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Locally advanced unresectable pancreatic ductal adenocarcinoma: the decisions you may face

6 treatment settings, 4 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Advanced, first line

Induction chemotherapy

Modified FOLFIRINOX or gemcitabine plus nab-paclitaxel for four to six months, with biliary stenting, pancreatic enzyme replacement and pain control alongside.

The options, in plain words

FOLFIRINOX is a four-drug chemotherapy combination that, in 2011, became the first treatment to meaningfully extend life in metastatic pancreatic cancer; it is now the standard before and after surgery.

Gemcitabine plus nab-paclitaxel is the gentler of the two standard chemotherapy backbones for pancreatic cancer, and the base on which most new drugs are being tested.

A small tube placed by endoscope or through the skin reopens a blocked bile duct, relieving jaundice so chemotherapy can be given.

  • Rapid symptom relief
  • Enables chemotherapy dosing
Also referenced:Cancer cachexia
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Cholangitis and stent occlusion
  • Pre-operative drainage is debated for resectable disease
Questions to ask about this decision
  1. Between FOLFIRINOX / mFOLFIRINOX, Gemcitabine + nab-paclitaxel and Biliary stenting and drainage, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NCCN Guidelines: Pancreatic Adenocarcinoma), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  5. For my situation (induction chemotherapy), which of the standard options do you recommend and why?
    Why: Guideline options include: Modified FOLFIRINOX or gemcitabine plus nab-paclitaxel for four to six months, with biliary stenting, pancreatic enzyme replacement and pain control alongside.
  6. Am I a candidate for FOLFIRINOX / mFOLFIRINOX, Gemcitabine + nab-paclitaxel, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Tumour treating fields

Alternating electric fields delivered through skin arrays added to gemcitabine plus nab-paclitaxel (PANOVA-3), approved in 2026.

The options, in plain words

Wearable electrodes that deliver alternating electric fields disrupting cancer cell division.

  • Non-invasive, minimal systemic toxicity
  • Combinable with any drug

Optune is a wearable device delivering electric fields that disrupt cell division. It is approved for glioblastoma and, in 2026, pancreatic cancer.

Gemcitabine plus nab-paclitaxel is the gentler of the two standard chemotherapy backbones for pancreatic cancer, and the base on which most new drugs are being tested.

The evidence behind it
The main trade-offs on record
  • 18+ hours/day wear
  • Skin irritation
  • Sceptical reception of some trial designs
Questions to ask about this decision
  1. Between Tumour treating fields (TTFields), Optune / Optune Pax (TTFields) and Gemcitabine + nab-paclitaxel, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in PANOVA-3, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Guidelines: Pancreatic Adenocarcinoma), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (tumour treating fields), which of the standard options do you recommend and why?
    Why: Guideline options include: Alternating electric fields delivered through skin arrays added to gemcitabine plus nab-paclitaxel (PANOVA-3), approved in 2026.
  7. Am I a candidate for Optune / Optune Pax (TTFields), Gemcitabine + nab-paclitaxel, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of PANOVA-3 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Consolidation local therapy

4 options

Chemoradiation with capecitabine, stereotactic body radiotherapy or MR-guided ablative radiotherapy after induction chemotherapy for disease that has not spread; LAP07 shows better local control without longer survival.

The options, in plain words

Stereotactic body radiotherapy converges multiple beams with sub-millimetre accuracy to deliver tumour-destroying doses in one to five outpatient sessions, doing the job of surgery for inoperable early lung cancer and for metastases in liver, spine and brain. Tumour size and location limit its use, and late toxicity is a concern near the central airways.

  • Ablative doses with minimal recovery
  • Outpatient

An MR-linac is a radiation machine with an MRI scanner built in, so images taken during setup let the plan be re-optimised in minutes to that day's anatomy. It allows tighter margins and higher doses in pancreatic and prostate cancer, but treatment is slow and costly, and whether daily adaptation improves cure rates rather than only toxicity is unproven.

  • Tighter margins, dose escalation in pancreas

Capecitabine (Xeloda) is a tablet form of the chemotherapy fluorouracil. It is a backbone of treatment for bowel cancer and a standard option in advanced breast cancer.

Fewer, larger daily doses instead of the classic five to seven weeks of small ones. Large trials in breast and prostate cancer showed the same control with the same or fewer late effects and far less time in hospital.

  • One to three weeks instead of five to seven
  • Same cancer control in randomised trials
  • Frees machine capacity
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Size and location limits
  • Late toxicity near central airways
  • Slow throughput
  • Cost
  • Long-term follow-up still accruing for the shortest schedules
  • Not suitable where large volumes of normal tissue are treated
  • Requires precise setup
Questions to ask about this decision
  1. Between SBRT / SABR (stereotactic radiotherapy), MR-guided adaptive radiotherapy, Capecitabine and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NCCN Guidelines: Pancreatic Adenocarcinoma), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  5. For my situation (consolidation local therapy), which of the standard options do you recommend and why?
    Why: Guideline options include: Chemoradiation with capecitabine, stereotactic body radiotherapy or MR-guided ablative radiotherapy after induction chemotherapy for disease that has not spread; LAP07 shows better local control without longer survival.
  6. Am I a candidate for Capecitabine, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Conversion surgery

Described in words

Exploration and resection, sometimes with arterial reconstruction, for the minority with stable or responding disease and a normalised CA 19-9 after induction.

The path, in plain words

This setting names no product or technology record yet; the approach above is the standard as written. Ask your team which specific treatments they mean.

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record

No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.

Questions to ask about this decision
  1. Which specific treatments are you proposing for this setting, and what are the alternatives?
    Why: The standard of care here is described in words rather than named products; ask for the names.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NCCN Guidelines: Pancreatic Adenocarcinoma), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  5. For my situation (conversion surgery), which of the standard options do you recommend and why?
    Why: Guideline options include: Exploration and resection, sometimes with arterial reconstruction, for the minority with stable or responding disease and a normalised CA 19-9 after induction.

Add these to your appointment list, or take the full question set for this cancer.

One path named

Irreversible electroporation in selected centres after induction chemotherapy; no randomised evidence.

The path, in plain words

Irreversible electroporation uses short high-voltage pulses that punch permanent holes in tumour cells while sparing nearby vessels and ducts.

  • Safe next to vessels and bile ducts
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • General anaesthesia with paralysis; cardiac synchronisation
  • Limited randomised data
Questions to ask about this decision
  1. Is Irreversible electroporation (NanoKnife) the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
    Why: A single standard does not mean a single choice; timing and trials are decisions too.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NCCN Guidelines: Pancreatic Adenocarcinoma), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  5. For my situation (ablation), which of the standard options do you recommend and why?
    Why: Guideline options include: Irreversible electroporation in selected centres after induction chemotherapy; no randomised evidence.

Add these to your appointment list, or take the full question set for this cancer.

Treat as metastatic disease: switch backbone, daraxonrasib after first-line chemotherapy, clinical trials.

The options, in plain words

NALIRIFOX is a version of FOLFIRINOX using a liposome-wrapped irinotecan, approved in 2024 as a first-line option for metastatic pancreatic cancer.

The first drug that blocks all active RAS variants, approved by the FDA in August 2026 for metastatic pancreatic cancer, where KRAS drives 90% of tumours.

The evidence behind it
  • Metastatic PDAC after one prior line of chemotherapy: daraxonrasib vs investigator's choice chemotherapy

    OS 13.2 vs 6.7 months, HR 0.40.

    Overall survival (months): Daraxonrasib 13.2 vs Chemotherapy (gemcitabine/nab-paclitaxel or mFOLFOX6) 6.7 · HR 0.4 · source
The main trade-offs on record

No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.

Questions to ask about this decision
  1. Between NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV) and Daraxonrasib, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in RASolute 302, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Guidelines: Pancreatic Adenocarcinoma), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (progression), which of the standard options do you recommend and why?
    Why: Guideline options include: Treat as metastatic disease: switch backbone, daraxonrasib after first-line chemotherapy, clinical trials.
  7. Am I a candidate for NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV), Daraxonrasib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of RASolute 302 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.