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.
CRBPPACL+BEVA
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 selected patients with unresectable advanced, metastatic, or recurrent non-squamous non-small cell lung cancer who have good performance status (ECOG 0 or 1), with no brain metastases, hemoptysis, history of bleeding diathesis or coagulopathy.
PACLitaxel | 175 to 200 mg /m² | IV over 3 hours | Day 1 |
followed by : |
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CARBOplatin | AUC 5 | IV | Day 1 |
Adjust Carboplatin dose to AUC target (using Calvert formula) as outlined in "Other Notes" section. |
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bevacizumab | 15 mg /kg | IV over 90 minutes* | Day 1 |
(This drug is not currently publicly funded for this regimen and intent) | |||
(*if tolerated next infusion can be given over 60 minutes; can thereafter be given over 30 minutes as maintenance dose)
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For carboplatin, paclitaxel, for a usual total of 4 to 6 cycles. Bevacizumab monotherapy may be continued therafter (not currently publicly funded).
REPEAT EVERY 21 DAYS
Until disease progression or unacceptable toxicity.
Moderate + NK1 antagonist (Carboplatin AUC ≥ 5)
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
Also refer to CCO Antiemetic Recommendations.
Doses should be modified according to the protocol by which the patient is being treated.
Bevacizumab should not be initiated until hypertension is controlled and wound healing has occurred, dental evaluation has been performed and any major dental procedures completed. May consider prophylaxis for patients who have had prior mild hypersensitivity reactions and who are continuing on treatment.
Dosage with toxicity
Hematologic Toxicities
Refer to Appendix 6 for general recommendations.
Hypersensitivity reaction
Reaction
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Paclitaxel
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Bevacizumab
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Mild (e.g.
mild flushing, rash, pruritus)
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Possible to complete the infusion under close supervision
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May stop the infusion. Give diphenhydramine and corticosteroid if indicated. Resume infusion at slower rate under close supervision.
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Moderate (e.g.
moderate rash, flushing, mild dyspnea, chest discomfort, mild hypotension)
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Stop the infusion and give diphenhydramine 25-50 mg IV and methylprednisolone 125 mg IV.
Once symptoms have resolved, resume 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.
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Stop the infusion and hold for remainder of the day. Give diphenhydramine and corticosteroid, or other supportive measures if indicated.
Consider discontinuing bevacizumab. If re-challenge on a different treatment day, use slower infusion rate.
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Reaction (continued) | Paclitaxel | Bevacizumab |
Severe (e.g.
one or more of: respiratory distress requiring treatment, generalized urticaria, angioedema, hypotension requiring therapy)
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Stop the paclitaxel infusion and give diphenhydramine and methylprednisolone as above. Use epinephrine or bronchodilators if indicated.
Discontinue. Do not re-challenge.
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Stop the infusion and give diphenhydramine and corticosteroid. Use epinephrine or bronchodilators if indicated.
Discontinue. Do not re-challenge.
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Non-hematologic Toxicities:
Any grade
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Grade 3
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Grade 4
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Bevacizumab action
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Paclitaxel/
carboplatin action
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Uncontrollable hypertension
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HOLD
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CONSIDER HOLD or DISCONTINUE |
Delayed wound healing; Surgery
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Proteinuria ≥2g/24 hours* |
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Wound dehiscence
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DISCONTINUE
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CONSIDER HOLD or DISCONTINUE
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Tracheo-esophageal fistula, other non-GI fistulae; GI perforation
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Fistula
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Nephrotic syndrome; non recovery of proteinuria ≥2g/24 hours
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Hypertension
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Severe Hypersensitivity
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RPLS
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Bleeding
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Bleeding
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Arterial thromboembolism
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Venous thromboembolism
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Symptomatic cardiac failure
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Any grade | Grade 3 | Grade 4 | Bevacizumab action |
Paclitaxel/
carboplatin action
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Hemoptysis > 2.5mL; Intracranial bleeding | DISCONTINUE | CONSIDER HOLD or DISCONTINUE | ||
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Neuropathy
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No change
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Hold until ≤ grade 2, then reduce by 20%
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Neutropenia ≥ 5 days
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Febrile Neutropenia
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Paclitaxel/carboplatin related toxicity
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*may restart when < 2g/24hrs
Hepatic Impairment
Bilirubin
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AST/ALT
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Paclitaxel
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2-4 x ULN
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or
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2-4 x ULN
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↓ to 135mg/m2
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> 4 ULN
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or
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> 4 x ULN
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OMIT
or
give maximum dose of 50mg/m2
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- No adjustment appears necessary for carboplatin or bevacizumab.
Renal Impairment
Creatinine clearance (mL/min)
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Paclitaxel
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Carboplatin
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Bevacizumab
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20-50
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No adjustment appears necessary
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Use Calvert or Chatelut formula (refer to other notes section)
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No information found; no adjustment appears necessary
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<20
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Discontinue
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Refer to PACLitaxel, CARBOplatin, bevacizumab 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 PACLitaxel, CARBOplatin, bevacizumab drug monograph(s) for additional details
Refer to PACLitaxel, CARBOplatin, bevacizumab 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
- Baseline and regular liver and renal function tests
- CBC; baseline and before each cycle
- Dental evaluation before starting treatment
- Monitor blood pressure during paclitaxel infusion and every 2-3 weeks during bevacizumab therapy and more frequently in patients who develop hypertension.
- Baseline and regular dipstick urinalysis; 24 hour urine collection is recommended for patients with a 2+ or greater urine dipstick
- Clinical toxicity assessment (including hypersensitivity, musculoskeletal, perforation, fistula, GI symptoms, hemorrhage, infection, ONJ, thromboembolism, wound healing, hypertension, neurologic and cardiac effects); at each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Cardiac function tests (Echo, RNA and/or MUGA scans) especially in patients who are close to the lifetime cumulative dose of anthracyclines/anthracenediones; baseline and as clinically indicated
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Carboplatin, paclitaxel and bevacizumab drug monographs, Cancer Care Ontario.
Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non–small-cell lung cancer. JCO 2004; 22: 2184-2191.
Sandler A, Gray R, Perry MC, et al. Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. NEJM 2006; 355(24): 2542.
May 2019 Updated emetic risk category
Calvert Formula
DOSE (mg) = target AUC X (GFR + 25)
- 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)
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.