Continuous infusion (CI) 5-FU and leucovorin (LCV) combined with hepatic (H), nodal (N), and tumor bed (TB) irradiation (XRT) following pancreaticoduodenectomy (PDD) for head of pancreas (HOP) and other periampullary (PA) adenocarcinoma

Purpose: To make preliminary assessment of whether use of this regimen in the post PDD adjuvant context is associated with: (1) an acceptable toxicity profile and (2) encouraging survival results as compared to either no or standard (GITSG) adjuvant (adj) therapy. Methods: From 10/1/91 through 9/30/95 28 post PDD patients (pts) (21 HOP, 7 PA) received adj chemoxrt with CI 5-FU (200 mg/m2) and LCV (5 mg/m2) via a semi-permanent central line Monday thru Friday along with H, N, and TB XRT. The first 18 pts received XRT doses of 2340 cGy (H) and 5040 cGy (N and TB). The last 10 pts received XRT doses of 2700 cGy (H), 5400 cGy (N), and 5760 cGy (TB). Fraction size = 180 cGy. XRT was administered after computerized and CAT scan based planning using 6 MV or greater photon energy. Therapy began within 10 wks of PDD. 1 month following chemoxrt, pts were to begin the first of 4 monthly cycles of 5-FU/LCV given without xrt but at the same doses and scheduled Monday thru Friday for 2 weeks on followed by 2 weeks off. Results: (M(F)) ratio (12(16)). The median age was 58 yrs (range 44-76). 23 pts had +ve nodes (10 pts had 5 or more +ve nodes). 6 pts had microscopically +ve resection margins of whom 5 also had +ve nodes. 26 pts completed chemoxrt as planned. 1 pt failed to complete chemoxrt due to the onset of immune thrombocytopenia. 1 pt completed after delay due to family death. 15 pts did not complete the planned 4 cycles of 5-FU/LCV (9-disease progression on therapy, 3-toxicity, 3-other). 9 pts had IV catheter problems. 7 pts had mild to moderate emotional depression while on therapy. Pts were monitored for wt loss, decline in performance status, liver, GI, heme, esophageal, oral mucosal and hand/foot toxicities. There were no grade (4(5)) toxicities. The only grade 3 toxicities were hepatic (3 pts) (elevations in AST, ALT, OR ALK PHOS without jaundice or hepatic failure). Median actuarial survival for these 28 pts was 15 months (20 pts deceased). For the 21 HOP pts median actuarial survival was 17 months (mo) which did not change when the pts with microscopically +ve margins were excluded. When compared to a contemporaneous cohort of 99 PDD pts operated for HOP at our hospital who received std GITSG adj therapy no improvement in median survival was noted (17 mo vs 21 mo respectively). However, median survival was improved in both treated groups as compared to 54 contemporaneous HOP pts who refused adj therapy (median survival 12.5 mo) (p=0.002). At the time of this analysis 23 study pts had failed with first sites of disease progression including Hepatic (11), peritoneal/mesentery (5), or nodal/TB (6). Conclusions: Although this therapy is substantially more complicated to administer than std adj therapy, the toxicities were manageable and nonlimiting. The activity of the therapy was disappointing as judged by a high rate of disease progression on therapy (32%), no evidence of improved survival, and no evidence of altered patterns of disease failure