Multi-drug chemotherapy for pancreatic cancer.

4267 Background: G-FLIP, a low dose, multi-drug regimen, produced an objective response and stable disease rate of (7+6/34) 38% and overall median survival (MST) of 10.3 additional mos on adding 80 mg/M of Irinotecan to a 'failed' q2 wk Gemzar-Fluorouracil-Cisplatin regimen (The Oncologist 6:488 2001).,Subsequently, G-FLIP was used for all non-adjuvant applications. Interim analysis found overall MST of 15-18 mos (Bruckner et al, ICACT 2001; 2003). In part, treatment after G-FLIP 'failure' substituted Taxotere (Xeloda) or Methotrexate for Irinotecan in multi-drug regimens with a 20% rate of objective response (Bruckner et al, ASCO, San Francisco, 2004.) Currently, all new patients (pts) were updated.,Overall MST for 102 intent-to-treat pts from diagnosis is 15.5 mos, and 28% at 2 yrs. Survival of these new pre-registered pts matches MST of ideally resected pts in the pre-G-FLIP period (Snady et al, Cancer, 2001), in spite of currently excluding the successfully resected and including therapy-resistant pts. The role of pt characteristics in this poor-risk group is now under study: 70 received G-FLIP as primary therapy, 23 had stage III cancer, 57 had CA 19-9 of greater than 1000, 16 required substantial narcotics, and 23 had failed resection of the tumor. Overall analysis included pts normally too sick to be eligible for registration or protocol trials. 37 of 57 (65%) pts with data had at least a 50% reduction in 19-9 levels, and only 3 (5%) increased 25% or more over 3 mos. Recently Avastin partnered with failed drugs has also produced major RECIST responses, mixed responses, and even clearing of intra-hepatic jaundice. Avastin experience is too early to contribute to overall survival.,Findings support testing of broad applications for drug additions to failed drugs. Experience demonstrates heterogeneity of drug response, and crossover response with clinical benefit. Pancreatic cancer is a promising subject for testing laboratory-directed development efforts. No significant financial relationships to disclose.