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.
TIP
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 relapsed testicular germ cell tumours. This was studied in a phase II trial involving patients who failed to achieve a continuous CR to a prior platinum-based regimen, and have other prognostic features for achieving a favourable outcome to conventional-dose cisplatin-based salvage chemotherapy.
Adapted for outpatient administration:
| PACLitaxel | 250 mg /m² | IV over 3 hours | Day 1 |
| mesna | 500 mg /m² | IV immediately before ifosfamide | Days 2 to 5 |
| ifosfamide | 1500 mg /m² | IV | Days 2 to 5 |
| CISplatin | 25 mg /m² | IV | Days 2 to 5 |
| mesna | 500* mg /m² | IV at 4 and 8 hours post-ifosfamide | Days 2 to 5 |
|
(*or mesna 1000 mg/m2 PO) |
|||
REPEAT EVERY 21 DAYS
For a maximum of 4 cycles, unless disease progression or unacceptable toxicity occurs
Low (D1)
Moderate (D2-5)
High
Other Supportive Care:
Paclitaxel: Patients should be pretreated with a corticosteroid as well as an antihistamine and a H2 blocker: For example:
- DEXAMETHASONE 20mg PO 12 & 6 hours or 20mg IV 30 minutes before paclitaxel
- DIPHENHYDRAMINE 50mg IV 30 minutes before paclitaxel
- RANITIDINE 50mg IV 30 minutes before paclitaxel
Standard regimens for Cisplatin premedication and hydration should be followed. Refer to local guidelines.
Ifosfamide: Oral/IV hydration is strongly encouraged. Poorly hydrated patients may need more IV hydration. Inadequate total hydration may result in dose-related hemorrhagic cystitis.
Filgrastim 5 mcg /kg SC on days 7 to 18 (until ANC > 1 x 109/L) has been used in clinical trials.
Also refer to CCO Antiemetic Recommendations.
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
There were no dose reductions in the clinical trial. Recovery from toxicities were required before re-treatment with a subsequent cycle.
|
Worst Toxicity / Counts (x 109/L) in previous cycle |
PACLitaxel
(% previous dose)
|
ifosfamide
(% previous dose)
|
cisplatin
(% previous dose)
|
|
Somnolence or other signs of encephalopathy |
100%
|
Hold; methylene blue 50mg IV q4h until resolution. Consider prophylactic methylene blue for subsequent cycles, or consider discontinuing for next cycle |
100%
|
|
Hematuria
|
100%
|
Hold until resolution if microscopic; if macroscopic reduce dose or discontinue |
100%
|
|
Grade 3 neurotoxicity
|
Discontinue
|
||
|
Grade 4 related organ / non-hematologic |
Discontinue
|
||
*In the clinical trial, re-treatment with a subsequent cycle required a neutrophil count of ≥ 0.45 x 109/L and a platelet count of ≥ 75 x 109/L.
Paclitaxel - Dosage after Hypersensitivity:
- For mild symptoms (e.g., mild flushing, rash, pruritus) attempt to complete the infusion under close supervision.
- For moderate symptoms (e.g., moderate rash, flushing, mild dyspnea, chest discomfort, mild hypotension),
- Stop the paclitaxel infusion and give diphenhydramine 25-50 mg IV and methylprednisolone 125 mg IV.
- Once symptoms have resolved, resume paclitaxel infusion at a rate of 10% of original rate for 15 minutes, then at 25% of original rate for 15 minutes, and if no further symptoms develop, continue at original rate until infusion is complete.
- For severe symptoms (e.g., one or more of: respiratory distress requiring treatment, generalized urticaria, angioedema, hypotension requiring therapy),
- Stop the paclitaxel infusion; give diphenhydramine and methylprednisolone as above. Use epinephrine or bronchodilators if indicated.
- Do not rechallenge with paclitaxel.
Filgrastim: Hold ± discontinue for ARDS or alveolar hemorrhage.
Hepatic Impairment
|
Bilirubin |
AST/ALT |
PACLitaxel |
ifosfamide (% previous dose) |
cisplatin (% previous dose) |
|
|
1-2 x ULN |
and/or | < 2 x ULN |
|
100% |
No change |
|
>2-4 x ULN |
and/or | 2-5 x ULN |
↓ to 135mg/m2 |
75% |
No change |
|
>4 x ULN |
and/or | > 5 x ULN |
↓ to 50mg/m2 or omit |
Discontinue |
No change |
Renal Impairment
|
Creatinine Clearance (mL/min) |
PACLitaxel (% previous dose) |
ifosfamide (% previous dose) |
cisplatin (% previous dose) |
|
>60 |
No change |
100% |
100% |
|
>45-60 |
No change |
75% |
75% |
|
>30-45 |
No change |
50% |
50% |
| 20-30 | No change | 50% | Discontinue |
|
<20 |
No change |
Discontinue |
Discontinue |
Refer to PACLitaxel, mesna, ifosfamide, CISplatin, filgrastim drug monograph(s) for additional details of adverse effects
| Most Common Side Effects |
Less Common Side Effects, but may be |
|
|
Refer to PACLitaxel, mesna, ifosfamide, CISplatin, filgrastim drug monograph(s) for additional details
Recommended Clinical Monitoring
- CBC; baseline and regular
- Liver function tests; baseline and regular
- Renal function tests, baseline and regular
- Urinalysis, for RBCs; before each ifosfamide dose and regular
- Electrolytes, including magnesium, phosphate and calcium; baseline and regular
- Blood pressure and pulse rate monitoring during infusion, cardiac monitoring with prior arrhythmia;
- Clinical toxicity assessment (infection, bleeding, musculoskeletal pain, thromboembolism, cutaneous effects, hypersensitivity, cystitis, nausea/vomiting, neurotoxicity, ototoxicity); at each visit
- Audiogram; as clinically indicated
- Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- CBC; 2-3 times a week during filgrastim therapy
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Feldman DR, Hu J, Dorff TB, et al. Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors. J Clin Oncol 2016;34(21):2478-83.
Kondagunta GV, Bacik J, Donadio A, et al. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol 2005;;23(27):6549-55.
Mead GM, Cullen MH, Huddart R, et al. A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial. Br J Cancer 2005;93(2):178-84.
Motzer RJ, Sheinfeld J, Mazumdar M, et al. Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer. J Clin Oncol 2000 Jun;18(12):2413-8.
March 2021 modified dosing section
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.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, 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.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.