Treatment schedule Treatment schedule
- Overview
- Detail
Cycle 1 to 6
| Drug | Dose | Route | Day |
|---|---|---|---|
| Prednisolone | 100 mg ONCE a day | PO | 1 to 5 |
| DOXOrubicin | 50 mg/m2 | IV | 1 |
| CYCLOPHOSPHamide | 750 mg/m2 | IV infusion | 1 |
| Brentuximab vedotin | 1.8 mg/kg (Cap dose at 180 mg) | IV infusion | 1 |
- Frequency:
- 21 days
- Cycles:
- 6to 8 unless disease progression or unacceptable toxicity occurs.
- Notes:
- G-CSF may be usedat the discretion of the treating clinician
- Drug status:
Brentuximabvedotin(PBS authority)
All other drugs in this protocol are on the PBS general schedule
Prednisolone is available as 1 mg, 5 mg and 25 mg tablets
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 scheduleare based upon recommendations from national and internationalguidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here forrecommended doses of alternative antiemetics.
Cycle 1 to 6
| Day 1 | ||
|---|---|---|
| Palonosetron | 0.25 mg (IV bolus) | 30 minutes before chemotherapy |
| Prednisolone | 100 mg (PO) | ONCE a day on days 1 to 5. Take in the morning with food. |
| DOXOrubicin | 50 mg/m2 (IV) | over 5 to 15 minutes |
| CYCLOPHOSPHamide | 750 mg/m2 (IV infusion) | in 500 mL sodium chloride 0.9% over 30 to 60 minutes |
| Brentuximab vedotin | 1.8 mg/kg (IV infusion) (Cap dose at 180 mg) | in 150 mL sodium chloride 0.9% over 30 minutes |
| Day 2 to 5 | ||
|---|---|---|
| Prednisolone | 100 mg (PO) | ONCE a day on days 1 to 5. Take in the morning with food. |
Notes:
- G-CSF may be usedat the discretion of the treating clinician
- Frequency:
- 21 days
- Cycles:
- 6to 8 unless disease progression or unacceptable toxicity occurs.
Treatment schedule - Overview
Cycle 1 to 6
| Drug | Dose | Route | Day |
|---|---|---|---|
| Prednisolone | 100 mg ONCE a day | PO | 1 to 5 |
| DOXOrubicin | 50 mg/m2 | IV | 1 |
| CYCLOPHOSPHamide | 750 mg/m2 | IV infusion | 1 |
| Brentuximab vedotin | 1.8 mg/kg (Cap dose at 180 mg) | IV infusion | 1 |
- Frequency:
- 21 days
- Cycles:
- 6to 8 unless disease progression or unacceptable toxicity occurs.
- Notes:
- G-CSF may be usedat the discretion of the treating clinician
- Drug status:
Brentuximabvedotin(PBS authority)
All other drugs in this protocol are on the PBS general schedule
Prednisolone is available as 1 mg, 5 mg and 25 mg tablets
Treatment schedule - Detail
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 scheduleare based upon recommendations from national and internationalguidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here forrecommended doses of alternative antiemetics.
Cycle 1 to 6
| Day 1 | ||
|---|---|---|
| Palonosetron | 0.25 mg (IV bolus) | 30 minutes before chemotherapy |
| Prednisolone | 100 mg (PO) | ONCE a day on days 1 to 5. Take in the morning with food. |
| DOXOrubicin | 50 mg/m2 (IV) | over 5 to 15 minutes |
| CYCLOPHOSPHamide | 750 mg/m2 (IV infusion) | in 500 mL sodium chloride 0.9% over 30 to 60 minutes |
| Brentuximab vedotin | 1.8 mg/kg (IV infusion) (Cap dose at 180 mg) | in 150 mL sodium chloride 0.9% over 30 minutes |
| Day 2 to 5 | ||
|---|---|---|
| Prednisolone | 100 mg (PO) | ONCE a day on days 1 to 5. Take in the morning with food. |
Notes:
- G-CSF may be usedat the discretion of the treating clinician
- Frequency:
- 21 days
- Cycles:
- 6to 8 unless disease progression or unacceptable toxicity occurs.
Indications and patient population
- Previously untreated CD30+ peripheral T-cell lymphoma
Clinical information
| 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 brentuximab vedotin. Patients who have experienced a prior infusion-related reaction should be given premedication (e.g. paracetamol, an antihistamine and a corticosteroid) for subsequent infusions. Read more about Hypersensitivity reaction |
| Emetogenicity MODERATE | Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy. Even though a combination of an NK1 receptor antagonist, 5HT3, and a steroid is available on the on the PBS for the prevention of nausea and vomiting associated with all moderate to highly emetogenic anti-cancer therapies, we have opted not to include the NK1 in the treatment schedule. As a steroid has been included as part of this protocol, additional antiemetic steroids are not required. 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 POevery 6 hours when necessary. Read more about preventing anti-cancer therapyinduced 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:
Baseline clinical assessments includeechocardiogram (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 |
| Progressive multifocal leukoencephalopathy | Reactivation of the John Cunningham virus (JCV) in patients who have received brentuximab vedotin after receiving multiple chemotherapy regimens previously has resulted in progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal opportunistic viral infection of the brain. Patients must be monitored for any new or worsening neurological symptoms. Brentuximab vedotin treatment may have to be withheld if PML is suspected or discontinued if diagnosis is confirmed. Read more about progressive multifocal leukoencephalopathy and the Therapeutic Goods Administration Medicines Safety update on progressive multifocal leukoencephalopathyfrom the Australian Government, Department of Health. |
| Pancreatitis | Pancreatitis is uncommon but has been reported. Unexplained abdominal pain should be promptly investigated to include measurement of serum amylase and lipase. |
| Pulmonary toxicity | Brentuximab vedotin has been associated with pulmonary toxicity. Patients should be monitored for pulmonary symptoms (e.g. cough, dyspnoea). If new or worsening pulmonary symptoms occur, a prompt diagnostic evaluation should be performed and patients should be treated appropriately. Read more about pulmonary toxicity associated with anti-cancer drugs. |
| Peripheral neuropathy | Assess prior to each treatment. If a patient experiencesgrade 2 or greater peripheral neuropathy, a dose reduction,delay,or omission of treatment may be required; review by medical officer before commencing treatment. Read more about peripheral neuropathy Link to chemotherapy-induced peripheral neuropathy screening tool |
| Skin toxicity | Severe cutaneous adverse reactions (SCARs) havebeen observed in patients receiving brentuximab vedotin. This includes rare cases of drug reaction with eosinophilia and systemic symptoms (DRESS) and sometimes fatal cases of Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Monitor for rash, erythema and pruritus and discontinue treatment where clinically indicated. |
| 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 |
| Tumour lysis risk | Patients are at high risk of developing tumour lysis syndrome, prophylaxis is recommended. Read more about theprevention and management of tumour lysis syndrome. |
| PJP prophylaxis | PJP prophylaxis at the discretion of the treating clinician. Read more aboutprophylaxis of pneumocystis jiroveci (carinii) in cancer patients |
| Antiviral prophylaxis | Read more aboutantiviral prophylaxis drugs and doses |
| Antifungal prophylaxis | Read more about antifungal prophylaxis drugs and doses. |
| 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 thePBS website |
| Irradiated blood components | The use of irradiatedof blood components is recommended for patients receiving this treatment. Read more about the indications for the use of irradiated blood components |
| Blood tests | FBC, EUC, eGFR, LFTs, LDH and BSL baseline then 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 contraceptionwhilst 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 |
Dose modifications
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-cancerregimen (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 patientpreferences.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-haematologicalgradingsare based onCommon Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see.
Note: All dose reductions are calculated as a percentage of the starting dose.
| Haematological toxicity | |
| ANC x 109/L, Plateletsx 109/L(pre-treatment blood test) | |
| ANC less than 1.0 | Delay treatment until recovery and resume brentuximab vedotin at the same dose.Recommend addingG-CSFfor subsequent cycles (if not already added). |
| Platelets less than 75 | Dose modification is not generally indicated. Consider treatment delay |
Kidney dosing recommendations
- Suggested dose modifications are based on the International Consensus Guideline on Anticancer DrugDosing 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) | Cyclophosphamide | Doxorubicin | Brentuximab* | Prednisolone* |
|---|---|---|---|---|
| ≥ 60 | Full dose | Full dose | There is no clinical trial experience using brentuximab in combination with chemotherapy in patients with kidney dysfunction, where serum creatinine is ≥ 0.177 mmol/L or eGFR ≤ 40 mL/minute. Use of brentuximab in combination with chemotherapy should be avoided in patients with severe kidney dysfunction | No dose reduction required in kidney dysfunction. |
45 - 59 | Full dose | Full dose | ||
| 30 - 44 | Full dose | Full dose | ||
| 15 - 29 | Full dose Potential for increased risk of adverse events | Full dose | ||
| < 15 (without kidney replacement therapy) | Consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing. | Full dose | ||
* This drug was not included in the ADDIKD guideline. | ||||
| Hepatic impairment | ||
|---|---|---|
| Hepatic dysfunction | ||
| Use with caution in patients with hepatic impairment, due to potential increased exposure to MMAE (conjugated anti-microtubule agent) and increased toxicity. | ||
| Bilirubin > 1.5 x ULN (unless due to Gilbert syndrome) or AST or ALT > 3 x ULN | No data available for brentuximab vedotin in combination with chemotherapy | |
| Moderate (Child-Pugh B) to Severe (Child-Pugh C) | Avoid brentuximabvedotinin combination with chemotherapy; consider alternate protocol | |
| Bilirubin (micromol/L) | |
|---|---|
| 20 to 50 | Reduce doxorubicin by 50% |
| 51 to 85 | Reduce doxorubicin by 75% |
| greater than 85 | Omit doxorubicin |
| Peripheral neuropathy(motor neuropathy,sensory neuropathy) | |
|---|---|
| Grade 2 motor neuropathy or grade 3 sensory neuropathy | Delay treatment until toxicity has resolved to grade 1 or baseline and reduce the dose of brentuximab vedotin to 1.2 mg/kg every 3 weeks(max. dose 120 mg)for subsequent cycles. |
| Grade 3 or greater motor neuropathy or grade 4 sensory neuropathy | Omit brentuximab vedotin |
| Dermatological reactions | |
|---|---|
| Severe cutaneous adverse reactions (SCARs) e.g.Steven-Johnson syndrome(SJS),toxic epidermal necrolysis(TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) | Discontinue brentuximab vedotin |
Interactions
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:
- MIMS - interactions tab (includes link to a CYP-450 table)(login required)
- Australian Medicines Handbook (AMH)– interactions tab(login required)
- Micromedex Drug Interactions (login required)
- Cancer Drug Interactions
- Cytochrome P450 Drug Interactions
For more information see.
| Brentuximabvedotin | ||
|---|---|---|
| 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 MMAE (conjugated anti-microtubule agent) possible due to reduced clearance | Avoid combination or monitor for MMAE toxicity and reduce the dose appropriately |
| CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John's wort etc.) | Reduced efficacy of MMAE possible due to increased clearance | Avoid combination or monitor for decreased clinical response to MMAE |
| Bleomycin | May have additive effect with brentuximab vedotin and is associated with pulmonary toxicity | Avoid combination as it is contraindicated |
| 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 |
| Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs) | Additive nephrotoxicity | Avoid combination or monitor kidney function closely |
| 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 etc.) | 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 |
| Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs etc.) | Additive nephrotoxicity | Avoid combination or monitor kidney function closely |
| 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, ritonavir etc.) | 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 |
| 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 |
| 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 CYP3A4andP‑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 |
Administration
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
- Day 2-5
- Discharge information
Day 1
Approximate treatment time: 2 hours
Safe handling and waste management
Safe administration
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 TIVADor CVAD.
- baseline weight
- dipstick urinalysis prior to treatment
Hydration ifprescribed
Treatment -Time out
Prednisolone
- administer orally ONCE a dayon 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.
Pre treatment medication
Verify antiemetics taken or administer as prescribed.
Chemotherapy -Time out
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 andexclude 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.
Cyclophosphamide
Administer cyclophosphamide:
- via IV infusionover 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.
Brentuximab vedotin
Administer brentuximabvedotin(irritant):
- via IV infusion over30 minutes
- flush with ~100 mL of sodium chloride 0.9%
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 with close monitoring.
- for severe reactions seek medical assistance immediately and do not restart infusion.
- premedication with paracetamol, an antihistamine and a corticosteroid should be considered for further doses for patients who have experienced a prior infusion related reaction.
Remove IV cannula and/or deaccessTIVAD or CVAD.
Continue safe handling precautions until 7 days after completion of drug(s)
- Day 1
- Day 2-5
- Discharge information
Day 2-5
This is an oral treatment
Prednisolone
- administer orally ONCE a dayon 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.
- Day 1
- Day 2-5
- Discharge information
Discharge information
Prednisolone tablets
- Prednisolone tabletswith written instructions on how to take them.
Antiemetics
- Antiemetics as prescribed.
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.
Side effects
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 |
|---|---|
| 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. |
| Flu-like symptoms | |
| Nausea and vomiting | Read more about prevention of treatmentinduced nausea and vomiting |
| 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 aboutimmediate management of neutropenic fever |
|---|---|
| Thrombocytopenia | A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding. Read more about thrombocytopenia |
| Abdominal pain | Dull ache, cramping or sharp pains are common with some anti-cancer drugs. These are caused by either increased or decreased gastrointestinal motility and can be associated with diarrhoea or constipation. |
| Anorexia | Loss of appetite accompanied by decreased food intake. Read more about anorexia |
| Arthralgia and myalgia | Generalised joint pain or and/or stiffness and muscle aches, often worse upon waking or after long periods of inactivity. Can improve with movement. May be mild or severe, intermittent or constant and accompanied by inflammation. Read more about arthralgia and myalgia |
| Constipation | |
| Diarrhoea | Read more about treatment induced diarrhoea |
| Dizziness | Feeling faint or lightheaded, weak or unsteady. Advise patients to stand up slowly from sitting down or lying down positions and increasefluid intake if dehydrated. |
| Dyspnoea | |
| Fatigue | Read more about fatigue |
| Fever | |
| Headache | |
| Haemorrhagic cystitis | An inflammatory process, characterised by diffuse bladder mucosal inflammation resulting in haemorrhage. Patients are at risk following blood and marrow transplant (BMT) or treatment with cyclophosphamide, ifosfamide and/or radiation therapy. Read more about haemorrhagic cystitis |
| Hepatotoxicity | Anti-cancer drugsadministered either alone or in combination with other drugs and/or radiationmay cause direct or indirect hepatotoxicity. Hepatic dysfunction can alter the metabolism of some drugs resulting in systemic toxicity. |
| Hyperglycaemia | High blood sugar, an excess of glucose in the blood stream. |
| Oral mucositis | 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 |
| Pancreatitis | Inflammation of the pancreas with impairment of function is associated with treatment. |
| 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 |
| Respiratory tract infection | |
| 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) and drug reaction with eosinophilia and systemic symptoms (DRESS). Onset may occur anytime between 1to 6 weeks after drug exposure and the course of the illness can last from weeks to months. If SCARs occur, discontinue treatment immediatelyand seek specialist opinion to determinedifferential diagnosisso that appropriate supportive treatment can be administered. |
| 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) | |
| Anaemia | Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. Read more about anaemia |
|---|---|
| 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 alopeciaand scalp cooling |
| Progressive multifocal leukoencephalopathy (PML) | A rare opportunistic viral infection of the brain, usually leading to death or severe disability, can occur with monoclonal antibodies (e.g. rituximab, obinutuzumab, ofatumumab, brentuximab vedotin) and other targeted therapies (e.g. ibrutinib,ruxolitinib, idelalisib). Onset may occur up to months after the final dose. Read more about progressive multifocal leukoencephalopathy (PML) |
| 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 |
| 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 |
|---|---|
Evidence
The ECHELON-2 trialr was a double-blind phase 3 study from 17 countries of untreated peripheral T-cell lymphoma (PTCL) in patients whose lymphoma had at least 10% of cells expressing CD30. Histological subtypes included anaplastic large cell lymphoma(ALCL)ALK-negative, ALCL ALK-positive with an International Prognostic Index (IPI) score of 2 or higher, PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), adult T-cell leukaemia/lymphoma, enteropathy associated lymphoma, and hepatosplenic T-cell lymphoma. There was a 1:1 randomisation to brentuximab vedotin, cyclophosphamide,doxorubicinand prednisolone (BV-CHP) or cyclophosphamide,doxorubicin, vincristine and prednisolone (CHOP) for 6-8 cycles. A consolidative stem cell transplant (SCT)or radiotherapy could be performed at the end of the chemotherapy at the investigator’s discretion.
452 patients were randomised. 70% had systemicanaplastic large cell lymphoma(sALCL) and the median age was 58 years. The primary endpoint was progression-free survival (PFS).r
Real world data reinforced the superiority of BV-CHP vs. CHOP with a retrospective analysis of 1344 patients with PTCL treated with BV-CHP (n=749) vs. CHOP (n=595).rThe most common subtypes were sALCL , PTCL-NOS and AITL. After propensity matching, patients treated with CHOP had a higher likelihood of receiving a second-line therapy during the follow-up period(HR 1.64).r
Efficacy
The median PFS was 62.3 months for BV-CHP and 23.8 months for CHOP (figure 1) giving a 30% reduction in progression events.rCompared with CHOP, BV-CHP significantly reduced the risk of death by 34% (figure 2).After a median follow-up of 47.6 months, the median overall survival (OS) was not reached for either group. The estimated 5-year OS was 70.1% the BV-CHP arm versus 61.0% for the CHOP arm. 5 year follow up data showed that all patients subgroups benefited of the treatment including those with high IPI scores.
Rates of consolidative SCT were higher in the BV-CHP arm than in the CHOP arm(22% vs. 17%) whilst consolidative systemic anticancer therapy was higher in the CHOP cohort; (31% vs. 45%).r Amongthe 114 patients who achieved CR following BV-CHP, those who underwent a subsequent SCT had a 64% reduction in the risk of a PFS event with the estimated 3-year PFS of 80.4% in patients who underwent SCT compared to 54.9% in those who didn’t, although this analysis was limited by case numbers.r
The study was not powered to compare the efficacy between the histological subtypes but prespecified subgroup analysis was consistent with the overall study result. In the sALCL subgroup the 5-year PFS was 60.6% for BV-CHP and 48.4% for CHOP.r
Figure 1.Progression-free survivalr
©Ann Oncol2022
Figure 2.Overall survival for the intention-to-treatpopulationr
©Ann Oncol2022
Toxicity
Adverse events were similar in each arm.
Table 1. Adverse eventsr
© Lancet 2019
References References
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Literature search
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History
Version 3
| Date | Summary of changes |
|---|---|
| 20/03/2024 | 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.3. |
Version 2
| Date | Summary of changes |
|---|---|
| 19/12/2023 | Reviewed out of session by Haematology Reference Committee. Updates include:
Increase to v.2. Review in 2years. |
Version 1
| Date | Summary of changes |
|---|---|
| 22/10/2021 | New protocol presented at the Haematology Reference Committee Meeting. Discussion continued offline, approved for publication. |
| 31/08/2022 | Brentuximab vedotin extravasation category updated to align with extravasation clinical resources update. |
| 11/11/2022 | Protocol reviewed electronically by the Haematology Reference Committee, nil changes. Review in 2 years |
