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 language | English (US) |
|---|---|
| Pages (from-to) | 48-54 |
| Number of pages | 7 |
| Journal | The Lancet Oncology |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=73249128451&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73249128451&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(09)70333-X
DO - 10.1016/S1470-2045(09)70333-X
M3 - Article
C2 - 19932054
AN - SCOPUS:73249128451
VL - 11
SP - 48
EP - 54
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 1
ER -