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
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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