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Home > Neuroendocrine tumour Advanced - streptozocin and fluorouracil

Neuroendocrine tumour Advanced - streptozocin and fluorouracil

Treatment Overview

Cycle 1 (and all further cycles) - 42 days

Cycle length:
42

streptozocin: 

  • Renal toxicity is dose related and cumulative and may be severe or fatal.
  • Monitor renal function before and after each course of therapy.
  • Mild proteinuria is one of the first signs of renal toxicity and may herald further deterioration of renal function.

Cycle details

Cycle 1 (and all further cycles) - 42 days

Medication Dose Route Days Max Duration
olanzapine * 2.5 mg oral administration 1 to 7
aprepitant 125 mg oral administration 1
aprepitant * 80 mg oral administration 2 to 5
dexamethasone * 12 mg oral administration 1
dexamethasone * 8 mg oral administration 2 to 7
ondansetron 8 mg oral administration 1 to 5
sodium chloride 0.9 % intravenous 1 to 5 120 minutes
streptozocin 500 mg/m² Once daily intravenous 1 to 5 30 minutes
fluorouracil 400 mg/m² Once daily intravenous 1 to 5 15 minutes
ondansetron 8 mg oral administration 1 to 5
cyclIZINE 50 mg Three times daily oral administration 1
docusate sodium + sennoside B 2 Tablet(s) oral administration 1
loperamide 2 mg oral administration 1

streptozocin: 

  • Renal toxicity is dose related and cumulative and may be severe or fatal.
  • Monitor renal function before and after each course of therapy.
  • Mild proteinuria is one of the first signs of renal toxicity and may herald further deterioration of renal function.

Full details

Cycle 1 (and all further cycles) - 42 days

Day: 1

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONE hour prior to chemotherapy. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
  • Some centres may choose to omit pre-chemotherapy dose or advise patient to take the night before chemotherapy if patient has to drive to appointment.
aprepitant 125 mg oral administration
Instructions:
ONE hour prior to chemotherapy.
dexamethasone * 12 mg oral administration
Instructions:

ONE hour prior to chemotherapy with food.
ondansetron 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to streptozocin infusion.
streptozocin 500 mg/m² Once daily intravenous 30 minutes
Instructions:
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
  • Renal toxicity is dose related and cumulative and may be severe or fatal. Monitor renal function before and after each course of therapy. Mild proteinuria is one of the first signs of renal toxicity and may herald further deterioration of renal function.
fluorouracil 400 mg/m² Once daily intravenous 15 minutes
ondansetron 8 mg oral administration
Instructions:

EIGHT hours after chemotherapy OR before bed.
cyclIZINE 50 mg Three times daily oral administration
Instructions:

When required for nausea and/or vomiting.

  • Warning: may cause drowsiness.
  • Consider starting dose at 25 mg and increasing as tolerated/required.
  • The choice of rescue antiemetic may be substituted to reflect institutional policy or individual patient characteristics.
  • Note that domperidone is not recommended in combination with olanzapine and ondansetron due to potential risk of QT prolongation.
docusate sodium + sennoside B 2 Tablet(s) oral administration
Instructions:

At night when required for constipation.

  • Each tablet contains docusate sodium 50 mg + sennoside B 8 mg.
loperamide 2 mg oral administration
Instructions:
Take TWO capsules (=4 mg) at onset of loose bowel motions and a further ONE capsule (=2 mg) for every loose bowel motion (maximum of EIGHT capsules in 24 hours), or use as directed by oncologist or haematologist.

Day: 2

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONCE daily, regular daily dose. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
aprepitant * 80 mg oral administration
Instructions:
ONCE daily in the morning.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.
ondansetron 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to streptozocin infusion.
streptozocin 500 mg/m² Once daily intravenous 30 minutes
Instructions:
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
  • Renal toxicity is dose related and cumulative and may be severe or fatal. Monitor renal function before and after each course of therapy. Mild proteinuria is one of the first signs of renal toxicity and may herald further deterioration of renal function.
fluorouracil 400 mg/m² Once daily intravenous 15 minutes
ondansetron 8 mg oral administration
Instructions:

EIGHT hours after chemotherapy OR before bed.

Day: 3

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONCE daily, regular daily dose. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
aprepitant * 80 mg oral administration
Instructions:
ONCE daily in the morning.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.
ondansetron 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to streptozocin infusion.
streptozocin 500 mg/m² Once daily intravenous 30 minutes
Instructions:
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
  • Renal toxicity is dose related and cumulative and may be severe or fatal. Monitor renal function before and after each course of therapy. Mild proteinuria is one of the first signs of renal toxicity and may herald further deterioration of renal function.
fluorouracil 400 mg/m² Once daily intravenous 15 minutes
ondansetron 8 mg oral administration
Instructions:

EIGHT hours after chemotherapy OR before bed.

Day: 4

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONCE daily, regular daily dose. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
aprepitant * 80 mg oral administration
Instructions:
ONCE daily in the morning.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.
ondansetron 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to streptozocin infusion.
streptozocin 500 mg/m² Once daily intravenous 30 minutes
Instructions:
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
  • Renal toxicity is dose related and cumulative and may be severe or fatal. Monitor renal function before and after each course of therapy. Mild proteinuria is one of the first signs of renal toxicity and may herald further deterioration of renal function.
fluorouracil 400 mg/m² Once daily intravenous 15 minutes
ondansetron 8 mg oral administration
Instructions:

EIGHT hours after chemotherapy OR before bed.

Day: 5

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONCE daily, regular daily dose. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
aprepitant * 80 mg oral administration
Instructions:
ONCE daily in the morning.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.
ondansetron 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to streptozocin infusion.
streptozocin 500 mg/m² Once daily intravenous 30 minutes
Instructions:
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
  • Renal toxicity is dose related and cumulative and may be severe or fatal. Monitor renal function before and after each course of therapy. Mild proteinuria is one of the first signs of renal toxicity and may herald further deterioration of renal function.
fluorouracil 400 mg/m² Once daily intravenous 15 minutes
ondansetron 8 mg oral administration
Instructions:

EIGHT hours after chemotherapy OR before bed.

Day: 6

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONCE daily, regular daily dose. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

  • Dose and duration may be individualised at clinician’s discretion.

Day: 7

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONCE daily, regular daily dose. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

  • Dose and duration may be individualised at clinician’s discretion.

Supportive Care Factors

Factor Value
Constipation risk: laxatives are usually prescribed
Diarrhoea risk: Anti-diarrhoeals are usually prescribed with this treatment
Emetogenicity: High
Hydration: Routine hydration recommended

References

Lahner H, Mathew A, Klocker AL, et al. Streptozocin/5-fluorouracil chemotherapy of pancreatic neuroendocrine tumours in the era of targeted therapy. Endocrine. 2022 Jan;75(1):293-302. doi: 10.1007/s12020-021-02859-y. Epub 2021 Sep 4. , PMID: 34480724

Sun W, Lipsitz S, Catalano P, Mailliard JA, Haller DG; Eastern Cooperative Oncology Group. Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol. 2005 Aug 1;23(22):4897-904. doi: 10.1200/JCO.2005.03.616. , PMID: 16051944

Clewemar Antonodimitrakis P, Sundin A, Wassberg C, Granberg D, Skogseid B, Eriksson B. Streptozocin and 5-Fluorouracil for the Treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity. Neuroendocrinology. 2016;103(3-4):345-53. doi: 10.1159/000439086. Epub 2015 Aug 7., PMID: 26279284

Dilz LM, Denecke T, Steffen IG, Prasad V, von Weikersthal LF, Pape UF, Wiedenmann B, Pavel M. Streptozocin/5-fluorouracil chemotherapy is associated with durable response in patients with advanced pancreatic neuroendocrine tumours. Eur J Cancer. 2015 Jul;51(10):1253-62. doi: 10.1016/j.ejca.2015.04.005. Epub 2015 Apr 29., PMID: 25935542

National Comprehensive Cancer Network. Neuroendocrine and Adrenal Tumors. (Version 4. 2021). https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf Accessed 20 January, 2022.

National Comprehensive Cancer Network. Antiemesis. (Version 1. 2022). https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf Accessed 31 January 2022.

Teva Pharmaceuticals USA Inc. Zanosar Drug Label Information. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=15d161ed-9e7b-4c92-ba45-0556d2423e67 Accessed 31 January 2022.

* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.

s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.