Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
CRBPPACL
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 locally advanced or metastatic lung cancer
| PACLitaxel | 175-200 mg /m² | IV over 3 hours | Day 1 |
| CARBOplatin | AUC 5 to 6* | IV | Day 1 |
|
*Adjust Carboplatin dose to AUC target (using Calvert formula) as outlined in "Other Notes" section. |
|||
REPEAT EVERY 21 DAYS
For 4 to 6 cycles in responding patients unless disease progression or unacceptable toxicity occurs
Moderate + NK1 antagonist (Carboplatin AUC ≥ 5)
Also refer to CCO Antiemetic Recommendations.
Pre-medications (prophylaxis for infusion reaction):
Paclitaxel*:
- Dexamethasone 20 mg PO 12- and 6-hours OR Dexamethasone 20 mg IV 30 minutes pre-infusion†
- Diphenhydramine 25-50 mg IV/PO 30-60 minutes pre-infusion
- Ranitidine 50 mg IV OR Famotidine 20 mg IV 30-60 minutes pre-infusion
*Consider discontinuing pre-medications for paclitaxel if there was no IR in the first 2 doses.
†Oral and IV dexamethasone are both effective at reducing overall IR rates. Some evidence suggests that oral dexamethasone may be more effective for reducing severe reactions; however, adverse effects and compliance remain a concern.
Carboplatin:
-
There is insufficient evidence that routine prophylaxis with pre-medications reduce infusion reaction (IR) rates.
-
Corticosteroids and H1-receptor antagonists ± H2-receptor antagonists may reduce IR rates for some patients (e.g. gynecological patients with a platinum-free interval (PFI) > 12 months or a history of drug allergy who are receiving carboplatin starting from the 7th cycle) but no optimal pre-medication regimen has been established.
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
Suggested Dose Levels for Paclitaxel:
|
Dose Level |
Paclitaxel (mg/m2) |
Paclitaxel (mg/m2) |
|
0 |
200 |
175 |
|
-1 |
175 |
135 |
|
-2 |
150 |
110 |
|
Worst Toxicity (Counts x 109/L) |
Carboplatin |
Paclitaxel |
|
ANC < 1.5 for > 7 days |
Hold1; No change upon restart |
Hold1, then |
| ANC < 0.5 for ≥ 7 days or Febrile Neutropenia |
Hold1; ↓ 1 AUC upon restart |
Hold1, then |
| Platelets < 25 or Thrombocytopenic bleeding |
Hold1; ↓ 1 AUC upon restart |
Hold1; ↓ 1 dose level upon restart2 |
| Grade 2 neuropathy | No change | Omit or consider ↓ 1 dose level |
|
Grade 3 neuropathy |
No change |
Omit or ↓ 1 dose level2 |
| Other Grade 3 non-hematologic toxicity |
Hold1; ↓ 1 AUC upon restart |
Hold1; ↓ 1 dose level upon restart |
|
Grade 4 non-hematologic toxicity |
Discontinue |
Discontinue |
| Any grade cystoid macular edema | No change | Discontinue |
1Do not start new cycle until ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, and non-hematological toxicities have recovered to ≤ grade 2.
2In some clinical studies, paclitaxel dose started at 200mg/m2; If starting at this dose, reduce by 2 dose levels for grade 4 hematologic toxicity, including febrile neutropenia or thrombocytopenic bleeding, or grade 3 neuropathy.
Management of Infusion-related Reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge | |
| Carboplatin / Paclitaxel | Carboplatin# | Paclitaxel | |
| 1 or 2 |
Restart:
|
|
|
| 3 or 4 |
|
|
|
#There is evidence that re-challenging with cisplatin after carboplatin reaction can be a viable option, however, exact cross reactivity between platinum agents is not known, but can be as high as 25%.
*Up to 50% of patients can experience recurrent reactions during re-challenge despite using pre-medications (e.g. corticosteroid and H1/H2-receptor antagonist).
Hepatic Impairment
For paclitaxel, caution and dose reduction are advised in patients with moderate to severe hepatic impairment. Patients receiving paclitaxel with hepatic impairment may be at risk of toxicity, especially severe myelosuppression.
Suggested dose modifications are:
|
Bilirubin |
|
AST/ALT |
PACLitaxel (% usual dose) |
CARBOplatin (% usual dose) |
|
≤ 1.25 x ULN |
AND |
2 to 10 x ULN |
75% |
No change
|
|
1.26 to 2.5 x ULN |
AND |
< 10 x ULN |
40% |
|
|
2.6 to 4 x ULN |
AND |
< 10 x ULN |
25% |
|
|
> 4 x ULN |
AND/OR |
≥ 10 x ULN |
Consider risk-benefit or Omit |
Renal Impairment
|
Creatinine Clearance (mL/min) |
Paclitaxel |
Carboplatin |
|
20 - 50 |
No change |
Use Calvert formula* |
|
< 20 |
Discontinue |
*Refer to "Other Notes" section.
Dosage in the Elderly
No adjustment required, but elderly patients are more at risk for severe toxicity. Caution should be exercised and dose reduction considered with carboplatin as elderly patients may have reduced renal function, more severe myelosuppression and neuropathy.
Refer to PACLitaxel, CARBOplatin drug monograph(s) for additional details of adverse effects.
|
Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
|
Refer to PACLitaxel, CARBOplatin drug monograph(s) for additional details.
-
Monitor INR in patients receiving warfarin; warfarin dosage adjustment may be required.
-
Monitor closely with nephrotoxic and ototoxic drugs (ie. aminoglycosides) due to additive effects.
-
Monitor closely with phenytoin; phenytoin dose adjustment may be required.
-
Avoid if possible, or caution with radiation; may increase the risk of radiation pneumonitis.
Refer to PACLitaxel, CARBOplatin drug monograph(s) for additional details.
Administration
Paclitaxel:
-
In order to minimize patients’ exposure to DEHP leaching from PVC bags or sets, use polyolefin or polypropylene infusion bags and polyethylene-lined administration sets (with a 0.22 micron in-line filter).
-
Dilute in 500-1000 mL Normal Saline or 5% Dextrose, in a final concentration of 0.3-1.2 mg/mL and infuse over 3 hours.
-
Extended infusion of paclitaxel is not recommended as primary prophylaxis to reduce paclitaxel IRs.
-
Excessive shaking, agitation, or vibration may induce precipitation and should be avoided.
-
Precipitation may rarely occur with infusions longer than 3 hours.
Carboplatin:
-
Mix in 100mL to 250mL bag (5% Dextrose or Normal Saline); infuse IV over 15 to 60 minutes.
-
There is insufficient evidence that routine prophylaxis with extended infusion reduces IR rates.
-
Incompatible with sets, needles or syringes containing aluminum – leads to precipitation and loss of potency.
-
Protect from light.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications
-
Patients with a history of severe hypersensitivity to platinum-containing compounds, paclitaxel or other drugs formulated in Cremophor EL (polyethoxylated castor oil)
-
Patients with pre-existing, severe renal impairment
-
Patients with severe myelosuppression or bleeding tumours
Warnings/Precautions
-
Patients who have received extensive prior treatment, have poor performance status and those over 65 years of age
-
Patients with abnormal renal function or who are receiving concomitant nephrotoxic drugs
-
Paclitaxel contains ethanol, and is administered with agents such as antihistamines which cause drowsiness. Patients should be cautioned regarding driving and the use of machinery.
-
Avoid live vaccines. Reduced immunogenicity may occur with the use of inactivated vaccines.
Pregnancy/Lactation
-
Carboplatin and paclitaxel are not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose.
-
Breastfeeding is not recommended.
-
Fertility Effects:
-
Carboplatin: Unknown
-
Paclitaxel: Yes
-
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 before each cycle
-
Liver function tests; baseline and before each cycle
-
Renal function tests (including electrolytes); baseline and before each cycle
-
Blood pressure and pulse; during paclitaxel infusion
-
Opthalmology, if visual impairment; as clinically indicated
-
Clinical assessment of thromboembolism, bleeding, GI effects, infection, musculoskeletal, ototoxicity, neurotoxicity, hypersensitivity and respiratory effects; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
-
INR; baseline and as clinically indicated
-
Continuous cardiac monitoring; during subsequent infusions in patients who developed serious conduction abnormalities
-
Cardiac function tests; baseline and as clinically indicated, especially in patients who are close to the lifetime cumulative dose of anthracyclines / anthracenediones
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Belani CP, Lee JS, Socinski MA, Robert F, Waterhouse D, Rowland K, et al. Randomized phase III trial comparing cisplatin-etoposide to carboplatin-paclitaxel in advanced or metastatic non-small cell lung cancer. Ann Oncol 2005;16:1069-75.
Carboplatin and paclitaxel drug monographs, Cancer Care Ontario.
Kelly K, Crowley J, Bunn P, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: A southwest oncology group trial. J Clin Oncol 2001; 19(13): 3210-8.
Kosmidis PA Kalofonos C, Syrigas K, Skarlos D, Nicolaides C, Bafaloukos D, et al. Paclitaxel and gemcitabine vs. carboplatin and gemcitabine. A multicenter, phase III randomized trial in patients with advanced inoperable Non-small cell lung cancer (NSCLC) [[]abstract]. Proc Am Soc Clin Oncol 2005;23:621.
Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. New Engl J Med 2002; 346:92-8.
Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med 2018;378:2288-301.
August 2021 Modified Rationale and Uses section
Calvert Formula
- AUC = product of serum concentration (mg/mL) and time (min)
- GFR (glomerular filtration rate) expressed as measured Creatinine Clearance or estimated from Serum Creatinine (by Cockcroft and Gault method or Jelliffe method)
(Calvert AH, Newell DR, Gumbrell LA, et al, Carboplatin dosage: Prospective evaluation of a simple formula based on renal function. J Clin Oncol, 1989; 7: 1748-1756)
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.