Phase II study of induction therapy with gemcitabine and nab-paclitaxel followed by consolidation with mFOLFIRINOX in patients with metastatic pancreatic cancer.

Authors

null

Ramesh K. Ramanathan

Translational Genomics Research Institute - Virginia G Piper Cancer Center, Scottsdale, AZ

Ramesh K. Ramanathan , Peter Lee , John E. Seng , Stephen Patrick Anthony , Peter J. Rosen , Raul R. Mena , Vincent J. Picozzi , Jasgit C. Sachdev , Tim Larson , Ronald Korn , Gayle S. Jameson , Amy C. Stoll , Daniel D. Von Hoff , Joseph W. Leach

Organizations

Translational Genomics Research Institute - Virginia G Piper Cancer Center, Scottsdale, AZ, Tower Cancer Research Foundation, Beverly Hills, CA, Minnesota Oncology, Minneapolis, MN, Evergreen Hematology and Oncology/US Oncology Research Affliate, Spokane, WA, Providence Saint Joseph Medical Center, Burbank, CA, Virginia Mason Medical Center, Seattle, WA, Imaging Endpoints, Scottsdale, AZ, Virginia G. Piper Cancer Center/Scottsdale Healthcare, Scottsdale, AZ, Translational Drug Development, Scottsdale, AZ

Research Funding

Other Foundation

Background: FOLFIRINOX or NabP-Gem are now standard mPC regimens.The optimal sequence is not known.This phase II study evaluated the feasibility of NabP-Gem followed by FOLFIRINOX. Methods: Eligible pts had evidence of untreated mPC, ECOG 0-1 and adequate organ function. Pts received Nab-P (125 mg/m2) and Gem (1000 mg/ m2) weekly x 3 (Induction ) every 4 weeks for upto 6 cycles. FOLFIRINOX, q2 weeks (Consolidation regimen) was initiated after 6 cycles of the Induction regimen, or earlier in case of progression, and given for a maximum of 6 months (12 cycles). mFOLFIRINOX (NEJM, 364:1817-25: 2011) has been modified with growth factor prophylaxis and omission of bolus 5FU. One endpoint is to increase 1 year survival to > 70%, (n=30, 95% CI is +/- 20%). Results: Accrual goals have been met (n=31). The M/F ratio is 55%/45%, median is 66 years. In 23 pts with elevated baseline CA19-9 levels treated with NabP-Gem, 83% had a > 90% decrease. The response rate with the NabP-Gem regimen is 43%. Selected therapy related Grade > 3 adverse events during the course of both NabP-Gem and FOLFIRINOX therapy are: neutropenia (39%), fatigue (32%), anemia (19%), thrombocytopenia (16%), thromboembolic events (3%), peripheral neuropathy (16%), leukopenia (16%), nausea (3%), vomiting (3%), diarrhea (7%), and neutropenic fever (3%). During the course of NabP-Gem, 14 dose reductions and four dose delays were seen. Two pts had early progression at cycle 4 or less and were switched to the Consolidation regimen. Seventy one % (22/31) of pts went on to receive FOLFIRINOX (4 pts still on study), 4 received FOLFIRI, and one pt received FOLFOX as Consolidation therapy. One-year survival is projected to be 50-60%. Conclusions: The induction NabP-Gem regimen shows evidence of substantial activity similar to published reports (JCO.29:4548-54: 2011). The induction-consolidation strategy is feasible in selected patients. Cumulative side effects predominantly fatigue and neuropathy will require appropriate dose reductions or treatment breaks. (Supported by the Seena Magowitz foundation). Clinical trial information: NCT01488552.

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Abstract Details

Meeting

2014 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

General Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Track

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Sub Track

Translational Research

Clinical Trial Registration Number

NCT01488552

Citation

J Clin Oncol 32, 2014 (suppl 3; abstr 224)

DOI

10.1200/jco.2014.32.3_suppl.224

Abstract #

224

Poster Bd #

A53

Abstract Disclosures