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Non-Hodgkin lymphoma CHOEP14 (CYCLOPHOSPHamide DOXOrubicin vinCRISTine etoposide prednisolone)

Patients with lymphoma should be considered for inclusion into clinical trials. Link to ALLG website, ANZCTR website and Lymphoma Australia website.

This protocol is based on limited evidence; refer to the evidence section of this protocol for more information.

The anticancer drug(s) in this protocol may have been included in the ADDIKD guideline. Dose recommendations in kidney dysfunction have yet to be updated to align with the ADDIKD guideline. Recommendations will be updated once the individual protocol has been evaluated by the reference committee. For further information refer to the ADDIKD guideline. To assist with calculations, use the eviQ Estimated Glomerular Filtration Rate (eGFR) calculator.

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Cycle 1 to 6

Drug Dose Route Day
Prednisolone 100 mg ONCE a day PO 1 to 5
DOXOrubicin 50 mg/m2 IV 1
vinCRISTine 2 mg IV infusion 1
Etoposide * 100 mg/m2 IV infusion 1 to 3
CYCLOPHOSPHamide 750 mg/m2 IV infusion 1
Pegfilgrastim 6 mg Subcut 4

* Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg. Doses in this protocol are expressed as etoposide

Frequency:
14 days 
Cycles:
6 
Notes:

Consider the use of prephase prednisolone 100 mg PO daily for 5 to 7 days prior to Cycle 1.

Drug status:

Pegfilgrastim: (PBS authority)

All other drugs in this protocol are on the PBS general schedule

Prednisolone is available as 25 mg, 5 mg and 1 mg tablets

Cost:
~ $650 per cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au), MIMS Online and other sources. These costs are reviewed and updated on eviQ at 6 monthly intervals.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, 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
Prednisolone 100 mg (PO) ONCE a day on days 1 to 5. Take in the morning with food.
Palonosetron 0.25 mg (IV bolus) 30 minutes before chemotherapy
DOXOrubicin 50 mg/m2 (IV) over 5 to 15 minutes
vinCRISTine 2 mg (IV infusion) in 50 mL sodium chloride 0.9% over 5 to 10 minutes

via minibag
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% or glucose 5% over 30 to 60 minutes
CYCLOPHOSPHamide 750 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 2 and 3
Prednisolone 100 mg (PO) ONCE a day on days 1 to 5. Take in the morning with food.
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% or glucose 5% over 30 to 60 minutes
Day 4
Prednisolone 100 mg (PO) ONCE a day on days 1 to 5. Take in the morning with food.
Pegfilgrastim 6 mg (Subcut) Inject subcutaneously on day 4.
Day 5
Prednisolone 100 mg (PO) ONCE a day on days 1 to 5. Take in the morning with food.

  • Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg. Doses in this protocol are expressed as etoposide

Frequency:
14 days 
Cycles:
6 

Cycle 1 to 6

Drug Dose Route Day
Prednisolone 100 mg ONCE a day PO 1 to 5
DOXOrubicin 50 mg/m2 IV 1
vinCRISTine 2 mg IV infusion 1
Etoposide * 100 mg/m2 IV infusion 1 to 3
CYCLOPHOSPHamide 750 mg/m2 IV infusion 1
Pegfilgrastim 6 mg Subcut 4

* Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg. Doses in this protocol are expressed as etoposide

Frequency:
14 days 
Cycles:
6 
Notes:

Consider the use of prephase prednisolone 100 mg PO daily for 5 to 7 days prior to Cycle 1.

Drug status:

Pegfilgrastim: (PBS authority)

All other drugs in this protocol are on the PBS general schedule

Prednisolone is available as 25 mg, 5 mg and 1 mg tablets

Cost:
~ $650 per cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au), MIMS Online and other sources. These costs are reviewed and updated on eviQ at 6 monthly intervals.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, 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
Prednisolone 100 mg (PO) ONCE a day on days 1 to 5. Take in the morning with food.
Palonosetron 0.25 mg (IV bolus) 30 minutes before chemotherapy
DOXOrubicin 50 mg/m2 (IV) over 5 to 15 minutes
vinCRISTine 2 mg (IV infusion) in 50 mL sodium chloride 0.9% over 5 to 10 minutes

via minibag
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% or glucose 5% over 30 to 60 minutes
CYCLOPHOSPHamide 750 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 2 and 3
Prednisolone 100 mg (PO) ONCE a day on days 1 to 5. Take in the morning with food.
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% or glucose 5% over 30 to 60 minutes
Day 4
Prednisolone 100 mg (PO) ONCE a day on days 1 to 5. Take in the morning with food.
Pegfilgrastim 6 mg (Subcut) Inject subcutaneously on day 4.
Day 5
Prednisolone 100 mg (PO) ONCE a day on days 1 to 5. Take in the morning with food.

  • Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg. Doses in this protocol are expressed as etoposide

Frequency:
14 days 
Cycles:
6 
  • Peripheral T-cell lymphoma (PTCL), prior to autologous transplant
Safety alert vincristine administration

For safe administration of vincristine refer to the safety alert issued by the Australian Commission on Safety and Quality in Health Care
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
Hypersensitivity/infusion related reaction

High risk with etoposide.
Emetogenicity MODERATE

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

As a steroid has been included as part of this protocol, additional antiemetic steroids are not required.

For patients with a prior episode of chemotherapy induced nausea or vomiting, a NK1 receptor antagonist may be available on the PBS in combination with a 5HT3 antagonist and steroid.

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
Cumulative lifetime dose of anthracyclines

Cumulative doses should take into account all previous anthracyclines received during a patient’s lifetime (i.e. daunorubicin, doxorubicin, epirubicin, idarubicin and mitoxantrone). 

Criteria for reducing the total anthracycline cumulative lifetime dose include:

  • patient is elderly
  • prior mediastinal radiation
  • hypertensive cardiomegaly
  • concurrent therapy with high dose cyclophosphamide and some other cytotoxic drugs (e.g. bleomycin, dacarbazine, dactinomycin, etoposide, melphalan, mitomycin and vincristine).

Baseline clinical assessments include echocardiogram (ECHO) or gated heart pool scan (GHPS) and electrocardiogram (ECG) evaluation.

Patients with normal baseline cardiac function (left ventricular ejection fraction (LVEF) > 50%) and low risk patients require LVEF monitoring when greater than 70% of the anthracycline threshold is reached or if the patient displays symptoms of cardiac impairment. Post-treatment cardiac monitoring is recommended for patients who have received high levels of total cumulative doses of anthracyclines at the clinician's discretion.

Read more about cardiac toxicity associated with anthracyclines
Peripheral neuropathy

Assess prior to each treatment. Based on clinical findings, temporary omission, dose reduction or cessation of the vinca alkaloid may be indicated; review by medical officer before commencing treatment.

Read more about peripheral neuropathy

Link to chemotherapy-induced peripheral neuropathy screening tool
Constipation

Prescribe prophylactic laxatives to prevent constipation related to the use of vinca alkaloids.
Etoposide conversion factor

Note: Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg.
Doses in this protocol are expressed as etoposide.
Corticosteroids

Diabetic patients should monitor their blood glucose levels closely. To minimise gastric irritation, advise patient to take immediately after food. Consider the use of a H2 antagonist or proton pump inhibitor if appropriate.

Read more about acute short term effects from corticosteroids
Central nervous system (CNS) prophylaxis

Consider CNS relapse assessment in patients with high grade lymphoma. 

Read more about CNS prophylaxis in diffuse large cell lymphoma
Tumour lysis risk

Patients are at high risk of developing tumour lysis syndrome, prophylaxis is recommended.

Read more about the prevention and management of tumour lysis syndrome.
Pneumocystis jirovecii pneumonia (PJP) prophylaxis

­

Read more about prophylaxis of pneumocystis jiroveci (carinii) in cancer patients
Antiviral prophylaxis

­

Read more about antiviral prophylaxis drugs and doses
Antifungal prophylaxis ­

Read more about antifungal prophylaxis drugs and doses.
Biosimilar drug

Read more about biosimilar drugs on the Biosimilar Awareness Initiative page
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
Blood test

FBC at baseline and repeat prior to each cycle.
EUCs, LFTs, LDH and BSL at baseline and regularly throughout treatment 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.

Refer to the recommended schedule of vaccination for immunocompromised patients, as outlined in the Australian Immunisation Handbook.

Read more about COVID-19 vaccines and cancer.
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 foetal 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 effect of cancer treatment on fertility
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) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.
The dose recommendations in kidney dysfunction (i.e.renal impairment) displayed may not reflect those in the ADDIKD guideline and have been included for historical reference only. Recommendations will be updated once the individual protocol has been evaluated by the reference committee, with this version of the protocol then being archived. Clinicians are expected to refer to the ADDIKD guideline prior to prescribing in kidney dysfunction.
International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD).

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

Haematological toxicity
Dose modification is not generally indicated. Discuss with Haematologist. Consider lengthening time between cycles to 21 days if there is prolonged myelosuppression.
Renal impairment
Creatinine clearance (mL/min)
10 to 50 Reduce etoposide by 25%
less than 10 Reduce cyclophosphamide by 25% and etoposide by 50%
Hepatic impairment
Bilirubin (micromols/L)
20 to 50 Reduce doxorubicin by 50%
51 to 85 Reduce doxorubicin by 75%
greater than 85 Omit doxorubicin and etoposide

Note: Consider reducing vincristine dose for hepatic impairment. Omission of etoposide or dose modification may not be appropriate for patients with Haemophagocytic Lymphohistiocytosis (HLH) with hepatic impairment and physician discretion is required in this situation.

Peripheral neuropathy
Grade 2 Consider omitting vincristine

Drug interactions in eviQ protocols are under review and being updated to align with current literature. Further site-wide updates and changes will occur in due course. References & Disclaimer

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:  

Cyclophosphamide
  Interaction Clinical management
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Increased toxicity of cyclophosphamide possible due to increased conversion to active (and inactive) metabolites Avoid combination or monitor for cyclophosphamide toxicity
CYP3A4 inhibitors (e.g. aprepitant, azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.) Reduced efficacy of cyclophosphamide possible due to decreased conversion to active (and inactive) metabolites Avoid combination or monitor for decreased clinical response to cyclophosphamide
Amiodarone Possible additive pulmonary toxicity with high-dose cyclophosphamide (i.e. doses used prior to stem cell transplant; 60 mg/kg daily or 120 to 270 mg/kg over a few days) Avoid combination or monitor closely for pulmonary toxicity
Allopurinol, hydrochlorothiazide, indapamide Delayed effect. Increased risk of bone marrow depression; probably due to reduced clearance of active metabolites of cyclophosphamide Avoid combination, consider alternative antihypertensive therapy or monitor for myelosuppression
Ciclosporin Reduced efficacy of ciclosporin due to reduced serum concentration Monitor ciclosporin levels; adjust dosage as appropriate; monitor response to ciclosporin
Suxamethonium Prolonged apnoea due to marked and persistent inhibition of cholinesterase by cyclophosphamide Alert the anaesthetist if a patient has been treated with cyclophosphamide within ten days of planned general anaesthesia
Doxorubicin
  Interaction Clinical management
Cardiotoxic drugs (eg. bevacizumab, calcium channel blockers, propranolol, trastuzumab) Increased risk of doxorubicin-induced cardiotoxicity Avoid combination or monitor closely for cardiotoxicity
Cyclophosphamide Sensitises the heart to the cardiotoxic effects of doxorubicin; also, doxorubicin may exacerbate cyclophosphamide induced cystitis Monitor closely for cardiotoxicity and ensure adequate prophylaxis for haemorrhagic cystitis when combination is used
Glucosamine Reduced efficacy of doxorubicin (due to induction of glucose-regulated stress proteins resulting in decreased expression of topoisomerase II in vitro) The clinical effect of glucosamine taken orally is unknown. Avoid combination or monitor for decreased clinical response to doxorubicin
CYP2D6 inhibitors (e.g. SSRIs (esp. paroxetine), perhexiline, cinacalcet, doxepin, flecainide, quinine, terbinafine) Increased toxicity of doxorubicin possible due to reduced clearance Monitor for doxorubicin toxicity
CYP3A4 inhibitors (e.g. aprepitant, azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.) Increased toxicity of doxorubicin possible due to reduced clearance Monitor for doxorubicin toxicity
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John's wort etc.) Reduced efficacy of doxorubicin possible due to increased clearance Monitor for decreased clinical response to doxorubicin
Etoposide and Etoposide Phosphate
  Interaction Clinical management
CYP3A4 and P-gp inhibitors (e.g. amiodarone, aprepitant, azole-antifungals, ritonavir, lapatinib, nilotinib, sorafenib, macrolides, ciclosporin etc.) Increased toxicity of etoposide possible due to reduced clearance Avoid combination or monitor for etoposide toxicity
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Reduced efficacy of etoposide possible due to increased clearance Avoid combination or monitor for decreased clinical response to etoposide
Glucosamine Reduced efficacy of etoposide (due to induction of glucose-regulated stress proteins resulting in decreased expression of topoisomerase II) Avoid combination or monitor for decreased clinical response to etoposide
Grapefruit juice Reduced efficacy of oral etoposide possible due to possible alteration of P-gp mediated intestinal transport of etoposide Avoid combination or monitor for decreased clinical response to etoposide
Prednisolone
  Interaction Clinical management
Antidiabetic agents (e.g. insulin, glibenclamide, glicazide, metformin, pioglitazone, etc) The efficacy of antidiabetic agents may be decreased Use with caution and monitor blood glucose
Azole antifungals (e.g. fluconazole, itraconazole, ketoconazole, posaconazole) Increased toxicity of prednisolone possible due to reduced clearance Avoid combination or monitor for prednisolone toxicity
Oestrogens (e.g. oral contraceptives) Increased toxicity of prednisolone possible due to reduced clearance Avoid combination or monitor for prednisolone toxicity. Dose reduction of prednisolone may be required
Ritonavir Increased toxicity of prednisolone possible due to reduced clearance Avoid combination or monitor for prednisolone toxicity
Vincristine
  Interaction Clinical management
CYP3A4 and P-gp inhibitors (e.g. amiodarone, aprepitant, azole-antifungals, ritonavir, lapatinib, nilotinib, sorafenib, macrolides, ciclosporin, grapefruit juice etc.) Increased toxicity of vincristine possible due to reduced clearance Monitor for vincristine toxicity (esp. neurotoxicity, paralytic ileus)
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Reduced efficacy of vincristine possible due to increased clearance Monitor for decreased clinical response to vincristine
Mitomycin Acute shortness of breath and severe bronchospasm has occurred following use of vincristine in patients who had received mitomycin simultaneously or within 2 weeks Use combination with caution
Ototoxic drugs (e.g. cisplatin, aminoglycosides, frusemide, NSAIDs) Additive ototoxicity Avoid combination or perform regular audiometric testing
General
  Interaction Clinical management
Warfarin Anti-cancer drugs may alter the anticoagulant effect of warfarin. Monitor INR regularly and adjust warfarin dosage as appropriate; consider alternative anticoagulant.
Direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban, dabigatran

Interaction with both CYP3A4 and P-gp inhibitors /inducers.

DOAC and anti-cancer drug levels may both be altered, possibly leading to loss of efficacy or toxicity (i.e. increased bleeding).

Apixaban: avoid concurrent use with strong CYP3A4 and P‑gp inhibitors. If treating VTE, avoid use with strong CYP3A4 and P‑gp inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 and P‑gp  inhibitors.

Dabigatran: avoid combination with strong P‑gp inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
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
Vaccines Diminished response to vaccines and increased risk of infection with live vaccines. Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

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. 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 website for further information.

Day 1

Approximate treatment time: 3 hours

General patient assessment prior to each day of treatment.

Peripheral neuropathy assessment tool

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

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

  • weigh patient on each visit
  • urinalysis each visit

Hydration if prescribed

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

Prednisolone

  • administer orally ONCE a day on days 1 to 5
  • to be taken in the morning with or immediately after food

Note: if a dose is forgotten or vomited, contact treating team.

Doxorubicin

Administer doxorubicin (vesicant):
  • over 5 to 15 minutes
    • via a minibag OR
    • by IV bolus via a side port of a freely flowing IV infusion
  • ensure vein is patent and monitor for signs of extravasation throughout administration
  • flush with ~150 mL of sodium chloride 0.9%
  • potential for flare reaction during administration of doxorubicin (facial flushing and red streaking along the vein) stop infusion and exclude extravasation before continuing at a slower rate of infusion.

Although rare, cardiac arrhythmias may occur during or immediately after doxorubicin administration. If sudden onset of dyspnoea, palpitations or irregular pulse occurs, stop administration immediately and obtain urgent medical officer review.

Vincristine

Administer vincristine (vesicant)
  • via a minibag over 5 to 10 minutes
  • ensure vein is patent and monitor for signs of extravasation throughout administration
  • flush with ~150 mL of sodium chloride 0.9%.

Etoposide

Administer etoposide (irritant):
  • via IV infusion over 30 to 60 minutes
  • rapid infusion may cause hypotension
  • observe for hypersensitivity
  • flush with ~ 100 mL sodium chloride 0.9%
  • if using etoposide phosphate administer in ~ 50 mL sodium chloride 0.9% or glucose 5% over ~15 minutes.
Stop infusion at first sign of reaction:
  • if symptoms are mild and resolve when infusion is stopped, consider recommencing infusion after review by medical officer at a slower rate.
  • for severe reactions seek medical assistance immediately and do not restart infusion.

Cyclophosphamide

Administer cyclophosphamide:
  • via IV infusion over 30 to 60 minutes
  • flush with ~ 50 mL of sodium chloride 0.9%
  • rapid infusion can cause dizziness, rhinitis, nausea and perioral numbness. If symptoms develop, slow infusion rate.

Remove IV cannula and/or deaccess TIVAD or CVAD. 

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

Days 2 and 3

Approximate treatment time: 90 minutes

General patient assessment prior to each treatment.

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

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

  • weigh patient on each visit
  • urinalysis each visit

Hydration if prescribed

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

Prednisolone

  • administer orally ONCE a day on days 1 to 5
  • to be taken in the morning with or immediately after food

Note: if a dose is forgotten or vomited, contact treating team.

Etoposide

Administer etoposide (irritant):
  • via IV infusion over 30 to 60 minutes
  • rapid infusion may cause hypotension
  • observe for hypersensitivity
  • flush with ~ 100 mL sodium chloride 0.9%
  • if using etoposide phosphate administer in ~ 50 mL sodium chloride 0.9% or glucose 5% over ~15 minutes.
Stop infusion at first sign of reaction:
  • if symptoms are mild and resolve when infusion is stopped, consider recommencing infusion after review by medical officer at a slower rate.
  • for severe reactions seek medical assistance immediately and do not restart infusion.

Remove IV cannula and/or deaccess TIVAD or CVAD. 

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

Day 4

Prednisolone

  • administer orally ONCE a day on days 1 to 5
  • to be taken in the morning with or immediately after food

Note: if a dose is forgotten or vomited, contact treating team.

Pegfilgrastim

  • administer subcutaneously on day 4; or ensure arrangements have been made for administration

Discharge information

Prednisolone tablets
  • Prednisolone tablets with written instructions on how to take them.
Antiemetics
  • Antiemetics as prescribed.
Laxatives
  • Ensure patient has prophylactic laxatives.
Growth factor support
  • Arrangements for administration if prescribed.
Prophylaxis medications
  • Prophylaxis medications (if prescribed) i.e. tumour lysis prophylaxis, PJP prophylaxis, antifungals, antivirals.
Patient information
  • Ensure patient receives 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)
Hypersensitivity reaction

Anaphylaxis and infusion related reactions can occur with this treatment.

Read more about hypersensitivity reaction 
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting
Bone pain

Bone pain, usually in the lower back or pelvis, associated with G-CSF.
Extravasation, tissue or vein injury

The unintentional instillation or leakage of a drug or substance out of a blood vessel into surrounding tissue. This has the potential to cause damage to affected tissue.

Read more about extravasation management
Flare reaction

Anthracycline flare reaction is caused by a localised allergic reaction. It is characterised by erythematous vein streaking, urticaria and pruritus which may occur during drug administration and is often associated with too rapid an infusion. Extravasation must be ruled out if flare occurs.
Headache
Red-orange discolouration of urine

Pink/red/orange discolouration of the urine. This can last for up to 48 hours after some anthracycline drugs.
Taste and smell alteration

Read more about taste and smell changes

Early (onset days to weeks)
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
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Constipation
Diarrhoea

Read more about treatment induced diarrhoea
Fatigue

Read more about fatigue
Haemorrhagic cystitis

An inflammatory process, characterised by diffuse mucosal inflammation with haemorrhage involving the entire bladder. Patients are at risk following treatment with cyclophosphamide, ifosfamide and radiation therapy. 

Read more about haemorrhagic cystitis
Oral mucositis

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following chemotherapy, 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
Peripheral neuropathy

Typically symmetrical sensory neuropathy, affecting the fingers and toes, sometimes progressing to the hands and feet.  It is associated with several classes of anti-cancer drugs. These include taxanes, platinum-based compounds, vinca alkaloids and some drugs used to treat multiple myeloma.

Read more about peripheral neuropathy
Side effects of corticosteroids

Insomnia, oedema, increased risk of infection e.g. oral thrush, gastric irritation, worsening of peptic ulcer disease, increased blood sugar levels, loss of diabetic control, mood and behavioural changes - including anxiety, euphoria, depression, mood swings, increased appetite and weight gain, osteoporosis and fractures (long term use), bruising and skin fragility are associated with corticosteroid use.
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

Late (onset weeks to months)
Alopecia

Hair loss may occur from all parts of the body. 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
Anaemia

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

Read more about anaemia

Delayed (onset months to years)
Cardiotoxicity

Anthracyclines are the most frequently implicated anti-cancer drugs associated with cardiotoxicity, which typically manifests as a reduction in left ventricular ejection fraction (LVEF), cardiomyopathy, or symptomatic CHF. Anthracycline induced cardiotoxicity has been categorised into acute, early-onset chronic progressive and late-onset chronic progressive and is usually not reversible. The risk of clinical cardiotoxicity increases with a number of risk factors including higher total cumulative doses. 

Read more about cardiac toxicity associated with anthracyclines
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

Expected outcomes for patients with Peripheral T-Cell Lymphoma (PTCL) is largely based on 2 large retrospective series: the International T-Cell Project (ITCP) and the British Columbia Cancer Agency (BCCA) series, which reported outcomes on 1314 cases and 199 cases, respectively.rr In the ITCP, >85% of patients received CHOP-based therapy. The 5-year FFS for PTCL-NOS, angioimmunoblastic T-Cell lymphoma (AITL), and ALK-negative anaplastic large cell lymphoma (ALCL) were only 20%, 18%, and 36%, respectively. Similar outcomes were observed in the BCCA series with 5-year progression-free survival (PFS) of 29%, 13%, and 28% for PTCL-NOS, AITL, and ALCL, respectively.r

There is no currently agreed on standard frontline treatment or approach for PTCL. In a phase 2 study evaluating CHOP induction therapy followed by ASCT for untreated PTCL, the overall response rate (ORR) to CHOP was 79% with a complete response (CR) rate of 39%.r

A small phase 3 study from the GOELAMS (Groupe Ouest Est d'Etude des Leucémies aiguës et Autres Maladies du Sang) group of CHOP vs etoposide, ifosfamide, cisplatin alternating with adriamycin, bleomycin, vinblastine, and dacarbazine showed no difference in outcome for the 2 arms and resulted in an ORR of 70% and a CR rate of 35% with CHOP.r

A search of the literature found limited evidence to support the use of CHOEP14 for the treatment of peripheral T-cell lymphoma. The expert reference panel supported publication of the protocol on the basis of the information summarised below. The committee was most strongly influenced by the retrospective analysis of patients treated in studies of the German High Grade Non-Hodgkin Lymphoma Study Group reported by Schmitz et alr and also by the large prospective phase II study reported by d'Amore et al.r

Source Study & Year Published Supports Use Is the dose and regimen consistent with the protocol? Comments
Retrospective series Schmitz et al. 2010 Yes Yes -
Phase II trials d'Amore et al. 2012 Yes Yes -
Case series N/A N/A N/A -
Observational studies N/A N/A N/A -
Guidelines Date published/revised Supports Use Is the dose and regimen consistent with the protocol? Comments
NCCN Version 1.2016 Yes N/A -
BCCA N/A N/A Yes -
CCO N/A N/A Yes -

Efficacy

The addition of etoposide to CHOP (CHOEP) has been studied in an attempt to improve on the CR and FFS rates achieved with CHOP. The German high-grade non-Hodgkin lymphoma study group analyzed the subset of patients with PTCL treated on 7 different prospective phase 2 or phase 3 protocols.r Of 320 patients with PTCL enrolled in these studies, most had 1 of 4 of the major subtypes of PTCL: 78 patients with ALK-positive ALCL, 113 patients with ALK-negative ALCL, 70 patients with PTCL-NOS, and 28 patients with AITL. The authors found that younger patients (<60 years old) with normal lactate dehydrogenase (LDH) had a significant improvement in outcome if they received CHOP plus etoposide compared with CHOP alone, with 3-year event-free survival (EFS) of 75.4% vs 51%, although no difference in overall survival (OS) was observed. The benefits were greatest in the more favourable ALK-positive ALCL subtype, but there was a trend toward improved EFS in favour of CHOP plus etoposide in the other subsets as well (P = 0.057).

The Nordic group have conducted a phase 2 prospective study of CHOEP induction followed by upfront stem cell transplantation for PTCL.r In this phase 2 study, patients received bi-weekly CHOEP-14 followed by ASCT for the responders. The ORR to CHOEP was 82% with a CR rate of 51%. The highest OS and PFS occurred in patients with ALCL (5 years OS 70%; PFS 61%). AILT and PTCL-NOS had an OS at 5 years of 52% and 47% and PFS of 49% and 38% respectively.r Elderly patients received an induction treatment consisting of biweekly CHOP i.e. without etoposide. The 5 year OS and PFS for this subcohort were 45% and 34% respectively. The corresponding values for CHOEP treated patients aged 55 to 60 years were similar however at 40% and 39%.r Adding etoposide to CHOP represents a reasonable approach, particularly in select groups as long as it can be given without significant excess toxicity.

Toxicity

In elderly patients, the addition of etoposide added significant toxicity. In the Nordic study of biweekly CHOEP pretransplantation grades 3 to 4 haematologic toxicity were seen in 86% of patients and grades 3 to 4 non haematologic toxicities were recorded in 72 patients (45%). Infectious complications were the most adverse event (n=59, 37%), followed by mucositis (n=7, 4% and GI toxicity (n=6, 4%).r

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Version 3

Date Summary of changes
22/09/2020 Biosimilar drug added to clinical information. Version number changed to v.3
21/01/2022 Dose modifications note updated.
24/01/2022 Pulmonary toxicity added to side effects.

Version 2

Date Summary of changes
14/01/2016 New protocol approved and published on eviQ.
31/05/2017 Transferred to new eviQ website. Version number change to v.2.Other changes include:
  • diluent volume of vincristine changed from ‘50 to 100 mL’ to ‘50 mL’ as per Australian Injectable Handbook Sixth Edition.
25/05/2018 Reviewed by Haematology Reference Committee with no significant changes, review in 2 years
13/09/2019 Reviewed by Haematology Reference Committee, no changes made. Review in 5 years.
10/10/2019 Clinical information updated with PBS expanded indications for G-CSF. 
27/03/2020 Reviewed by Haematology Reference Committee with no significant changes, review in 4 years

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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31 Mar 2023