.epage709en_US

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