NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice

Ferdinando De Vita, Jole Ventriglia, Antonio Febbraro, Maria Maddalena Laterza, Alessio Fabozzi, Beatrice Savastano, Angelica Petrillo, Anna Diana, Guido Giordano, Teresa Troiani, Giovanni Conzo, Gennaro Galizia, Fortunato Ciardiello, Michele Orditura

Pancreatic adenocarcinoma is an aggressive disease with poor prognosis. In a randomized phase III trial, combination of Nab-paclitaxel (Nab-P) plus gemcitabine showed superior activity and efficacy in first-line treatment compared with gemcitabine alone. Nab-P is not dispensed in Italy; however, we obtained this drug from our Ethics Committee for compassionate use. The aim of this study was to evaluate the efficacy and safety profile of this Nab-P and gemcitabine combination in a cohort of patients treated outside clinical trials. From January 2012 to May 2014, we included 41 patients with advanced pancreatic adenocarcinoma receiving combination of 125 mg/m(2) Nab-P and 1 g/m(2) gemcitabine on days 1, 8 and 15 of a 28-day cycle, as first-line treatment. Median age of patients was 67 (range 41-77) years, and 11 patients were aged ≥70 years. Eastern Co-operative Oncology Group performance status was 0 or 1 in 32 patients (78 %) and 2 in nine patients (22 %). Primary tumor was located in the pancreatic head or body/tail in 24 (58.5 %) and 17 (41.5 %) patients, respectively, and nine patients had received biliary stent implantation before starting chemotherapy. Median carbohydrate antigen 19-9 level was 469 U/l (range 17.4-61546 U/l) and 29 patients (70.7 %) had referred pain at the time of diagnosis. Patients received a median six cycles (range 1-14) of treatment. Overall response rate was 36.6 %; median progression-free survival was 6.7 months [(95 % confidence interval (CI) 5.966-8.034), and median overall survival was 10 months (95 % CI 7.864-12.136). Treatment was well tolerated. No grade 4 toxicity was reported. Grade 3 toxicity included neutropenia in 10 patients (24.3 %), thrombocytopenia in five (12 %), anemia in three (7.3 %), diarrhea in four (9.7 %), nausea and vomiting in two (4.9 %), and fatigue in six (14.6 %). Finally, pain control was achieved in 24 of 29 patients (82.3 %) with a performance status improvement of 10 % according to the Karnofsky scale. Our results confirm that combination of gemcitabine plus Nab-P is effective both in terms of overall response rate, progression-free survival and overall survival, with a good safety profile.