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Pancreas adjuvant gemcitabine

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The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 to 6

Day 1, 8, 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
Gemcitabine 1,000 mg/m2 (IV infusion) in 100 mL to 500 mL sodium chloride 0.9% over 30 minutes
Frequency:
28 days 
Cycles:
6 

The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 to 6

Day 1, 8, 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
Gemcitabine 1,000 mg/m2 (IV infusion) in 100 mL to 500 mL sodium chloride 0.9% over 30 minutes
Frequency:
28 days 
Cycles:
6 

Indication: 

  • Adjuvant pancreatic adenocarcinoma following recovery and within 3 months of surgery.

Note: 

Venous access required

IV cannula (IVC) or central venous access device (CVAD) is required to administer this treatment.

Read more about central venous access device line selection
Emetogenicity LOW

Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy.

Ensure that patients also have sufficient antiemetics for breakthrough emesis:

Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR

Prochlorperazine 10 mg PO every 6 hours when necessary.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Pulmonary toxicity

Dyspnoea developing within hours of the infusion has been reported in about 10% of patients treated with gemcitabine.

Read more about pulmonary toxicity associated with anti-cancer drugs.
Growth factor support

G-CSF (short or long-acting) is available on the PBS for chemotherapy induced neutropenia depending on clinical indication and/or febrile neutropenia risk.  

Access the PBS website opens in a new tab or window
Blood tests

FBC, EUC, eGFR and LFTs at baseline. Repeat FBC prior to each treatment, EUC, eGFR, and LFTs prior to each cycle or as clinically indicated.
Hepatitis B screening and prophylaxis

Routine screening for HBsAg and anti-HBc is recommended prior to initiation of treatment. Prophylaxis should be determined according to individual institutional policy. 

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease. Possible suboptimal response to inactivated vaccines.

For more information about vaccinations in people with cancer refer to the Australian Immunisation Handbook opens in a new tab or window.
Fertility, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of fetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the impact of cancer treatment on fertility opens in a new tab or window
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) opens in a new tab or window unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Note: All dose reductions are calculated as a percentage of the starting dose.

Haematological toxicity
Day 1
ANC x 109/L (pre-treatment blood test)
0.5 to less than 1.0 Delay treatment until recovery
less than 0.5 Delay treatment until recovery and consider reducing gemcitabine by 25% for subsequent cycles
Febrile neutropenia or previous delay for myelosuppression Delay treatment until recovery and consider reducing gemcitabine by 25% for subsequent cycles
Prolonged recovery greater than two weeks delay or 3rd delay for myelosuppression Delay treatment until recovery, consider reducing gemcitabine by 50% for subsequent cycles or cease
Platelets x 109/L (pre-treatment blood test)
75 to less than 100 Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well
50 to less than 75 Delay treatment until recovery
less than 50 Delay treatment until recovery and consider reducing gemcitabine by 25% for subsequent cycles
Day 8 and 15
ANC x 109/L (pre-treatment blood test)
0.5 to less than 1.0 Consider reducing gemcitabine by 25% and proceed with treatment.
less than 0.5 Omit dose*
Platelets x 109/L (pre-treatment blood test)
50 to less than 100 Consider reducing gemcitabine by 25% and proceed with treatment.
less than 50 Omit dose*

* Omit dose and proceed with the next treatment on the scheduled date if recovered
Kidney dosing recommendations 
  • Suggested dose modifications are based on the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD).
  • Where one or more drugs in a protocol is recommended to be avoided, consider using a clinically appropriate alternative treatment protocol instead.
  • Before dose adjusting or omitting a drug, consider treatment intent.
  • In kidney replacement therapy consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing. 
  • For complete information on individual drug recommendations please review the individual drug monograph in the ADDIKD guideline.
eGFR
(mL/min/1.73m2)		 Gemcitabine
≥ 60

Full dose
45 - 59

Full dose

Potential for increased risk of adverse events
30 - 44

Full dose

Potential for increased risk of adverse events
15 - 29

Full dose

Potential for increased risk of adverse events
< 15
(without kidney replacement therapy)

Consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing.
Hepatic impairment
Hepatic dysfunction
Moderate Reduce gemcitabine by 25%
Severe No data for gemcitabine
Mucositis and stomatitis
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce gemcitabine by 25%
3rd occurrence: Reduce gemcitabine by 50%
4th occurrence: Omit gemcitabine
Grade 3 or Grade 4 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce gemcitabine by 50%
2nd occurrence: Omit gemcitabine
Cease gemcitabine if any of the following develop:
  • pulmonary toxicity
  • haemolytic uraemic syndrome (HUS)
  • severe cutaneous adverse reactions (SCARs) e.g. Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP)

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources: 

For more information see References & Disclaimer.

Gemcitabine
  Interaction Clinical management
Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs) Additive nephrotoxicity Avoid combination or monitor kidney function closely

Warfarin		 Increased anticoagulant effect/increased bleeding risk due to decreased hepatic metabolism of warfarin and decreased synthesis of clotting factors Monitor INR regularly and adjust warfarin dosage as appropriate
Cytidine deaminase (CDA) inhibitors (e.g. cedazuridine) Increased effect/toxicity of gemcitabine possible due to reduced clearance Avoid combination or monitor for increased gemcitabine  effect/toxicity
General
  Interaction Clinical management
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update. opens in a new tab or window

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter or address chemical compatibilities related to IV drug preparation and administration. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Day 1, 8 and 15

Approximate treatment time: 60 minutes

Any toxicity grade 2 or greater may require dose reduction, delay or omission of treatment and review by medical officer before commencing treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Administer antiemetics if required.

Gemcitabine 

Administer gemcitabine (irritant):
  • via IV infusion over 30 minutes
    • if pain develops along the vein, verify the drug has not extravasated
    • further dilution (using a second saline line), warmth or temporarily slowing the infusion may help
  • flush with ~ 100 mL of sodium chloride 0.9% 
  • prolonged infusion times have been shown to increase toxicity.

Remove IV cannula and/or deaccess TIVAD or CVAD. 

Continue safe handling precautions until 7 days after completion of drug(s).

Discharge information

Antiemetics - as/if prescribed.

Patient information

Ensure patient receives protocol patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting
Flu-like symptoms
Taste and smell alteration

Read more about taste and smell changes

Early (onset days to weeks)
Diarrhoea

Read more about treatment induced diarrhoea
Oral mucositis and stomatitis

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following anti-cancer treatment, radiation therapy to the head, neck or oesophagus, and high-dose chemotherapy followed by a blood and marrow transplant (BMT).

Read more about oral mucositis and stomatitis
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash
Fatigue

Read more about fatigue
Fluid retention and oedema

An excess amount of fluid around the cells, tissues or serous cavities of the body, leading to swelling.
Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs) have been reported with this treatment. SCARs are serious drug reactions involving the skin which may be life-threatening, or even fatal, and include conditions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP).

If SCARs occur, discontinue treatment immediately and seek specialist opinion to determine differential diagnosis so that appropriate supportive treatment can be administered.

Late (onset weeks to months)
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia
Alopecia - partial

Hair thinning and/or patchy hair loss. Patients can also experience mild to moderate discomfort of the hair follicles, and rarely pain as the hair is falling out.

Read more about alopecia and scalp cooling
Pulmonary toxicity

Pulmonary toxicity may include damage to the lungs, airways, pleura and pulmonary circulation. 

Read more about pulmonary toxicity associated with anti-cancer drugs
Haemolytic uraemic syndrome (HUS)

A rare but serious acute syndrome characterised by haemolysis of red blood cells and kidney failure.

Read more about haemolytic uraemic syndrome (HUS)

eviQ is currently updating the way information is presented in the evidence section to improve usability, consistency and facilitate easier update and maintenance. An updated evidence template is being implemented in a staged approach, first across new protocols, then existing protocols as they are reviewed. Find out more

The evidence supporting this protocol is provided by two phase III randomised controlled trials, CONKO-001r and (ESPAC)-3.r

Between July 1998 and December 2004, a total of 368 patients with gross complete (RO or R1) resection of pancreatic cancer were enrolled into the CONKO-001 trial. Patients received adjuvant chemotherapy with 6 cycles of gemcitabine (1000 mg/m2) on days 1, 8, and 15 every 4 weeks (n=179), or observation (n=175). The primary end point was disease-free survival; secondary end points were overall survival, toxicity, and quality of life.r

The (ESPAC)-3 trial was an international RCT conducted in 159 pancreatic cancer centres. Between July 2000 and January 2007, a total of 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection were randomised to receive either fluorouracil (5FU) plus folinic acid (FA) (FA 20 mg/m2 IV followed by 5FU 425 mg/m2 IV d1-5 every 28 days) (n=551) or gemcitabine (1000 mg/m2 IV d1, 8 ,15 every 28 days) (n=537) for 6 months. The primary end point was overall survival; secondary end points were toxicity, progression-free survival, and quality of life.r

Efficacy

In the CONKO-001 trial, after a median follow-up of 53 months, 74% in the gemcitabine group and 92% in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% CI 11.4-15.3) and 6.9 months in the control group (95% CI 6.1-7.8; p<0.001). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection.r

Final results presented at ASCO 2008 showed that gemcitabine significantly improves OS and the estimated survival at 3 and 5 years was 36.5% and 21.0% for gemcitabine patients vs. 19.5% and 9.0% for observation only patients respectively.r

Disease-free and Overall Survival (Intention-to-Treat Analysis)r

© JAMA 2007

In the (ESPAC)-3 trial, after a median follow-up of 34.2 months, the median survival was 23.0 (95% CI 21.1-25.0) months for 5FU/FA arm and 23.6 (95% CI 21.4-26.4) months for the gemcitabine arm (HR=0.94; 95% CI 0.81-1.08). There were no significant differences in either progression-free survival or global quality-of-life scores between treatment groups.r

Overall and Progression-free Survivalr

© JAMA 2010

Toxicity

Grade 3 or 4 toxicities rarely occurred with gemcitabine and there was no difference in quality of life (by Spitzer index) between gemcitabine and the observation group in the CONKO-001 trial.r

Toxicityr

© JAMA 2007

In the (ESPAC)-3 trial, seventy-seven patients (14%) receiving 5FU/FA had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (p<0.001).r

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Version 8

Date Summary of changes
04/09/2024

Severe cutaneous adverse reactions (SCARs) added to side effects and dose modification section updated with dermatological reactions as per gemcitabine product information. Version increased to V.8.

Version 7

Date Summary of changes
31/01/2024

Protocol assessed by eviQ medical oncology reference committee and deemed suitable to be reviewed as required. Flag added, review date removed and version number increased to V.7. Read more about as required review protocol status in this factsheet.

Version 6

Date Summary of changes
07/09/2023

Protocol updated with ADDIKD guideline recommendations. New kidney dosing recommendation table added to dose modification section.

PDF of previous protocol.

Version number changed to V.6.

Version 5

Date Summary of changes
08/10/2019 Clinical information updated with PBS expanded indications for GCSF. 
20/10/2022

Protocol reviewed electronically by Medical Oncology Reference Committee. No changes. Next review 4 years.

Version 4

Date Summary of changes
25/11/2011 New protocol taken to Medical Oncology Reference Committee meeting.
04/05/2012 Approved and published on eviQ.
13/09/2013 Protocol reviewed by reference committee via email.
No changes and next review in 2 years.
01/11/2013 Haematological dose modifications updated.
16/12/2015 Protocol reviewed electronically by Medical Oncology Reference committee. No changes and next review in 2 years.
10/11/2016 The following changes made post Medical Oncology Reference Committee meeting held on 21 October 2016: link to AGITG and ANZCTR added. 
31/05/2017 Transferred to new eviQ website. Version number changed to V.3.
16/02/2018 Protocol reviewed at Medical Oncology Reference Committee Meeting.
Note added to indications. Link to ID 1945 Pancreas adjuvant capecitabine and gemcitabine protocol added.
Review in 5 years.
10/05/2018

Haematological dose modifications updated as per consensus of the expert clinician group. Version number changed to V.4.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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First approved:
Last reviewed:
Review due:
As required

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/1218

15 Jun 2025