Acute Oncology Guidelines
- Prevention and optimal control of nausea and vomiting. Poor control may lead to delayed emesis within first treatment cycle and emesis with subsequent cycles.
- For combination regimes, choose an antiemetic according to the SACT agent with the greatest degree of risk (See Table 4 & 5 for agent classification). In addition to SACT agent, the following patient factors should be considered (Table 1).
- If there are two drugs of the same emetic class being used or a very susceptible patient then the anti-emetic regime of the next higher class should be considered.
- ACUTE symptoms – occur within 24 hours of last SACT dose (5HT3 pathways appear to dominate).
- DELAYED symptoms – 24 hours to 7 days of last SACT dose.
- Rescue anti-emetics should be given to patients to use “as required” for poorly controlled symptoms. If nausea & vomiting (N&V) controlled, consider regular rather than prn dosing and choice of any additional agents should be based on assessment of appropriate administration route and disease related issues e.g. brain metastases, electrolyte disturbances, opioids, infection, tumour infiltration of bowel or gastric obstruction. The chosen anti-emetic should not aggravate symptoms e.g. metoclopramide and gastric obstruction, 5HT3 antagonist and constipation.
- Anticipatory nausea - use the most active antiemetic appropriate for the SACT being administered to prevent acute or delayed emesis. Antiemetics should be used with initial cycle rather than assessing response. Consider lorazepam given orally on the night before and the morning of chemotherapy.
- ADMINISTRATION NOTE: Where prescribed intravenously, dexamethasone should be administered slowly (bolus over several minutes or infused over 15 – 30 minutes). If required intravenously, 5HT3 antagonists (granisetron or ondansetron) should be administered as an infusion over 15 minutes and not bolused. Note that concurrent administration of steroids can enhance the efficacy of 5HT3 antagonists.
Nausea and vomiting
Warning
Anti-emetic guidance for systemic anti cancer therapy (SACT) (S\Tox\15)
Emesis is a well recognised side effect associated with the use of systemic anti-cancer therapy (SACT). These guidelines are intended to provide guidance on the use of anti-emetics as prophylaxis and treatment of nausea and vomiting associated with use of SACT.
For guidance on use of anti-emetics during radiotherapy, refer to the anti-emetic guideline for radiotherapy treatment.
| Higher risk | Lower risk |
|
Previous exposure to SACT Younger patients (<50 years) Females (especially if history of sickness in pregnancy) Anxiety Travel or anaesthetic sickness |
History of alcohol excess Smoker |
| Regime type |
Pre-medication (give orals > 30 mins pre chemo) |
Oral anti-emetics to take home | Rescue anti-emetics |
|
High risk cisplatin : ≥ 60mg/m2 single day or multiple consecutive day cisplatin regimens or combined with other high risk agents |
A Akynzeo® (netupitant 300mg & palonosetron 0.5mg) 1 capsule (1 hour pre chemo) & dexamethasone 12mg IV |
Dexamethasone 4mg BD D2-4 Metoclopramide 10mg TDS for up to 5 days and then prn : additional information ECC metoclopramide statement |
|
|
B (For use when patients unable to take oral medication only) Fosaprepitant 150mg IV & dexamethasone 12mg IV & granisetron 2mg IV |
Dexamethasone 4mg BD D2-4 Granisetron 1mg OD D2-4 Metoclopramide 10mg TDS for up to 5 days and then prn: additional information ECC metoclopramide statement |
|
|
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High risk SACT (Risk in >90% patients. Lasts 2 days after last dose of SACT) Anthracycline/cyclophosphamide containing regimens to be considered as high risk |
Dexamethasone 16mg IV* & Granisetron 2mg oral day 1 For multiple consecutive day regimens subsequent days anti-emetics should be considered based upon risk of SACT drugs being given |
Dexamethasone 4mg BD D2-4 Granisetron 1mg OD D2-4.( 2mg for anthracycline/ cyclophos containing regimens)** Metoclopramide 10mg TDS for up to 5 days and then prn |
*In aprepitant containing regimens, IV dexamethasone dose is reduced to 12mg **(For multiple consecutive day regimens patients may have completed TTO course during treatment and not require to take anti-emetics home) |
|
Moderate Risk – delayed emesis common (Risk in 30-90% patients. Lasts 2 days after last dose of SACT)
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Dexamethasone 10mg oral Granisetron 2mg oral
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*Dexamethasone 4mg BD D2-4 oral Granisetron 1mg OD D2-4 oral Metoclopramide 10mg TDS for up to 5 days
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*Patients with grade 0 nausea / vomiting, consider reducing dexamethasone to 2mg BD D2-4 with subsequent treatment. If grade 0 nausea /vomiting on reduced dose, consider discontinuing TTO dexamethasone Consider regular prochlorperazine if vomiting. Consider a reducing course of dexamethasone (e.g 4mg BD 3/7, 2mg BD 2/7, 2mg od 2/7 and stop instead of 4mg BD D2-4). +/- lorazepam 0.5 to 1mg SL 8 hrly prn if anxious / anticipatory nausea. Consider addition of a PPI if dyspepsia contributing to nausea Switch oral dexamethasone pre-med to IV route |
|
Moderate risk – delayed emesis uncommon |
Dexamethasone 10mg oral Granisetron 1mg oral
|
Metoclopramide 10mg TDS prn |
Dexamethasone 4mg BD D2-4 if delayed emesis last cycle Add granisetron 1mg OD D2-4 if required |
|
Low risk Risk in 10-30% patients
|
Either granisetron 1mg oral or dexamethasone 10mg oral if required (as per the MPC or tumour group team decision) |
Nil |
Consider metoclopramide 10mg tds prn Consider addition of dexamethasone 4mg BD 3/7 Consider addition of granisetron 1mg oral pre-medication if failed first line anti-emetics |
|
Minimal risk Risk in < 10% patients
|
No pre med required unless patient specific factors dictate |
None |
|
| High |
Moderate (delayed emesis common – may last up to 4 days) |
Moderate (delayed emesis uncommon) |
Low
|
Minimal |
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Busulphan (high dose) Carmustine Cisplatin: high risk cisplatin : ≥ 60mg/m2 single day or multiple consecutive day cisplatin regimens or combined with other high risk agents Cyclophosphamide (>1500mg/m2) Cyclophosphamide (< 1500mg/m2 if paired with an anthracycline) Dacarbazine Dactinomycin Doxorubicin > 60mg/m2 Epirubicin > 90mg/m2 Ifosfamide > 10g/ m2 Methotrexate - high dose (>1.5g/m2) Streptozocin |
Arsenic trioxide Azacitidine Bendamustine Busulphan (low dose) Carboplatin Clofarabine Cyclophosphamide<1500mg/m2 Cytarabine >1000mg/m2 Daunorubicin Doxorubicin<50mg/m2 Epirubicin <90mg/ m2 Idarubicin Ifosfamide <10g/ m2 Irinotecan Melphalan Oxaliplatin Thiotepa Trabectadin |
Inotuzumab Mitoxantrone Raltitrexed Topotecan Vinflunine |
Avelumab Blinatumomab Bortezomib Brentuximab vendotin Cabazitaxel Carfilzomib Catunaxumab Cytarabine<1000mg/ m2 Daratumumab Docetaxel Epirubicin - weekly Eribulin Etoposide Fluorouracil (5-FU) |
Gemcitabine Liposomal doxorubicin Methotrexate (<1.5g/m2) Mitomycin Mitoxantrone Paclitaxel & Paclitaxel Albumin Panitumumab Pentostatin Pemetrexed Pertuzumab Temsirolimus Trastuzumab emtansine Vinflunine |
Aflibercept Alemtuzumab Bevacizumab Bleomycin Cetuximab Cladribine Fludarabine Iplimumab Nelarabine Nivolumab Obinutuzumab Ofatumumab Pembrolizumab Pixantrone Rituximab Trastuzumab Vinblastine Vincristine Vinorelbine
|
| High | Moderate | Low | Minimal | ||||
| Procarbazine |
Bosutinib Cabozantinib Ceritinib Crizotinib Imatinib Lomustine Lonsurf Lenvatinib Midostaurin Nintedanib Temozolomide Vinorelbine |
Afatinib Axitinib Bexarotene Capecitabine Cyclophosphamide Cobimetinib Dabrafenib Etoposide Everolimus Fludarabine Ibrutinib |
Idelalisib Ixazomib Lapatinib Lenalidomide Mercaptopurine Niraparib Olaparib Palbociclib Panobinostat Ponatinib Regorafenib |
Ribociclib Sunitunib Temsirolimus Teysuno Thalidomide Topotecan Trametinib Vandetanib Vemurafenib Venetoclax |
Chlorambucil Dasatinib Erlotinib Enzalutamide Gefitinib Imatinib |
Hydroxycarbamide Melphalan Methotrexate Nilotinib Osimertinib Pazopinib |
Pomalidomide Ruxolitinib Sorafenib Tioguanine Ruxolitinib Vemurafanib Vismodegib |
| Anti-emetic | Parenteral dose | Oral dose | Prescribing notes |
|
Akynzeo (netupitant 300mg & palonosetron 0.5mg) |
N/A |
1 capsule single dose (300mg/0.5mg) 1 |
Administer 1 hour before cisplatin containing HEC. Caution in moderate / severe hepatic impairment Multiple drug interactions –see additional prescribing notes in table 7. Do not use in patients with SABO, switch to aprepitant and metoclopramide |
| Aprepitant | N/A |
125mg D1 80mg OD D2&3 |
Caution in mod / severe hepatic impairment Multiple interactions – see Additional prescribing notes Administer day 1 dose 1 hour before treatment |
| Cyclizine | 25-50mg 8 hourly IV/SC or 100-150mg CSCI pump over 24 hours | 50mg TDS |
Antimuscarinic side effects (dry mouth, blurred vision, constipation, hypotension and confusion. Slows peristalsis in GI tract. Useful if nausea lingering after first three days and metoclopramide not fully controlling. Caution in epilepsy. |
| Dexamethasone | 8-20mg IV pre-SACT |
8-20mg pre-SACT 2-4mg BD post-SACT |
May cause perineal discomfort if given by rapid IV bolus. In practice doses > 8mg should be given as an infusion over 15 mins. May induce / unmask/ destabilise diabetes – advise patients of symptoms of thirst / increased diuresis, increase BM monitoring in patients with diabetes as per ECC guidelines. May cause dyspepsia when used at high dose for prolonged course - consider PPI prophylaxis as per ECC policy. |
| Domperidone | N/A | 10mg TDS Suppositories and oral liquid available |
Note not preferred choice anti-emetic. Due to MHRA advice the use of domperidone should now be reserved for treatment of nausea / vomiting. It is not a preferred option. Due to the risk of sudden cardiac death in patients >60 with prolonged QT interval it should not be used in patients with identifiable risk factors and is contra-indicated in patients with underlying cardiac conditions, severe hepatic impairment, and in patients receiving other QT prolonging medicines or potent CYP3A4 inhibitors (e.g. itraconazole, fluconazole & clarithromycin). Restrict use to a maximum of 7 days. Consider baseline ECG if prescribing. The MHRA recommends use at the lowest possible dose for the shortest possible duration (max of 30mg per day). |
| Fosaprepitant | 150mg IV infusion over 20-30mins | N/A |
For patients unable to swallow oral NKI (akynzeo or aprepitant) Drug should be prepared on ward and administered as a 1mg/ml solution using method below:
|
| Granisetron | 1-2mg IV |
1-2mg OD. Can be used BD if OD dosing is ineffective. Sancuso® patch (32mg over 7 days). 1 patch applied 24–48 hours prior to SACT and to remain in place for a max of 7 days. |
May reduce lower bowel motility, patients with signs of sub-acute intestinal obstruction should be monitored following administration. As for other 5-HT3 antagonists, ECG changes including QT interval prolongation have been reported. Therefore, caution should be exercised in patients with cardiac rhythm or conduction disturbances, in patients using other medications that prolong QT interval (see Table 7), in patients treated with anti-arrhythmic agents or beta-adrenergic blocking agents and in patients with significant electrolyte disturbances (low potassium, magnesium or calcium). Concomitant use of cardio-toxic drugs (e.g. anthracyclines) may increase risk of arrhythmias. Common side effects: headache and constipation - consider laxatives, caution in patients with history of migraines. Consider granisetron patch for patients on multi-drug regimens where patients have swallowing difficulties. For any other indication MMC approval is required. Apply patch to a dry hairless area on the outer part of the upper arm. Patch could also be applied to the abdomen if arm is not possible. Patches should not be cut into pieces. Showering / bathing is permitted with the patch but patients should avoid direct heat / saunas. The patch should be covered by clothing and protected from direct natural or artificial sunlight for duration of wear and area protected for or up to 10 days after removal. |
| Levomepromazine |
5–25mg CSCI over 24 hours or 2.5mg SC injection 8-12hrly PRN |
N/A | S/C administration can be used for patients admitted with N&V. Use low doses in first instance to avoid sedation and hypotension. Avoid in liver dysfunction. Rare Reports of QT prolongation therefore care in patients with low potassium, calcium and magnesium levels and other drugs known to prolong QT interval |
| Lorazepam | 0.5–1mg IV up to TDS | 0.5–1mg up to TDS (sublingual) | Useful for patients who are anxious or who experience anticipatory nausea and vomiting |
| Metoclporamide | 5-10mg IM or IV 6-8 hourly (max 30mg in 24 hours) |
10mg TDS or 6 hourly prn Max of 3 doses in 24hrs (oral liquid available) |
The EMEA issued advice on use of metoclopramide in 2013 (ECC metoclopramide statement) restricting the dose and duration of use of the medicine to minimise the known risks of potentially serious neurological SE’s. Metoclopramide is associated with agitation and extra-pyramidal symptoms particularly in young females, in addition prolonged use may lead to neurological side effects in elderly patients in particular. Caution is advised in patients with parkinsons disease and taking concurrent neuroleptics. Bowel transit time can be reduced and it is contra-indicated in GI obstruction. The recommended single dose is 10 mg, repeated up to three times daily. The max recommended daily dose is 30 mg or 0.5mg/kg body weight. The max duration of regular treatment is 5 days, after which it can be taken as required. Regular use for longer than 5 days can be considered in patients who remain poorly controlled and are without risk factors at the prescriber’s discretion. |
| Ondansetron |
8-16 mg IV infusion (infuse over a minimum of 15 mins) Max dose IV=16mg; (in patients over 75 yrs, max dose IV=8mg) |
8mg BD (usual dose) Dose range 4-8mg up to TDS # |
Repeat IV doses should be given no less than 4 hrs apart. Administer with caution to patients who have or may develop prolongation of QTc.(see above for information beside granisetron). Ondansetron is known to increase large bowel transit time, patients with signs of sub-acute intestinal obstruction should be monitored following administration. Interactions: Potent inducers of CYP3A4 such as phenytoin, carbamazepine, and rifampicin, may increase the oral clearance of ondansetron and decrease ondansetron blood concentrations. Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol. # Melts formulation available for patients unable to swallow tablets – useful alternative 5HT3 antagonist for this situation. |
| Olanzapine | N/A |
5-10mg once daily (usually at night) 3rd line treatment option |
Adults who experience nausea or vomiting despite optimal prophylaxis should be offered olanzapine in addition to continuing the standard antiemetic regimen. 5-10mg pre-SACT then 5-10mg OD for 3 days following SACT. Available as tablets or orodispersible tablets for patients unable to swallow tablets. Causes drowsiness – caution with driving. Caution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc interval. May be pro-epileptogenic so should be used with caution with patients with difficult to control seizures. |
| Palonosetron |
250mcg STAT (no additional 5HT3 given) |
500mcg (1 capsule) PO approximately one hour prior to SACT. (preferential to IV dosing) |
Only for patients in whom steroids are C/I or compliance is in doubt. For other indications MMC approval is required. Risk of QTc prolongation as for other 5HTs antagonists (refer to granisetron cautions). May increase large bowel transit time therefore monitor in patients with constipation or potential SABO. Capsules contain sorbitol and lecithin derived from soya therefore patients with known sensitivity to soya or peanuts should be monitored closely for hypersensitivity reactions. Evidence (ASCO guidelines) suggests palonosetron is superior to ondansetron or granisetron during period of 24–120 hours post SACT but non-significant difference in first 24 hours therefore good if delayed emesis a particular problem. |
| Prochlorperazine |
5–10mg 2–3 times a day Deep IM 12.5mg if required |
5-10mg 2-3 times daily or Buccastem® 3-6mg BD |
May cause drowsiness. Avoid in liver or renal dysfunction, parkinsons disease, cardiac failure and hypothyroidism. Buccal preparation (Buccastem®) useful for the vomiting patient as absorbed from the oral mucosa. Place tablet between upper lip and gum and leave to dissolve. |
| Drug | Interaction |
| Warfarin | Decreased anti-coagulation effect. Monitor closely during and for 14 days after each 3 day course |
| Midazolam/dexamethasone | Increased plasma concentrations (N.B. dex doses already adjusted in table in combination with Akynzeo (netupitant & palonosetron)/fosaprepitant) and aprepitant) |
| Rifampicin, phenytoin, carbamazepine, phenobarbital | Decreased Akynzeo (netupitant & palonosetron)/fosaprepitant/aprepitant levels (possibly) |
|
Ketoconazole, clarithromycin, ritonavir. Concomitant use with St Johns Wort or pimozide |
Increased Akynzeo (netupitant & palonosetron)/fosaprepitant/aprepitant levels (possibly) |
| Docetaxel and etoposide | Increased toxicity of SACT |
| Hormonal contraceptives | Efficacy of contraceptives may be reduced during and for 28 days after administration of Akynzeo (netupitant & palonosetron)/fosaprepitant/aprepitant. Alternative or back-up methods of contraception should be used during treatment with Akynzeo (netupitant & palonosetron)/fosaprepitant/aprepitant and for 2 months following the last dose. |
| SSRIs and NSRIs | Some reports of serotonin syndrome with combination use. |
|
Amiodarone, chlorpromazine, citalopram, clarithromycin, erythromycin, fluconazole, haloperidol, methadone, octreotide, salmeterol, sotalol, tamoxifen, venlafaxine. (This list is not exhaustive, a useful website for additional info is http://www.qtdrugs.org/ Refer to NHS Lothian information on ‘Drug induced QT interval prolongation’ (only accessible when connected to intranet) |
- Summary of Product Characteristics, various drugs, www.medicines.org.uk
- FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron, safety announcement 29th June 2012. www.fda.gov/Drugs/DrugSafety/ucm310190.htm
- ESMO/MASCC Guidelines Working Group, 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients Basch et al, Antiemetics; American Society of Clinical Oncology Clinical Practice Guideline Update, ASCO Guidelines, April 2011. Annals of Oncology 27 (supplement 5) 119-133, 2016
- Medicines information enquiry, QT interval prolongation, personal communication fromTracy Duff, 6th July 2012
- NCCN , National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology – Antiemesis, July 2011
- EMA Pharmacovigilance working group. Monthly report Nov 2011(EMA/CHMP/PhVWP/845939/2011) Domperidone risk of cardiac disorders. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/10/WC500117061.pdf