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Most people with pancreatic cancer lose muscle and weight in a way food alone cannot reverse, and that wasting is a common reason chemotherapy is cut or stopped. A 2024 trial showed an antibody against the hormone GDF-15 restored weight and activity in twelve weeks, a third of the patients having pancreatic cancer. The proposal is to test it inside the chemotherapy trials, not alongside them.
Fearon's 2011 consensus defined cachexia as ongoing skeletal muscle loss not fully reversible by nutritional support, with weight loss over 5 percent (or over 2 percent with low body mass index or sarcopenia) as the diagnostic criterion and stages from pre-cachexia to refractory. Ponsegromab (Groarke 2024) in 187 patients with raised GDF-15 (32 percent pancreatic cancer) produced dose-dependent weight gain versus placebo of 1.22 to 2.81 kg at 12 weeks, with better appetite and measured physical activity at 400 mg and fewer adverse events than placebo. In pancreatic cancer specifically, cachexia and exocrine insufficiency (enzyme replacement reaching 21.7 percent of UK patients, Roberts 2019) determine whether patients receive and tolerate FOLFIRINOX-class regimens, yet cachexia trials are run in mixed-cancer populations with weight as the endpoint and chemotherapy trials exclude patients with significant weight loss. The proposal is a factorial or platform design in first-line pancreatic cancer: chemotherapy backbone with or without a GDF-15 antibody, with mandatory enzyme replacement and dietetic support in all arms, and co-primary endpoints of relative dose intensity delivered and lean mass at 12 weeks, with overall survival as the key secondary.
The first drug to reverse cancer cachexia mechanistically rather than by appetite stimulation, in a disease where weight loss stops chemotherapy being delivered; the phase 3 programme and the question of survival remain.
Enzyme replacement is cheap, guideline-recommended (NICE NG85) and under-prescribed; the National Pancreatic Cancer Audit now reports the prescribing rate as a performance indicator, which the UK and NHS page tracks.
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Shares Pancreatic enzyme replacement by default: prescribe at diagnosis, audit the rate, and run the trial that settles survival, Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study, Older and multimorbid patients are excluded and undertreated, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question and the tag pancreatic-evidence.
Shares Pancreatic enzyme replacement by default: prescribe at diagnosis, audit the rate, and run the trial that settles survival, Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Gemcitabine + nab-paclitaxel, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Performance status (ECOG, Karnofsky), Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares FOLFIRINOX / mFOLFIRINOX, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Gemcitabine + nab-paclitaxel, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares FOLFIRINOX / mFOLFIRINOX, Trial design, endpoints and cost, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares FOLFIRINOX / mFOLFIRINOX, Trial design, endpoints and cost, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.