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.
IFOS
Sarcoma - Soft Tissue
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.
Sarcomas are rare tumours and as such benefit from referral to specialized centres where there will be access to multidisciplinary expertise including good radiology, orthopedic and thoracic surgery, medical oncology, radiation oncology, pathology, and other supportive care disciplines.
Multiple regimens exist with various dosing schedules, an option would be:
|
ifosfamide
| 1500 mg/m2 to 3000 mg /m² | IV | Days 1 to 3 |
| mesna | |||
|
Evidence-based mesna dosing can be variable, an option would be:
|
|||
REPEAT EVERY 21 DAYS
For a usual total of 6 cycles unless disease progression or unacceptable toxicity occurs
Moderate
Other Supportive Care:
- Use standard alkalinization / hydration regimens for ifosfamide.
- Inadequate total hydration may result in dose-related hemorrhagic cystitis.
Also refer to CCO Antiemetic Summary
Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are in use at some centres.
Dosage with toxicity
Dosage in myelosuppression:
Modify according to protocol by which patient is being treated; if no guidelines available, refer to Appendix 6 "Dosage Modification for Hematologic and Non-Hematologic Toxicities."
|
Worst Toxicity / Counts (x 109/L) in previous cycle |
|
Worst Toxicity / Counts (x 109/L) in previous cycle |
Ifosfamide (% previous dose)* |
| Febrile Neutropenia Or ANC < 0.5 for ≥ 5-7 days |
Or
|
Thrombocytopenic bleeding Or Platelets < 25 |
↓ 20% or consider GCSF for isolated neutropenia |
|
ANC ≥ 1.5 |
Or
|
Platelets ≥ 100 |
100%
|
|
Somnolence or other signs of encephalopathy |
|
|
Hold; methylene blue 50mg IV q4h until resolution. Consider prophylactic methylene blue for subsequent cycles. Consider discontinuing or dose reduction for next cycle. |
|
Grade 3 or 4 neurotoxicity |
|
|
Discontinue
|
|
Grade 3 related organ / non-hematologic |
|
|
↓ 20%
|
|
Grade 4 related organ / non-hematologic LVEF ≤ 45% |
|
|
Discontinue
|
|
* Do not retreat until ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and toxicity recovered to ≤ grade 2. |
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Management of Urotoxicity
|
Finding
|
Action
|
|
Microscopic hematuria |
Hold ifosfamide until resolves
|
|
Macroscopic hematuria |
Discontinue or reduce dose
|
Hepatic Impairment
|
Bilirubin
|
|
AST/ALT
|
Ifosfamide* |
|
1-2 x ULN |
and/ or
|
<2 x ULN
|
100%
|
|
2-4 x ULN |
2-5 x ULN
|
75%
|
|
|
> 4 x ULN |
> 5 x ULN
|
Discontinue
|
Renal Impairment
|
Ifosfamide
(% previous dose) |
|
|
> 60 |
100% |
|
40-60 |
75% |
|
20-40 |
50% |
|
< 20 |
Discontinue |
Refer to ifosfamide, mesna drug monograph(s) for additional details of adverse effects
| Most Common Side Effects |
Less Common Side Effects, but may be |
|
|
Refer to mesna, ifosfamide drug monograph(s) for additional details
Recommended Clinical Monitoring
- CBC; baseline and at each visit
- Urinalysis, for RBCs; before each dose
- Liver function tests; baseline and regular
- Renal function tests and electrolytes; baseline and regular
- Clinical assessment of neurotoxicity (especially in patients with increased risk) infection, bleeding, local toxicity and cystitis; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Ifosfamide and mesna drug monographs, Cancer Care Ontario.
Soft Tissue:
Bramwell VH, Mouridsen HT, Santoro A, et al. Cyclophosphamide versus ifosfamide: final report of a randomized phase II trial in adult soft tissue sarcomas. Eur J Cancer Clin Oncol 1987;23(3):311-21.
Lorigan P, Verweij J, Papai Z, et al. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer soft tissue and bone sarcoma group study. J Clin Oncol 2007;25:3144-50.
Osteogenic:
Daw NC, Billups CA, Rodriguez-Galindo C, et al. Metastatic osteosarcoma. Cancer 2006;106(2):403-12.
Harris MB, Gieser P, Goorin AM, et al. Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study. J Clin Oncol 1998;16(11):3641-8.
Magrath I, Sandlund J, Raynor A, et al. A phase II study of ifosfamide in the treatment of recurrent sarcomas in young people. Cancer Chemother Pharmacol 1986;18 Suppl 2:S25-8.
Marti C, Kroner T, Remagen W, et al. High-dose ifosfamide in advanced osteosarcoma. Cancer Treat Rep 1985;69(1):115-7.
November 2017 aligned disease site with CCO website, aligned mesna dosing with QBP
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
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