Gemcitabine and nab-paclitaxel in patients with unresectable/borderline resectable pancreatic cancer.

Abstract

e14675 Background: Targeting the tumor stroma has evolved as a promising therapeutic strategy. Secreted protein acidic rich in cysteine (SPARC) which binds albumin has been putatively linked to enhanced drug delivery of nab-paclitaxel (ABX) to pancreatic tumor stroma. A recent phase I/II study demonstrated a 44% response in patients with metastatic pancreatic cancer treated with gemcitabine (gem) and ABX (Von Hoff et al, ASCO 2009). Based on these encouraging results, a pilot investigation was conducted in patients with unresectable (UR)/borderline resectable (BR) disease. Methods: A retrospective review was done on UR/BR pancreatic ca patients treated at Mayo Clinic Arizona from 3/09-12/09. Patients received gemcitabine 1,000 mg/m2 and nab-paclitaxel 100-125 mg/m2 neoadjuvantly. Demographics, staging, RECIST response, CA19-9 response (defined as > 50% maximal decline), EORTC PET response, post-treatment resectabilty and treatment related toxicities were assessed. Results: 13 patients were treated with this combination (age: median 69, range 47-86 years; sex: male 6, female 7, ECOG: 0-10, 1-3; location: head 8, body 5, median baseline CA19-9: 397 u/mL). A median of 3 cycles of therapy was delivered (range: 3-6). 3/13 (23%) underwent surgical resection with curative intent. CA19-9 response was 13/13 (100%), RECIST response was: PR-9/13 (69%), SD-3/13 (23%) and PD-1/13 (8%). EORTC PET response was: PR-7/10 (70%), SD3/10 (30%). No patients encountered drug related grade 4 or higher toxicities. There were 2 cases of grade 3 neutropenia,1 case of grade 3 anemia and no cases of grade 3 or higher thrombocytopenia; 4 patients had grade 2 neuropathy. Conclusions: Gemcitabine and nab-paclitaxel has a very promising antitumor activity in unresectable and borderline resectable pancreatic cancer patients. Investigation in a larger cohort of patients is ongoing. No significant financial relationships to disclose.