A randomized phase II trial of gemcitabine, nab‐paclitaxel, cisplatin with or without a medically supervised ketogenic diet for patients with metastatic pancreatic cancer
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: ABSTRACT Background A randomized phase II screening trial of gemcitabine, nab‐paclitaxel, and cisplatin with a medically supervised ketogenic diet (MSKD) versus usual diet (non‐MSKD) was conducted in patients with treatment‐naive metastatic pancreatic ductal adenocarcinoma (PDAC). Methods Patients with untreated metastatic PDAC were randomized 1:1 to MSKD or non‐MSKD while receiving gemcitabine, nab‐paclitaxel, and cisplatin on days 1 and 8 of a 21‐day cycle. The MSKD was guided by a remote health care team and daily ketone (beta‐hydroxybutyrate) levels, with goal beta‐hydroxybutyrate of 0.5 to 3.0 mM. The primary endpoint was progression‐free survival (PFS) using a one‐sided alpha level of 0.20. Secondary endpoints included overall survival (OS), safety, and quality of life (QOL). Changes in microbiome were an exploratory endpoint. Findings Overall, there were 32 evaluable patients. In the MSKD arm, 15 of 16 patients achieved nutritional ketosis; the median proportion of days in ketosis was 39.4%. The median PFS was 8.5 months in MSKD patients and 6.2 months in non‐MSKD patients: hazard ratio, 0.53 (95% CI, 0.21–1.37); one‐sided p = .096. The median OS was 13.7 months with MSKD and 10.2 months in the non‐MSKD arm: hazard ratio, 0.58 (95% CI, 0.25–1.37); one‐sided p = .107). All MSKD‐related adverse events were grade 1‐2. There were no significant differences in grade ≥3 chemotherapy‐related adverse events between the arms. MSKD patients had no decline in QOL and had significant enrichment of beneficial taxa in the microbiome ( p < .05, log‐fold change ≥2). Conclusions The MSKD is feasible in patients with PDAC and, although not powered for definitive outcomes, shows trends in improved PFS and OS when combined with gemcitabine, nab‐paclitaxel, and cisplatin, without added toxicity or detriment to QOL. Larger studies are required to confirm these findings and establish the value of the MSKD in pancreatic cancer treatment.
Source: Cancer
DOI: 10.1002/cncr.70343
Authors: Gayle S. Jameson, Denise J. Roe, Erkut Borazanci, Diana L. Hanna, Caroline G. P. Roberts, Meredith S. Pelster, Richard C. Frank, Angela T. Alistar, Alan M. Miller, J. Erin Wiedmeier‐Nutor, Sandra D. Algaze, Alison R. Zoller, Sarah J. Hallberg, Betsy C. Wertheim, Keehoon Lee, Derek Cridebring, Joshua D. Rabinowitz, Stephen Gately, Jennifer Keppler, Sunil Sharma, Daniel D. Von Hoff, Drew W. Rasco
Institutions: HonorHealth, University of Arizona Cancer Center, Arizona State University, University of Southern California, USC Norris Comprehensive Cancer Center, Sarah Cannon, Nuvance Health, Morristown Medical Center, Atlantic Health System, Translational Drug Development (United States), Mayo Clinic, Mayo Clinic Hospital, Mayo Clinic Comprehensive Cancer Center (Arizona), Translational Genomics Research Institute, Ludwig Cancer Research, Princeton University, Ludwig Cancer Research, City Of Hope National Medical Center, City of Hope, South Texas Accelerated Research Therapeutics
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
OpenAlex ID: W7135014288