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CISPVINO(RT)
Curative
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.
Chemo-radiotherapy for patients with unresected, clinical or pathological stage III NSCLC with good performance status (ECOG ≤ 1) and minimal weight loss (<5% in the past 3 months).
Chemoradiotherapy - Chemotherapy concurrent with Radiotherapy
vinorelbine 1 | 15 mg /m² | IV | Days 1 and 8 |
1 Note: Dosage of vinorelbine reduced with concurrent radiation as full doses are intolerable. |
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CISplatin | 80 mg /m² | IV | Day 1 |
REPEAT EVERY 21 DAYS DURING RADIOTHERAPY
Notes: There is limited evidence for induction chemotherapy prior to chemo-radiation and it is not recommended. There is also limited evidence for ‘consolidation’ chemotherapy after the completion of chemo-radiation; if used, 2 to 3 cycles could be considered.
High (Cisplatin )
Minimal (Vinorelbine Only days)
Moderate
Other Supportive Care:
Also refer to CCO Antiemetic Summary
Standard regimens for Cisplatin premedication and hydration should be followed. Refer to Cisplatin monograph
Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are based on Vokes (2002) and the Drug Monographs for each drug.
Dosage with toxicity
Hematologic Toxicities:
Granulocyte counts (x 109/L) on treatment day |
Platelet Counts (x 109/L) on treatment day |
Dose1 |
1 to 1.4 | 50 to 75 | Cisplatin and Vinorelbine ↓ by 50% |
<1 | <50 | Hold Cisplatin and Vinorelbine doses |
1 Vokes et al
Non-hematologic toxicities
Worst Toxicity / Counts (x 109/L) Experienced |
Cisplatin (% previous dose)* |
Vinorelbine (% previous dose)* |
Grade 2 neurotoxicity |
↓ to 50%1 |
↓ to 50%1 |
Grade 3 neurotoxicity |
Discontinue |
Discontinue |
Grade 3 or 4 radiotherapy related toxicities |
No change1 |
Hold, then ↓ 50%1 |
↑ creatinine (1.5 to 1.99 x ULN) |
↓ by 50% |
No change |
↑ creatinine (≥ 2x ULN) |
Hold until recovered to ≤ 2 x ULN and ↓ as indicated |
No change |
Other related grade 3 non-hematologic/organ |
Hold; reduce by 25% |
Hold; reduce by 25% |
Other related grade 4 non-hematologic/organ |
Consider discontinuing |
Consider discontinuing |
*Do not re-treat until toxicities have recovered to ≤ grade 2
1 Vokes 2002
Hepatic Impairment
Suggested adjustments for increases in total bilirubin:
Total Bilirubin (µmol/L) |
Cisplatin (% usual dose) |
Vinorelbine (% usual dose) |
< 2 x ULN |
No adjustment needed |
100% |
2 to 3 x ULN |
50% |
|
> 3 x ULN |
25% |
Renal Impairment
See specific protocol. In general, renal function should have normalized before patients are re-treated. If continued treatment is considered to be mandatory, the following dose modifications could be considered at the physician's discretion (Kintzel 1995).
Creatinine clearance |
Cisplatin (% usual dose) |
Vinorelbine (% usual dose) |
46 to 60 |
75% |
No adjustment needed |
30 to 45 |
50% |
|
<30 |
Discontinue |
Dosage in the Elderly:
Geriatric patients may be at higher risk of developing nephrotoxicity, ototoxicity/neurotoxicity or hematologic adverse effects with cisplatin
Refer to vinorelbine, CISplatin drug monograph(s) for additional details of adverse effects
Most Common Side Effects |
Less Common Side Effects, but may be |
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Refer to vinorelbine, CISplatin drug monograph(s) for additional details
- Avoid nephrotoxic and ototoxic drugs (i.e. aminogycosides) due to additive effects
- Concomitant use of renally excreted drugs (i.e. methotrexate) may decrease renal clearance and enhance toxicities of these drugs. Avoid use, if possible. If not possible, modify doses as necessary.
- Avoid strong CYP3A4 inhibitors (i.e. ketoconazole)
Refer to vinorelbine, CISplatin drug monograph(s) for additional details
Drug Administration:
Cisplatin:
- Follow local hydration protocols to prevent/minimize nephrotoxicity
- Dilute in NS and administer IV over 30-60 minutes
- Blood pressure should be taken before and after chemotherapy.
- Oral hydration with 8 glasses of fluid per day is strongly encouraged on treatment day and for 1-2 days after cisplatin; if nausea and vomiting prevent oral hydration, the patient may need to return for more IV hydration.
- Cisplatin is physically incompatible with any IV set, needle or syringe containing aluminum.
- Store unopened vials between 15°C to 25°C and protect from light. Do not refrigerate or freeze since precipitation will occur.
Vinorelbine:
FOR INTRAVENOUS USE ONLY.
Intrathecal administration of other vinca alkaloids has resulted in death. Syringes containing this product should be labeled “WARNING – FOR INTRAVENOUS USE ONLY. FATAL if given intrathecally.”
- Dilute in a 50mL minibag (D5W, NS) to a final concentration 0.5 - 2mg/mL; infuse over 6-10 minutes through free-flowing IV.
- Or may push (at final concentration of 1.5 – 3mg/mL) through sidearm of free-flowing IV (D5W, NS); inject over 6-10 minutes.
- Flushing the line before and after administration of vinorelbine may reduce injection site reactions and phlebitis risk.
- Refrigerate unopened vials (2-8°C); protect from light and do not freeze.
Contraindications:
- Known hypersensitivity to platinum containing compounds or vinca alkaloids
- Patients who have severe myelosuppression
- Pre-existing renal impairment and hearing impairment, unless the possible benefits of treatment outweigh the risks.
Other Warnings/Precautions:
- Patients with pre-existing neuropathy or prior treatment with other neurotoxic drugs may have increased potential for neurotoxicity
Recommended Clinical Monitoring
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
- CBC; Baseline and before each dose
- Liver function tests; Baseline and before each dose
- Renal function tests; Baseline and before each cisplatin dose
- Electrolytes, including magnesium, sodium, potassium, phosphate and calcium.; Baseline and before each cisplatin dose
- Audiogram; Baseline and as clinically indicated
- Clinical toxicity assessment for signs of neurotoxicity, local toxicity, bleeding, infection, nausea/vomiting, neurotoxicity, ototoxicity, hypersensitivity, thromboembolism, lung toxicity; at each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Cisplatin and vinorelbine drug monographs, Cancer Care Ontario.
Fournel P, Robinet G, Thomas P, et al. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95-01 Study. J Clin Oncol 23:5910-5917.
June 2019 Added PEBC guideline link
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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