Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
CISPDOXOETOPMTTN
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
Treatment of patients with metastatic or locally advanced unresectable adrenocortical carcinoma, who have good performance status, no prior radiation or chemotherapy treatment (except adjuvant mitotane) and have no brain metastases. A phase III clinical trial has shown significantly higher response rate and progression-free survival, but similar overall survival and toxicity compared to streptozocin-mitotane.
mitotane
ODB - General Benefit
(mitotane)
(ODB Formulary
)
| DOXOrubicin | 40 mg /m² | IV | Day 1 |
| etoposide | 100 mg /m² | IV | Days 2, 3, and 4 |
| CISplatin | 40 mg /m² | IV | Days 3 and 4 |
| mitotane | 1 to 4 g | PO | Daily as tolerated, start 1 week before chemotherapy * |
|
*(Outpatient prescription in multiples of 500 mg tablets; to reach mitotane blood level of 14-20 mg/L) |
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REPEAT EVERY 28 DAYS
• Cisplatin-Doxorubicin-Etoposide: For a usual maximum of 6 cycles, or until disease progression in the absence of unacceptable toxicity
• Mitotane: Until disease progression or unacceptable toxicity occurs
Moderate (Mitotane: Adjust according to symptoms)
Other Supportive Care:
- Supplement with replacement cortisone (glucocorticoid) and fludrocortisone (mineralocorticoid) (See mitotane drug monograph.)
- Standard regimens for Cisplatin premedication and hydration should be followed. Refer to Cisplatin monograph.
Also refer to CCO Antiemetic Summary
Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from clinical trials or product monographs and could be considered.
Dosage with toxicity
|
Worst Toxicity / Counts (x 109/L) in previous cycle |
|
Worst Toxicity / Counts (x 109/L) in previous cycle |
DOXOrubicin
(% previous dose)
|
CISplatin
(% previous dose)
|
etoposide
(% previous dose)
|
Mitotane
(% previous dose)
|
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|
Febrile Neutropenia
Or
ANC < 0.5 for ≥ 5-7 d
|
Or
|
Thrombocytopenic bleeding
Or
Platelets < 25
|
Hold *, then 75%
|
No change
|
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|
Cardiotoxicity**
|
|
|
Discontinue
|
No change |
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|
Grade 2 neurotoxicity /ototoxicity |
|
|
No change |
75%
|
No change |
Caution
|
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|
Grade 3 or 4 neurotoxicity/ototoxicity |
|
|
No change
|
Discontinue
|
No change |
Hold* or discontinue |
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|
Grade 3 related organ / non-hematologic
|
|
|
*75% for suspect drug(s)
|
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|
Grade 4 related organ / non-hematologic
Hemolysis, optic neuritis, arterial thromboembolism, severe hypersensitivity reactions |
|
|
Discontinue
|
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*Do not start new cycle until toxicities have recovered to ≤ grade 2, platelets ≥ 100 x 109/L, creatinine ≤ grade 1 and ANC ≥ 1.5 x 109/L.
**including any signs and symptoms of heart failure, greater than 10% decline in LVEF to below the lower limit of normal, a greater than 20% decline in LVEF from any level, or LVEF ≤ 45%.
Hepatic Impairment
|
Bilirubin
|
Cisplatin
|
Doxorubicin (% previous dose)
|
Etoposide (% previous dose)
|
Mitotane^ (% previous dose)
|
|
1-2 x ULN
|
No change
|
50%
|
50%
|
50%
|
|
>2 – 4 x ULN
|
25%*
|
25%
|
25%
|
|
|
> 4 x ULN
|
Discontinue*
|
Discontinue
|
Discontinue
|
|
|
* Consider 75% dose reduction or OMIT dose for severe increases in LFTs (i.e. > 5 x ULN)
^ suggested – no specific recommendations found
|
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Renal Impairment
|
Creatinine clearance |
Doxorubicin |
Cisplatin (% previous dose) |
Etoposide (% previous dose) |
Mitotane*
|
|
>45-60
|
No adjustment required |
75%
|
100%
|
75-100%
|
|
>30-45
|
50%
|
75%
|
75%
|
|
|
15-30
|
Discontinue
|
75%
|
75%
|
|
|
<15
|
Discontinue
|
Discontinue
|
50% or discontinue |
Refer to DOXOrubicin, CISplatin, etoposide, mitotane drug monograph(s) for additional details of adverse effects
|
Most common side effects |
Less common but may be severe or life-threatening |
· |
|
Refer to DOXOrubicin, CISplatin, etoposide, mitotane drug monograph(s) for additional details
Refer to DOXOrubicin, CISplatin, etoposide, mitotane drug monograph(s) for additional details
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Recommended Clinical Monitoring
- CBC; baseline and regular
- Liver function tests; baseline and regular
- Renal function tests; baseline and regular
- Electrolytes, including magnesium, phosphate and calcium; baseline and regular
- Cardiac tests for all patients with cardiac risk factors (including prior trastuzumab or patients at or above the threshold dose levels (doxorubicin 400mg/m2 for q21 day schedules and 550mg/m2 for weekly schedules); baseline and periodic
- Clinical toxicity assessment (infection, bleeding, mucositis, adrenal insufficiency, cardiotoxicity, thromboembolism, GI, nausea/vomiting, local toxicity, infusion reactions, neurotoxicity, ototoxicity); at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Fassnacht M, Terzolo M, Allolio B, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med 2012;366(23):2189-97.
November 2021 Added mitotane public funding info
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
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