ABSTRACT
The phase III MPACT trial for metastatic pancreatic cancer (PC) showed improved overall survival (OS), progression free survival (PFS) and response rates (RRs) for first-line nab-paclitaxel (Abraxane) and gemcitabine (the AG combination) compared to gemcitabine monotherapy. The safety and efficacy of the AG combination has not been systematically studied as second-line therapy or beyond for metastatic PC. We conducted an IRB-approved retrospective analysis of all patients diagnosed between September 2010 and August 2014 with advanced refractory PC that received combination treatment with AG at our institution. Demographic and survival data were extracted from the registry. Patients received nab-paclitaxel 125 mg/m2 and gemcitabine 1,000 mg/m2 and on days 1, 8 and 15 of a 28-day cycle with subsequent dose modifications based on tolerance. Data on 59 patients was available; the median age was 61; 55% were male; 56% received AG as second line therapy and 44% received it as third-line or beyond. Five (10%) patients had a confirmed partial response (PR), 23 (47%) had stable disease (SD) and 21 (43%) had disease progression as their best response. Among the 31 (52%) patients who received prior gemcitabine, 18 (58%) had clinical benefit; 3 had a PR and 15 had SD. The median OS was 3.9 months and the median progression-free survival was 3 months. Toxicity was similar to what was reported in the MPACT trial. This retrospective analysis suggests that AG is active in PC patients previously treated with either fluoropyrimidine-based therapy or gemcitabine-based therapy with manageable toxicities.
ABSTRACT
BACKGROUND: The efficacy of FOLFIRINOX for metastatic pancreatic cancer has led to its use in patients with earlier stages of disease. This study retrospectively analyzed a cohort of patients with locally-advanced pancreatic cancer (LAPC) treated with FOLFIRINOX. METHODS: Between 2008 and 2013, 51 treatment-naïve patients with LAPC at a single institution received first-line FOLFIRINOX with neoadjuvant intent, at the full dose as described in the PRODIGE 4/ACCORD 11 study. Combined chemoradiation was administered for those who remained unresectable after maximum response to chemotherapy. The primary outcome measure was overall survival (OS), and secondary outcomes were progression-free survival (PFS) and margin-negative (R0) resection rate, and toxicity profile. RESULTS: A total of 429 cycles of FOLFIRINOX were given with a median of 8 cycles (range 2-29) per patient; 66% of cycles were full dose. After chemotherapy, 27 (53%) received chemoradiation. The median OS was 35.4 months (95% CI 25.8-45). Ten (4 borderline resectable and 6 unresectable) patients had successful R0 resections; those who had R0 resections had a significantly longer survival than those who did not (3-year OS rate 67% versus 21%, log rank p = 0.042). Increasing number of full-dose cycles was significantly associated with increased survival. The toxicity profile was similar to previous reports of this regimen. CONCLUSIONS: FOLFIRINOX is feasible as neoadjuvant therapy for LAPC. Although the R0 resection rate was only 20%, the median OS of almost 3 years appears promising. Dose intensity and duration were associated with increased survival in this study, arguing against dose attenuated versions of this regimen.
