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A Phase I Study, with Expanded Cohort, of Biweekly Fixed-Dose Rate Gemcitabine (FDR GEM) Plus Capecitabine (CAP) in Patients with Advanced Pancreatic (APC) and Biliary Carcinomas (ABC)

Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr 4136)

Author(s): A. M. Espinoza, A. H. Ko, A. P. Venook, E. K. Bergsland, K. A. Jones, R. K. Kelley, W. M. Korn, E. Dito, A. Ong, M. A. Tempero; University of California, San Francisco, San Francisco, CA; University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

Abstract:

Background: GEM-based therapy remains the standard of care for APC and ABC. The addition of CAP to GEM has produced modest improvements in clinical outcomes compared to GEM alone in several phase III studies in APC. This NCCN-supported study seeks to optimize dosing, schedule, and administration of these drugs by using an alternating-week dose schedule of FDR GEM plus CAP.

Methods: Patients (pts) with previously untreated APC/ABC and ECOG PS 0-1 were eligible. A standard 3+3 dose-escalation schema was used (see Table). First- degree objective: establishment of maximum tolerated dose (MTD); second degree: TTP, OS, radiographic, and CA 19-9 response, and safety.

Results: A total of 42 pts (median age 61 yrs; 93% APC/7% ABC; 83% with metastatic dz) have been enrolled. MTD was established at dose level +1; however, due to late toxicity at this dose level (notably gr 2/3 hand-foot syndrome [HFS]), maximum recommended dose (MRD) is dose level 0, at which further cohort expansion took place. Most frequent non-heme AEs: N/V (overall 67%; all gr 1/2), HFS (overall 57%; gr 3/4, 19%), fatigue (overall 55%; gr 3/4 2%), diarrhea (overall 31%; gr 3/4, 2%), and lab abnormalities (overall 45%; gr 3/4 10%). Gr 3/4 hematologic toxicity was observed in 24% of pts (5% neutropenic fever). 43% of pts required dose reduction of one or both drugs, but only 29% at MRD. Of 37 pts eligible for efficacy analysis, 8 (22%) have had unconfirmed PR and 18 (49%) SD for at least 4 cycles, for an overall dz control rate of 71% (median number of cycles received = 10). 18 of 28 pts (64%) with elev baseline CA 19-9 level had >50% decline during rx. Estimated TTP and OS were 5.5 and 9.7 mo, respectively. Specific to the metastatic pancreatic CA cohort (n=32), est. TTP and OS were 6.2 and 10.4 mo, with a 1-yr survival rate of 29%.

Conclusions: The MRD for this dosing schedule is FDR GEM 1,000 mg/m2 on day 1 plus CAP 1,000 mg/m2 bid on days 1-7, every 14 days. Preliminary data suggest this alternating-week regimen to be active and well tolerated in pts with APC/ABC. Results from completed accrual (n=44) will be presented at the Meeting

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