Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study

Andrew X. Zhu, Jeffrey A. Meyerhardt, Lawrence S. Blaszkowsky, Avinash R. Kambadakone, Alona Muzikansky, Hui Zheng, Jeffrey W. Clark, Thomas A. Abrams, Jennifer A. Chan, Peter C. Enzinger, Pankaj Bhargava, Eunice L. Kwak, Jill N. Allen, Sanjay R. Jain, Keith Stuart, Kerry Horgan, Susan Sheehan, Charles S. Fuchs, David P. Ryan, Dushyant V. Sahani

Research output: Contribution to journalArticle

Abstract

Background: Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose ([18F]FDG)-PET correlate with clinical outcome. Methods: Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m2 (10 mg/m2 per min) and oxaliplatin 85 mg/m2 (2-h infusion). [18F]FDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00361231. Findings: 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7·0 months (95% CI 5·3-10·3), and PFS at 6 months was 63% (47-79), which was below the targeted rate of 70%. Grade 3-4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). [18F]FDG-PET scans showed a significant decrease in maximum standardised uptake value (SUVmax) after two cycles of treatment (5·72 [SD 2·01] at baseline; 3·73 [SD 1·88] after two cycles; pmax was a significant predictor of PFS (HR 1·35, 1·14-1·60, p=0·0006) and overall survival (1·25, 1·05-1·50, p=0·01). Interpretation: GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUVmax on [18F]FDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival. Funding: Genentech Oncology and Sanofi-Aventis.

Original languageEnglish (US)
Pages (from-to)48-54
Number of pages7
JournalThe Lancet Oncology
Volume11
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

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oxaliplatin
gemcitabine
Biliary Tract Neoplasms
Disease-Free Survival
Safety
Positron-Emission Tomography
Intention to Treat Analysis
Survival
Poisons
Peripheral Nervous System Diseases
Patient Safety
Neutropenia
Alanine Transaminase
Therapeutics
Bevacizumab
Hypertension

ASJC Scopus subject areas

  • Oncology

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Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome : a phase 2 study. / Zhu, Andrew X.; Meyerhardt, Jeffrey A.; Blaszkowsky, Lawrence S.; Kambadakone, Avinash R.; Muzikansky, Alona; Zheng, Hui; Clark, Jeffrey W.; Abrams, Thomas A.; Chan, Jennifer A.; Enzinger, Peter C.; Bhargava, Pankaj; Kwak, Eunice L.; Allen, Jill N.; Jain, Sanjay R.; Stuart, Keith; Horgan, Kerry; Sheehan, Susan; Fuchs, Charles S.; Ryan, David P.; Sahani, Dushyant V.

In: The Lancet Oncology, Vol. 11, No. 1, 01.2010, p. 48-54.

Research output: Contribution to journalArticle

Zhu, AX, Meyerhardt, JA, Blaszkowsky, LS, Kambadakone, AR, Muzikansky, A, Zheng, H, Clark, JW, Abrams, TA, Chan, JA, Enzinger, PC, Bhargava, P, Kwak, EL, Allen, JN, Jain, SR, Stuart, K, Horgan, K, Sheehan, S, Fuchs, CS, Ryan, DP & Sahani, DV 2010, 'Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study', The Lancet Oncology, vol. 11, no. 1, pp. 48-54. https://doi.org/10.1016/S1470-2045(09)70333-X
Zhu, Andrew X. ; Meyerhardt, Jeffrey A. ; Blaszkowsky, Lawrence S. ; Kambadakone, Avinash R. ; Muzikansky, Alona ; Zheng, Hui ; Clark, Jeffrey W. ; Abrams, Thomas A. ; Chan, Jennifer A. ; Enzinger, Peter C. ; Bhargava, Pankaj ; Kwak, Eunice L. ; Allen, Jill N. ; Jain, Sanjay R. ; Stuart, Keith ; Horgan, Kerry ; Sheehan, Susan ; Fuchs, Charles S. ; Ryan, David P. ; Sahani, Dushyant V. / Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome : a phase 2 study. In: The Lancet Oncology. 2010 ; Vol. 11, No. 1. pp. 48-54.
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T1 - Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome

T2 - a phase 2 study

AU - Zhu, Andrew X.

AU - Meyerhardt, Jeffrey A.

AU - Blaszkowsky, Lawrence S.

AU - Kambadakone, Avinash R.

AU - Muzikansky, Alona

AU - Zheng, Hui

AU - Clark, Jeffrey W.

AU - Abrams, Thomas A.

AU - Chan, Jennifer A.

AU - Enzinger, Peter C.

AU - Bhargava, Pankaj

AU - Kwak, Eunice L.

AU - Allen, Jill N.

AU - Jain, Sanjay R.

AU - Stuart, Keith

AU - Horgan, Kerry

AU - Sheehan, Susan

AU - Fuchs, Charles S.

AU - Ryan, David P.

AU - Sahani, Dushyant V.

PY - 2010/1

Y1 - 2010/1

N2 - Background: Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose ([18F]FDG)-PET correlate with clinical outcome. Methods: Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m2 (10 mg/m2 per min) and oxaliplatin 85 mg/m2 (2-h infusion). [18F]FDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00361231. Findings: 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7·0 months (95% CI 5·3-10·3), and PFS at 6 months was 63% (47-79), which was below the targeted rate of 70%. Grade 3-4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). [18F]FDG-PET scans showed a significant decrease in maximum standardised uptake value (SUVmax) after two cycles of treatment (5·72 [SD 2·01] at baseline; 3·73 [SD 1·88] after two cycles; pmax was a significant predictor of PFS (HR 1·35, 1·14-1·60, p=0·0006) and overall survival (1·25, 1·05-1·50, p=0·01). Interpretation: GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUVmax on [18F]FDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival. Funding: Genentech Oncology and Sanofi-Aventis.

AB - Background: Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose ([18F]FDG)-PET correlate with clinical outcome. Methods: Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m2 (10 mg/m2 per min) and oxaliplatin 85 mg/m2 (2-h infusion). [18F]FDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00361231. Findings: 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7·0 months (95% CI 5·3-10·3), and PFS at 6 months was 63% (47-79), which was below the targeted rate of 70%. Grade 3-4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). [18F]FDG-PET scans showed a significant decrease in maximum standardised uptake value (SUVmax) after two cycles of treatment (5·72 [SD 2·01] at baseline; 3·73 [SD 1·88] after two cycles; pmax was a significant predictor of PFS (HR 1·35, 1·14-1·60, p=0·0006) and overall survival (1·25, 1·05-1·50, p=0·01). Interpretation: GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUVmax on [18F]FDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival. Funding: Genentech Oncology and Sanofi-Aventis.

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