Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2

Abstract

Purpose Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS. Patients and Methods In the phase I part of this study, patients were randomly assigned to one of the following four parallel GA treatment arms (six patients per arm): a biweekly schedule of NAB-paclitaxel (150 mg/m2 [arm A] or 125 mg/m2 [arm C]) plus gemcitabine 1,000 mg/m2 or a standard schedule of 3 weeks on and 1 week off of NAB-paclitaxel (100 mg/m2 [arm B] or 125 mg/m2 [arm D]) plus gemcitabine 1,000 mg/m2. The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study, the primary end point of which was 6-month actuarial survival. Results Arms B and D were selected for the phase II part of the study. A total of 221 patients (111 patients in arm B and 110 patients in arm D) were enrolled. Baseline characteristics including median age (71 and 68 years in arms B and D, respectively), sex (51% and 55% men in arms B and D, respectively), and metastatic disease (88% and 84% in arms B and D, respectively) were comparable between arms. The most frequent grade 3 or 4 toxicities in arms B and D were anemia (12% and 7%, respectively), neutropenia (32% and 30%, respectively), thrombocytopenia (7% and 11%, respectively), asthenia (14% and 16%, respectively), and neurotoxicity (11% and 16%, respectively). In arms B and D, there were no significant differences in response rate (24% and 28%, respectively), median progression-free survival (5.7 and 6.7 months, respectively), and 6-month overall survival (63% and 69%, respectively). Conclusion NAB-paclitaxel administered at either 100 and 125 mg/m2 in combination with gemcitabine on days 1, 8, and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS.

A Review on Curability of Cancers: More Efforts for Novel Therapeutic Options Are Needed

“…For instance, approximately 90% of metastatic NSCLC and pancreatic cancer patients progressed within 15 months after chemotherapy, with 90% of metastatic gastric and advanced esophagogastric cancer progressing within 24 months [115,116,117,118]. The contribution of chemotherapy to the survival of advanced hepatocellular carcinoma and pancreatic cancer is marginal [115,119]. Escalated chemotherapy is not necessarily associated with improved survival.…”

<p>Enhancement of Antitumor Efficacy of Paclitaxel-Loaded PEGylated Liposomes by N,N-Dimethyl Tertiary Amino Moiety in Pancreatic Cancer</p>

“…Pancreatic cancer remains one of the most lethal cancers and it is currently highlighted by its resistance to chemotherapeutic drugs, which can be attributed in part to the dense stroma that acts as a physiological barrier of the tumor tissue. 39,40 Currently, albumin-bound PTX (nab-PTX) has been widely utilized in a large number of clinical trials [41][42][43][44][45] in combination with gemcitabine considering its relatively high concentration of PTX by targeting the PDAC stroma and its synergistic antitumor efficacy with gemcitabine. Thus, an appropriate nano delivery system with efficient stroma-penetrating ability through the PDAC barrier is a promising direction for further studies.…”

Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial–Mesenchymal Transition: Enhanced Efficacy when Combined with Gemcitabine

“…Efficacy and safety are critical considerations in the evaluation of anticancer agents [27,28]. Under the conditions tested, EGCG appears to satisfy these two critical requisites: Improved safety and enhanced efficacy.…”