Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

resectable (stages 1 and 2)

1st line – surgical resection

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ACUTE
|
resectable (stages 1 and 2)
1st line – 

surgical resection

Surgical resection is the preferred treatment in patients with resectable disease.[42]​​​​

The nature and extent of the surgery depends on the location and site of the tumour.

The most widely used procedures are the proximal pancreaticoduodenectomy with antrectomy (Kausch-Whipple procedure) or the pylorus-preserving pancreaticoduodenectomy (Traverso-Longmire procedure) for tumours in the head of the pancreas.

Pylorus-preserving pancreaticoduodenectomy may lead to similar quality of life and survival compared with Kausch-Whipple pancreaticoduodenectomy.[78][112] [ Cochrane Clinical Answers logo ]

Extended lymphadenectomy is associated with increases in adverse effects compared with standard lymphadenectomy, without conferring any survival benefit.[81]

Plus – pancreatic enzyme replacement ± olanzapine

Back
ACUTE
|
resectable (stages 1 and 2)
Plus – 

pancreatic enzyme replacement ± olanzapine

Treatment recommended for ALL patients in selected patient group

Pancreatic enzyme supplements may be considered to maintain weight and increase quality of life, together with attention to dietary intake and additional nutritional supplements.[17]​​[42]​​​[125]​​

Patients should be offered nutritional evaluation by a registered dietitian, if available.[1]​​​

Patients with cancer-related anorexia may benefit from daily low-dose olanzapine.[1]

Primary options

pancreatin: dose depends on brand; consult specialist for guidance on dose

OR

olanzapine: 2.5 mg orally once daily

Consider – preoperative biliary stenting

Back
ACUTE
|
resectable (stages 1 and 2)
Consider – 

preoperative biliary stenting

Additional treatment recommended for SOME patients in selected patient group

Patients with symptoms of cholangitis (or whose definitive surgery is delayed by >10 days due to logistical reasons) may require an internal biliary stent. If a stent is placed before surgery, a self-expanding metal stent should be placed endoscopically.[42]​​​​

A temporary stent is also recommended in patients undergoing neoadjuvant induction therapy before surgery, in the setting of a clinical trial.

Routine stenting of patients with jaundice before resection is not recommended; there is no improvement in surgical outcome, and it may increase the risk of infective complications.[42]​​​​[88]

Consider – neoadjuvant radiotherapy or chemoradiotherapy

Back
ACUTE
|
resectable (stages 1 and 2)
Consider – 

neoadjuvant radiotherapy or chemoradiotherapy

Additional treatment recommended for SOME patients in selected patient group

Neoadjuvant therapy (treatment given prior to surgery to reduce the size or extent of the tumour, in order to enhance chances of successful surgical removal of all tumour tissue) remains under investigation in pancreatic cancer.

Neoadjuvant combination chemotherapy or fluorouracil-based chemoradiotherapy can be offered to: patients in whom there is a clinical suspicion (but no radiological evidence) of metastatic disease; patients with borderline performance status who could improve with systemic therapy. In one randomised controlled trial of 246 patients with resectable or borderline resectable pancreatic cancer, neoadjuvant chemoradiotherapy, followed by surgery and adjuvant chemotherapy, did not confer a significant overall survival benefit compared with immediate surgery followed by adjuvant chemotherapy. It was, however, associated with significantly better disease-free survival.[93]

Technically unresectable tumours are rarely rendered resectable by neoadjuvant therapy.[94][95]

Due to limited evidence, there is no standard neoadjuvant regimen. Treatment approaches vary, and subsequent chemoradiotherapy is sometimes included.[1]

Preferred options for neoadjuvant therapy include the FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or modified-dose FOLFIRINOX, or gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel), with or without subsequent chemoradiotherapy.[1]

For known BRCA1/2 or PALB2 mutations, FOLFIRINOX, modified-dose FOLFIRINOX, or gemcitabine plus cisplatin, with or without subsequent chemoradiotherapy, is recommended.[1]

See local specialist protocol for dosing guidelines.

Primary options

FOLFIRINOX

oxaliplatin

and

fluorouracil

and

irinotecan

and

folinic acid

OR

gemcitabine

and

paclitaxel albumin-bound

OR

gemcitabine

and

cisplatin

Plus – adjuvant chemotherapy

Back
ACUTE
|
resectable (stages 1 and 2)
|
completely resected
Plus – 

adjuvant chemotherapy

Treatment recommended for ALL patients in selected patient group

Adjuvant therapy is treatment given after surgery to minimise the risk of relapse due to occult disease. Adjuvant therapy has been shown to improve overall survival in both control and experimental groups in phase 3 clinical trials.[89]​ Patients with resected pancreatic cancer who did not receive neoadjuvant therapy should be offered 6 months of adjuvant chemotherapy.[94]

First-line options for adjuvant therapy include mFOLFIRINOX (a modified combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin), or doublet therapy with gemcitabine plus capecitabine.[1][94] 

Other recommended regimens include: gemcitabine monotherapy; fluorouracil plus folinic acid; and capecitabine monotherapy.[1][94]

Adjuvant doublet regimen of gemcitabine plus capecitabine is also recommended by the UK National Institute for Health and Care Excellence (NICE), in the absence of concerns for toxicity or tolerance.[42]​​​ One multi-centre, open-label randomised trial of 732 patients with resected pancreatic ductal adenocarcinoma found that adjuvant therapy with capecitabine plus gemcitabine significantly improved survival compared with gemcitabine monotherapy (28.0 vs. 25.5 months).[96]​​

See local specialist protocol for dosing guidelines.

Primary options

mFOLFIRINOX

oxaliplatin

and

fluorouracil

and

irinotecan

and

folinic acid

OR

gemcitabine

and

capecitabine

OR

gemcitabine

OR

fluorouracil

and

folinic acid

OR

capecitabine

Consider – adjuvant chemoradiotherapy

Back
ACUTE
|
resectable (stages 1 and 2)
|
incompletely resected
Consider – 

adjuvant chemoradiotherapy

Additional treatment recommended for SOME patients in selected patient group

Adjuvant chemoradiotherapy remains controversial in incompletely resected cancers. Data from the ESPAC-1 trial and one meta-analysis suggest that chemoradiotherapy seems to prolong survival only in incompletely excised (R1 or R2 resection) cancers.[97]​​[98] When choice of treatment is chemoradiotherapy, fluorouracil-based chemoradiotherapy with additional systemic gemcitabine is recommended.[99][100][101]

Adjuvant chemotherapy or chemoradiotherapy should only be considered in patients who have adequately recovered from surgery.[42]​​​ Treatment should ideally be initiated within 4 to 8 weeks of surgery. However, data relating to the timing of adjuvant chemotherapy suggest that post-operative treatment delays of up to 12 weeks do not adversely affect outcomes, provided 6 cycles of adjuvant chemotherapy are completed.[102]

The role of adjuvant chemotherapy in patients who received neoadjuvant chemotherapy is under investigation.

See local specialist protocol for dosing guidelines.

Primary options

fluorouracil

and

folinic acid

and

gemcitabine

locally advanced unresectable (stage 3)

1st line – endoscopic stent insertion or palliative surgery

Back
ACUTE
|
locally advanced unresectable (stage 3)
1st line – 

endoscopic stent insertion or palliative surgery

Locally advanced unresectable disease includes tumours involving nearby structures to an extent that renders them unresectable despite the absence of evidence of metastatic disease. Metastasis to a regional lymph node beyond the field of resection is considered unresectable.[1]​​​

Endoscopic palliation is preferred over surgical approaches.

Patients with biliary obstruction should be offered palliative treatment with endoscopic metal stent insertion into the bile duct.[1]​​ Percutaneous biliary drainage (with subsequent internalisation of the drain) or open-biliary enteric bypass may be considered in selected patients with a longer life expectancy.[1]​​ 

Palliative gastrojejunostomy may be appropriate for patients with gastric outlet or duodenal obstruction and good performance status. If a patient has poor performance status, enteral stenting or venting percutaneous endoscopic gastrostomy should be considered. Biliary drainage should be assured before enteral stent placement.[1] If a patient is not a surgical candidate, endoscopic ultrasound-guided gastrojejunostomy should be considered.[1]

Plus – chemotherapy or chemoradiotherapy or stereotactic body radiotherapy or immunotherapy

Back
ACUTE
|
locally advanced unresectable (stage 3)
Plus – 

chemotherapy or chemoradiotherapy or stereotactic body radiotherapy or immunotherapy

Treatment recommended for ALL patients in selected patient group

After relief of biliary obstruction and, if required, gastric obstruction, systemic treatment with combination chemotherapy or chemoradiotherapy is given to control the tumour.

Patients with good performance status appear to benefit from the FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or modified-dose FOLFIRINOX, gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel), or the NALIRIFOX regimen (liposomal irinotecan, fluorouracil, folinic acid, oxaliplatin).[1]​​​[105]​​[106][107][108]​​​​ [ Cochrane Clinical Answers logo ] Although the NALIRIFOX regimen is advantageous over gemcitabine plus nab-paclitaxel, no distinct advantage over the FOLFIRINOX regimen has been noted.[1]

For known BRCA1/2 or PALB2 mutations, FOLFIRINOX, modified FOLFIRINOX, or gemcitabine plus cisplatin is recommended.[1]

Alternative regimens include: gemcitabine monotherapy; capecitabine monotherapy; gemcitabine plus erlotinib; gemcitabine plus capecitabine; capecitabine plus oxaliplatin (CapeOx); fluorouracil plus folinic acid plus oxaliplatin (OFF); fluorouracil monotherapy; gemcitabine plus nab-paclitaxel plus cisplatin; or gemcitabine plus docetaxel plus capecitabine (GTX).[1]

​​The addition of erlotinib (an oral HER1/EGFR tyrosine kinase inhibitor) remains controversial. Initial studies suggested a very modest survival benefit (2 weeks), but no significant difference in overall survival was observed when patients with locally advanced pancreatic cancer were randomised to gemcitabine or gemcitabine plus erlotinib.[109][110][111]

Patients with intermediate performance status may be treated with capecitabine, gemcitabine, or gemcitabine plus nab-paclitaxel.

Monotherapy with gemcitabine is recommended for the first-line treatment for patients with poor performance status or an unfavourable comorbidity profile. Other first-line treatment options include capecitabine or fluorouracil.[1]

Chemoradiotherapy or a short course of stereotactic body radiotherapy (SBRT) can be offered to patients with good or intermediate performance status with local progression (without distant metastases) during or after chemotherapy, or to those who responded to chemotherapy as consolidation therapy to further improve local control.[1]​​ Studies investigating the role of chemoradiotherapy or SBRT in the management of locally advanced pancreatic cancer are ongoing.

Other first-line regimens recommended by the National Comprehensive Cancer Network that can be used under certain circumstances for patients with good or intermediate performance status include: dabrafenib plus trametinib for patients with BRAF V600E mutation; entrectinib, larotrectinib, or repotrectinib for patients with tumours that have a neurotrophic tyrosine receptor kinase gene fusion; pembrolizumab for patients who have tested positive for mismatch repair deficiency or microsatellite instability; and selpercatinib for patients who have tumours with RET gene fusion.[1]

See local specialist protocol for dosing guidelines.

Primary options

FOLFIRINOX

oxaliplatin

and

fluorouracil

and

irinotecan

and

folinic acid

OR

NALIRIFOX

irinotecan liposomal

and

fluorouracil

and

folinic acid

and

oxaliplatin

OR

gemcitabine

and

paclitaxel albumin-bound

OR

gemcitabine

OR

capecitabine

OR

gemcitabine

-- AND --

cisplatin

or

capecitabine

or

erlotinib

OR

fluorouracil

OR

OFF

fluorouracil

and

folinic acid

and

oxaliplatin

OR

CapeOx

capecitabine

and

oxaliplatin

OR

gemcitabine

and

paclitaxel albumin-bound

and

cisplatin

OR

GTX

gemcitabine

and

docetaxel

and

capecitabine

Secondary options

dabrafenib

and

trametinib

OR

entrectinib

OR

larotrectinib

OR

repotrectinib

OR

pembrolizumab

OR

selpercatinib

Plus – pain management + pancreatic enzyme replacement ± olanzapine

Back
ACUTE
|
locally advanced unresectable (stage 3)
Plus – 

pain management + pancreatic enzyme replacement ± olanzapine

Treatment recommended for ALL patients in selected patient group

Pancreatic pain (abdominal and back pain) can be a troublesome symptom to control.

Pain control should be commenced along 'the analgesic ladder', but opioids are often required to control the pain.

Local pain-management protocols should be consulted for suggested analgesics. Dosing has to be titrated according to individual requirements and symptom relief versus adverse effect balances.

Additional options include using appropriate long-acting opioid analgesics, percutaneous (or endoscopic ultrasound-guided) coeliac block, endoscopic ultrasound-guided coeliac plexus neurolysis (fluoroscopic- or CT-guided if unavailable), or splanchnicectomy.[1][42]​​​​​[119]​​​[120][121][122][123]​​ [ Cochrane Clinical Answers logo ] ​ However, NICE in the UK recommends against using splanchnicectomy in people with pancreatic cancer.[42]​​​​[Evidence C]​ The American Society for Gastrointestinal Endoscopy (ASGE) suggests coeliac plexus neurolysis as an adjunct to analgesics in patients with unresectable pancreatic cancer and abdominal pain.[124]

Pancreatic enzyme supplements should be used to maintain weight and increase quality of life, together with attention to dietary intake and additional nutritional supplements.[17]​​[125]

Patients should be offered nutritional evaluation by a registered dietitian, if available.[1]​​​

Patients with cancer-related anorexia may benefit from daily low-dose olanzapine.[1]

Primary options

pancreatin: dose depends on brand; consult specialist for guidance on dose

OR

olanzapine: 2.5 mg orally once daily

metastatic (stage 4)

1st line – endoscopic stent insertion or palliative surgery

Back
ACUTE
|
metastatic (stage 4)
1st line – 

endoscopic stent insertion or palliative surgery

Endoscopic palliation is preferred over surgical approaches.

Patients with biliary obstruction should be offered palliative treatment with endoscopic metal stent insertion into the bile duct.[1]​​ Percutaneous biliary drainage (with subsequent internalisation of the drain) or open-biliary enteric bypass may be considered in selected patients with a longer life expectancy.[1]​​​

Palliative gastrojejunostomy may be appropriate for patients with gastric outlet or duodenal obstruction and good performance status. If a patient has poor performance status, enteral stenting or venting percutaneous endoscopic gastrostomy should be considered. Biliary drainage should be assured before enteral stent placement.[1]​​​ If a patient is not a surgical candidate, endoscopic ultrasound-guided gastrojejunostomy should be considered.[1]

Plus – chemotherapy or immunotherapy

Back
ACUTE
|
metastatic (stage 4)
Plus – 

chemotherapy or immunotherapy

Treatment recommended for ALL patients in selected patient group

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), capecitabine, or erlotinib (an oral HER1/EGFR tyrosine kinase inhibitor) may be added to gemcitabine, with proactive dose and schedule adjustments to minimise adverse effects.[43]

The preferred regimen for patients with good performance status is FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or modified-dose FOLFIRINOX, or gemcitabine plus nab-paclitaxel.[1]​​​[42]​​[113]​​​​ [ Cochrane Clinical Answers logo ] ​​​​​ In phase 3 trials, both regimens improved survival compared with gemcitabine alone.[105]​​[106] FOLFIRINOX is recommended as a first-line treatment by the UK National Institute for Health and Care Excellence (NICE) for people who are still active or only slightly restricted from physical activity (Eastern Cooperative Oncology Group performance status of 0-1).[42]​​​ NICE recommends gemcitabine plus nab-paclitaxel for untreated metastatic adenocarcinoma of the pancreas in adults, restricted to use where other combination treatments are unsuitable and gemcitabine monotherapy would otherwise be given.[114]

The NALIRIFOX regimen (liposomal irinotecan, fluorouracil, folinic acid, oxaliplatin) is another tolerable option for patients with metastatic disease with good performance status.[1]​​​[113][108] One randomised open-label phase 3 study (NAPOLI-3) has reported statistically significant improvement in overall survival and progression-free survival with NALIRIFOX compared with gemcitabine plus nab-paclitaxel in patients with metastatic pancreatic cancer.[115]​​[116]​ Although the NALIRIFOX regimen is advantageous over gemcitabine plus nab-paclitaxel, no distinct advantage over the FOLFIRINOX regimen has been noted.[1]​​

For known BRCA1/2 or PALB2 mutations, FOLFIRINOX, modified FOLFIRINOX, or gemcitabine plus cisplatin is recommended.[1]

Other recommended options for patients with metastatic disease with good performance status include: gemcitabine monotherapy; gemcitabine plus erlotinib; gemcitabine plus capecitabine; gemcitabine plus nab-paclitaxel plus cisplatin; capecitabine plus oxaliplatin (CapeOx); fluorouracil plus folinic acid plus oxaliplatin (OFF); or gemcitabine plus docetaxel plus capecitabine (GTX).[1]

Patients with intermediate performance status may be treated with: gemcitabine plus nab-paclitaxel; capecitabine monotherapy; gemcitabine monotherapy; fluorouracil plus folinic acid plus oxaliplatin (FOLFOX); fluorouracil plus folinic acid plus irinotecan (FOLFIRI); or capecitabine plus oxaliplatin (CapeOx).[1]

The preferred option for patients with metastatic cancer having a poor performance status is palliative and best supportive care, as chemotherapy often provides limited benefit.[1]​ Treatment options that may be considered include gemcitabine, capecitabine, or fluorouracil monotherapy.[1]

Other first-line regimens recommended by the National Comprehensive Cancer Network that can be used under certain circumstances for patients with good or intermediate performance status include: dabrafenib plus trametinib for patients with BRAF V600E mutation; entrectinib, larotrectinib, or repotrectinib for patients with tumours that have a neurotrophic tyrosine receptor kinase gene fusion; pembrolizumab for patients who have tested positive for mismatch repair deficiency or microsatellite instability; and selpercatinib for patients who have tumours with RET gene fusion. Except for selpercatinib, all other options can be considered in patients with poor performance status.[1]

See local specialist protocol for dosing guidelines.

Primary options

gemcitabine

and

paclitaxel albumin-bound

OR

FOLFIRINOX

oxaliplatin

and

fluorouracil

and

irinotecan

and

folinic acid

OR

NALIRIFOX

irinotecan liposomal

and

fluorouracil

and

folinic acid

and

oxaliplatin

OR

gemcitabine

OR

gemcitabine

-- AND --

cisplatin

or

capecitabine

or

erlotinib

OR

gemcitabine

and

paclitaxel albumin-bound

and

cisplatin

OR

GTX

gemcitabine

and

docetaxel

and

capecitabine

OR

CapeOx

capecitabine

and

oxaliplatin

OR

capecitabine

OR

OFF or FOLFOX

oxaliplatin

and

fluorouracil

and

folinic acid

OR

FOLFIRI

fluorouracil

and

folinic acid

and

irinotecan

OR

fluorouracil

Secondary options

dabrafenib

and

trametinib

OR

entrectinib

OR

larotrectinib

OR

repotrectinib

OR

pembrolizumab

OR

selpercatinib

Plus – pain management + pancreatic enzyme replacement ± olanzapine

Back
ACUTE
|
metastatic (stage 4)
Plus – 

pain management + pancreatic enzyme replacement ± olanzapine

Treatment recommended for ALL patients in selected patient group

Pancreatic pain (abdominal and back pain) can be a troublesome symptom to control.

Pain control should be commenced along 'the analgesic ladder', but opioids are often required to control the pain.

Local pain-management protocols should be consulted for suggested analgesics. Dosing has to be titrated according to individual requirements and symptom relief versus adverse effect balances.

Additional options include using appropriate long-acting opioid analgesics, percutaneous (or endoscopic ultrasound-guided) coeliac block, endoscopic ultrasound-guided coeliac plexus neurolysis (fluoroscopic- or CT-guided if unavailable), or splanchnicectomy.[1]​​[42]​​​[119]​​​​​​[120][121][122][123] [ Cochrane Clinical Answers logo ] ​ However, NICE in the UK recommends against using splanchnicectomy in people with pancreatic cancer.[42]​​​​[Evidence C]​ The American Society for Gastrointestinal Endoscopy (ASGE) suggests coeliac plexus neurolysis as an adjunct to analgesics in patients with unresectable pancreatic cancer and abdominal pain.[124]

Palliative radiotherapy may be administered to relieve symptoms of obstruction, bleeding, or pain refractory to analgesia.[1]​​ 

Pancreatic enzyme supplements should be used to maintain weight and increase quality of life, together with attention to dietary intake and additional nutritional supplements.[17]​​[125]​​

Patients should be offered nutritional evaluation by a registered dietitian, if available.[1]​​ 

Patients with cancer-related anorexia may benefit from daily low-dose olanzapine.[1]

Primary options

pancreatin: dose depends on brand; consult specialist for guidance on dose

OR

olanzapine: 2.5 mg orally once daily

Consider – olaparib

Back
ACUTE
|
metastatic (stage 4)
Consider – 

olaparib

Additional treatment recommended for SOME patients in selected patient group

Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, is approved in the US as a maintenance treatment for use in adults with metastatic pancreatic adenocarcinoma and confirmed or suspected deleterious BRCA1 or BRCA2 germline mutations who have not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. One phase 3 trial showed that in patients whose disease had not progressed during first-line platinum-based chemotherapy, maintenance olaparib significantly increased progression-free survival compared with placebo (7.4 months compared to 3.8 months), in patients with a germline BRCA1 or BRCA2 mutation.[117] No significant benefit with respect to overall survival has been observed.[118] There was no difference in overall mortality between the olaparib and placebo groups at an interim data analysis. Adverse events were more common in the olaparib group than the placebo group and included fatigue, nausea, anaemia, abdominal pain, diarrhoea, decreased appetite, constipation, vomiting, back pain, and arthralgia.[117]

Platinum-sensitive patients with a germline BRCA1 or BRCA2 mutation may continue treatment with chemotherapy or proceed to maintenance therapy with olaparib. The patient and clinician should make a shared decision, considering response to chemotherapy, toxicities, patient preference, clinical evidence, and cost.[43]

See local specialist protocol for dosing guidelines.

Primary options

olaparib

Consider – metastasis-directed therapy

Back
ACUTE
|
metastatic (stage 4)
Consider – 

metastasis-directed therapy

Additional treatment recommended for SOME patients in selected patient group

Under rare circumstances, metastasis-directed therapy may be considered at a high-volume centre for patients with indolent/oligometastatic disease.[1]

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer