Phase II trial of neoadjuvant fixed dose rate (FDR) gemcitabine with capecitabine (GX) combination chemotherapy in locally advanced pancreatic adenocarcinoma (LAPA)

Abstract

e15553 Background: To determine the efficacy and safety of fixed dose rate (FDR) gemcitabine and capecitaibne (GX) combination chemotherapy for locally advanced pancreatic adenocarcinoma Methods: Patients with histologically confirmed LAPA were eligible for this prospective phase II trial. Dynamic pancreas/pelvic CT, MRI and FDG-PET were undertaken to assess the resectability. EUS was also performed as needed basis. ‘Borderline resectable (BR)’ and ‘unresectable (UR)’ criteria developed by our pancreatico-biliary multidisciplinary management team (PBMMT) and NCCN criteria were used. After confirmation of resectability, patients received 3 cycles of FDR gemcitabine 1,250 mg/m2 on D1 and D8 and capecitabine 950 mg/m2 from D1-D14 every 3 weeks. Thereafter, staging was repeated and patients underwent surgery if the disease was not unresectable. For patients with R0 resection, additional 6 cycles of GX were administered. For patients with R1 resection, chemoradiotherapy (CRT) (54 Gy over 5 weeks with concurrent 5-FU and leucovorin or capecitabine) followed by FDR-GX was administered. Patients with stable or better response to chemotherapy but assessed unresectable at reassessment received additional chemotherapy up to 9 cycles followed by CRT. Results: Between August 2006 and July 2008, 38 eligible patients (14 with BR and 24 with UR based on NCCN criteria; 29 with BR and 9 with UR based on our PBMMT criteria) entered on this study. The median age was 61 yo (42–76) and 71% had cT4 disease. The response to neoadjuvant chemotherapy was PR in 6 (16%), SD in 26 (68%) and PD in 3 (8%). Metabolic response was achieved in 20 patients (53%) with 2 metabolic CR out of 31 evaluable patients. Grade 3 or worse adverse effects were mainly HFS (n=5) and gastrointestinal (n=3) with no grade 4 in severity. Surgery was performed in 9 patients (24.0%, R0=8, R1=1, 6 in NCCN-BR and 3 in NCCN-UR, 9 in PBMMT-BR) and five patients refused surgery although their diseases seemed not to be unresectable. The median PFS was 9.4 months (95% CI, 8.3–10.4) and estimated median OS was 13.5 months (95% CI, 12.4- 14.5). Conclusions: FDR-GX was effective as neoadjuvnat chemotherapy in LAPA with favorable toxicity profile. No significant financial relationships to disclose.