CRBPPACL

Language English

Regimen Monograph References:

Carboplatin and paclitaxel drug monographs, Cancer Care Ontario.

Kim R, Byer J, Fulp WJ et al. Carboplatin and Paclitaxel Treatment Is Effective in Advanced Anal Cancer. Oncology 2014;87:125-32.

Cancer Type: Gastrointestinal Anus Type of Content: Regimen Regimen Code:

CRBPPACL

Intent: Palliative Regimen Category:

Evidence-Informed

Drugs Used: PACLitaxel CARBOplatin Regimen Monograph Name:

CRBPPACL_GI_ANU_P

Regimen Monograph Body:

Regimen Monograph

A - Regimen Name

CRBPPACL Regimen

PACLitaxel-CARBOplatin

Disease Site

Gastrointestinal - Anus

Intent

Palliative

Regimen Category

Evidence-Informed :

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.

Rationale and Uses

For treatment of advanced squamous cell carcinoma of the anal canal.

B - Drug Regimen

PACLitaxel

175 mg /m²

Day 1

CARBOplatin

AUC 5 to 6*

Day 1

_{*Adjust Carboplatin dose to AUC target (using Calvert formula) as outlined in "Other Notes" section.}

C - Cycle Frequency

REPEAT EVERY 21 DAYS

Until disease progression or unacceptable toxicity, usually up to 6 cycles due to cumulative carboplatin toxicity

D - Premedication and Supportive Measures

Antiemetic Regimen:

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.

E - Dose Modifications

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)
0	175
-1	135
-2	110

Worst Toxicity (Counts x 10⁹/L)	Carboplatin	Paclitaxel
ANC < 1.5 for > 7 days	Hold¹; No change upon restart	Hold¹, then Consider adding G-CSF and continue current dose, if appropriate OR ↓ 1 dose level
ANC < 0.5 for ≥ 7 days or Febrile Neutropenia	Hold¹; ↓ 1 AUC upon restart	Hold¹, then Consider adding G-CSF and continue current dose, if appropriate OR ↓ 1 dose level
Platelets < 25 or Thrombocytopenic bleeding	Hold¹; ↓ 1 AUC upon restart	Hold¹; ↓ 1 dose level upon restart
Grade 2 neuropathy	No change	Omit or consider ↓ 1 dose level
Grade 3 neuropathy	No change	Omit or ↓ 1 dose level
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.

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
Grade	Carboplatin / Paclitaxel	Carboplatin^#	Paclitaxel
1 or 2	Stop or slow the infusion rate. Manage the symptoms. Restart: After symptom resolution, restart with pre-medications ± reduced infusion rate.	Consider pre-medications* and infusing at a reduced infusion rate prior to re-challenge. May consider adding oral montelukast ± oral acetylsalicylic acid.	Consider re-challenge with pre-medications and at a reduced infusion rate. After 2 subsequent IRs, consider replacing with a different taxane. Give intensified pre-medications and reduce the infusion rate. May consider adding oral montelukast ± oral acetylsalicylic acid.
3 or 4	Stop treatment. Aggressively manage symptoms.	Re-challenge is discouraged, especially if vital signs have been affected. Consider desensitization if therapy is necessary.	Re-challenge is discouraged, especially if vital signs have been affected. Consider desensitization if therapy is necessary. There is insufficient evidence to recommend substitution with another taxane at re-challenge. High cross-reactivity rates have been reported.

^#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	No change	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.

F - Adverse Effects

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

Alopecia (rarely permanent)
Peripheral neuropathy (may be severe)
Myelosuppression ± infection, bleeding (may be severe)
Musculoskeletal pain
Nausea, vomiting

Hypersensitivity
Abnormal electrolytes
Nephrotoxicity (may be severe)
Fatigue

Edema
Mucositis
Constipation
Diarrhea (may be severe)
↑ LFTs
Hearing impairment
ECG changes

Arrhythmia, cardiac failure
Arterial / venous thromboembolism
Rash
Radiation recall reaction
GI obstruction / perforation
Hemolytic uremic syndrome
Pancreatitis
Injection site reaction
Secondary malignancy
Autonomic, cranial neuropathy
Encephalopathy
Cystoid macular edema
Seizure
Pneumonitis
Visual disturbances

G - Interactions

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.

H - Drug Administration and Special Precautions

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

I - 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.

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

J - Administrative Information

Approximate Patient Visit

5-6 hours

Pharmacy Workload (average time per visit)

30.383 minutes

Nursing Workload (average time per visit)

59.833 minutes

K - References

Carboplatin and paclitaxel drug monographs, Cancer Care Ontario.

Kim R, Byer J, Fulp WJ et al. Carboplatin and Paclitaxel Treatment Is Effective in Advanced Anal Cancer. Oncology 2014;87:125-32.

August 2020 Updated infusion reaction information in Premedication and Supportive Measures, Dose Modifications and Drug Administration and Special Precautions sections; updated Adverse Effects section; removed Egorin formula

L - Other Notes

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)

_{(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)}

M - Disclaimer

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.

Regimen Info Sheet Name: CRBPPACL (BR-GY-other) Regimen Info Sheet Body:

CRBPPACL Treatment

This handout gives general information about this cancer treatment.

You will learn:

who to contact for help
what the treatment is
how it is given
what to expect while on treatment

This handout was created by Ontario Health (Cancer Care Ontario) together with patients and their caregivers who have also gone through cancer treatment. It is meant to help support you through your cancer treatment and answer some of your questions.

This information does not replace the advice of your health care team. Always talk to your health care team about your treatment.

Who do I contact if I have questions or need help?

My cancer health care provider is: _____________________________________________

During the day I should contact: _______________________________________________

Evenings, weekends and holidays: _____________________________________________

This page gives general information about this cancer treatment.

You will learn:

who to contact for help
what the treatment is
how it is given
what to expect while on treatment

This information was created by Ontario Health (Cancer Care Ontario) together with patients and their caregivers who have also gone through cancer treatment. It is meant to help support you through your cancer treatment and answer some of your questions.

This information does not replace the advice of your health care team. Always talk to your health care team about your treatment.

What is this treatment?

CRBPPACL is the code name of your cancer treatment regimen. CRBPPACL is used to treat different types of cancers including breast and ovarian cancer.

A regimen is a combination of medications to treat cancer.

This regimen name is made up of one or more letters from the names of the 2 medications in your treatment.

Here are the name(s) of the medication(s) in this regimen:

CRBP = CaRBoPlatin

PACL = PACLitaxel (also called Taxol®)

For most people, treatment lasts 18 weeks. The treatment is divided into 6 cycles. Each cycle is 3 weeks long.

Here is a picture of the schedule for CRBPPACL treatment:

Cycle 1 

CRBPPACL 

(3 weeks)

Cycle 2

CRBPPACL 

(3 weeks)

Cycle 3

CRBPPACL 

(3 weeks)

Cycle 4

CRBPPACL 

(3 weeks)

Cycle 5

CRBPPACL 

(3 weeks)

Cycle 6

CRBPPACL 

(3 weeks)

During each 3-week cycle, you will have CRBPPACL treatment on day 1 at the hospital.

Each cycle looks like this:

Day 1

Treatment Day:

Go to the hospital for CRBPPACL treatment

CRBPPACL Treatment

Remember To:

Tell your health care team about all of the other medications you are taking.
Keep taking other medications that have been prescribed for you, unless you have been told not to by your health care team.

You will have a blood test to check for hepatitis B before starting treatment. See the Hepatitis B and Cancer Medications pamphlet for more information.

How is this treatment given?

The medication(s) in your treatment are given through an IV (injected into a vein) at the hospital.

Your health care team may suggest that you get a PICC line or a Port-a-Cath.

These are special IV’s used to give medicines and fluids into larger veins.
A PICC or Port-a-Cath can be safer for some medications that can cause reactions
when given through an IV in your hand.
If you have a PICC or Port-a-Cath you do not need an IV (needle) put into your arm
every time you come for treatment.

Talk to your healthcare team about the benefits and risks of a PICC or a Port-a-Cath to see if one of these options is right for you.

You will have a blood test before each treatment cycle to make sure it is safe for you to get treatment.

What other medications are given with this treatment?

To Prevent Nausea and Vomiting

You will be given medications to help prevent nausea (feeling like throwing up) and vomiting (throwing up) before they start.

These are called anti-nausea medications and include medications such as ondansetron (Zofran®), granisetron (Kytril®), aprepitant (Emend®), or others.

To Prevent Allergic Reaction

You will be given medications before your treatment to help prevent allergic reactions before they start.

There are different types of medications to stop allergic reactions. They are called:
- antihistamines (such as diphenhydramine or Benadryl®)
- analgesics/antipyretics (such as acetaminophen or Tylenol®)
- H2 blockers (such as ranitidine or famotidine)
- corticosteroids (such as prednisone)

DO this while on treatment

DO tell your health care team about any other medical conditions that you have such as hearing problems, heart, liver or kidney problems, or any allergies.

DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures.

DO tell your health care team if you have any new pain, numbness or tingling of your hands or feet. This is especially important if you are having trouble doing tasks (like doing up buttons, writing, walking) or if you have severe pain or numbness.

DO talk to your health care team about your risk of getting other cancers and heart problems after this treatment.

DO consider asking someone to drive you to and from the hospital on your treatment days. You may feel drowsy or dizzy after your treatment.

DO NOT do this while on treatment

Stop Icon

DO NOT take any other medications, such as vitamins, over-the-counter (non-prescription) drugs, or natural health products without checking with your health care team.

DO NOT start any complementary or alternative therapies, such as acupuncture or homeopathic medications, without checking with your health care team.

DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.

DO this while on treatment

Check Mark Icon

DO tell your health care team about any other medical conditions that you have such as hearing problems, heart, liver or kidney problems, or any allergies.

DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures.

DO tell your health care team if you have any new pain, numbness or tingling of your hands or feet. This is especially important if you are having trouble doing tasks (like doing up buttons, writing, walking) or if you have severe pain or numbness.

DO talk to your health care team about your risk of getting other cancers and heart problems after this treatment.

DO consider asking someone to drive you to and from the hospital on your treatment days. You may feel drowsy or dizzy after your treatment.

DO NOT do this while on treatment

Stop Icon

DO NOT take any other medications, such as vitamins, over-the-counter (non-prescription) drugs, or natural health products without checking with your health care team.

DO NOT start any complementary or alternative therapies, such as acupuncture or homeopathic medications, without checking with your health care team.

DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.

Will this treatment interact with other medications or natural health products?

Yes, the medications in this regimen can interact with other medications, vitamins, foods and natural health products. Interactions can make the treatment not work as well or cause severe side effects.

Tell your health care team about all of your:

prescription and over-the-counter (non-prescription) medications
natural health products such as vitamins, herbal teas, homeopathic medicines, and other supplements

Check with your health care team before starting or stopping any of them.

If you take seizure medications (such as phenytoin), your health care team may monitor your blood levels closely and may change your dose.

If you are taking a blood thinner (such as warfarin), your health care team may need extra blood tests and may change your dose.

Talk to your health care team BEFORE taking or using these:

Anti-inflammatory medications such as ibuprofen (Advil^® or Motrin^®), naproxen (Aleve^®) or Aspirin^®
Over-the-counter products such as dimenhydrinate (Gravol^®)
Natural health products such as St. John’s Wort
Supplements such as vitamin C
Grapefruit juice
Alcoholic drinks
Tobacco
All other drugs, such as marijuana or cannabis (medical or recreational)

What should I do if I feel unwell, have pain, a headache or a fever?

Always check your temperature to see if you have a fever before taking any medications for fever or pain (such as acetaminophen (Tylenol^®) or ibuprofen (Advil^®)).
- Fever can be a sign of infection that may need treatment right away.
- If you take these medications before you check for fever, they may lower your temperature and you may not know you have an infection.

How to check for fever:

Keep a digital (electronic) thermometer at home and take your temperature if you feel hot or unwell (for example, chills, headache, mild pain).

You have a fever if your temperature taken in your mouth (oral temperature) is:
- 38.3°C (100.9°F) or higher at any time
OR
- 38.0°C (100.4°F) or higher for at least one hour.

If you do have a fever:

Try to contact your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away.
Ask your health care team for the Fever pamphlet for more information.

If you do not have a fever but have mild symptoms such as headache or mild pain:

Ask your health care team about the right medication for you. Acetaminophen (Tylenol^®) is a safe choice for most people.

Talk to your health care team before you start taking ibuprofen (Advil^®, Motrin^®), naproxen (Aleve^®) or ASA (Aspirin^®), as they may increase your chance of bleeding or interact with your cancer treatment.

Talk to your health care team if you already take low dose aspirin for a medical condition (such as a heart problem). It may still be safe to take.

How will this treatment affect sex, pregnancy and breast feeding?

Talk to your health care team about:

How this treatment may affect your sexual health

How this treatment may affect your ability to have a baby, if this applies to you

This treatment may harm an unborn baby. Tell your health care team if you or your partner are pregnant, become pregnant during treatment, or are breastfeeding.

If there is any chance of pregnancy happening, you and your partner together must use 2 effective forms of birth control at the same time while you are on treatment. Talk to your health care team about which birth control options are best for you, and how long you should use them after your last treatment dose.
Do not use hormonal birth control (such as birth control pills), unless your health care team told you that they are safe. Talk to your health care team about the safest birth control for you.
Do not breastfeed while on this treatment. Talk to your health care team about how long to wait before you start breastfeeding after your last treatment dose, if this applies to you.

What are the side effects of this treatment?

The following table lists side effects that you may have when getting CRBPPACL treatment. The table is set up to list the most common side effects first and the least common last. It is unlikely that you will have all of the side effects listed and you may have some that are not listed.

Read over the side effect table so that you know what to look for and when to get help. Refer to this table if you experience any side effects while on CRBPPACL treatment.

Very Common Side Effects (50 or more out of 100 people)
Side effects and what to do	When to contact health care team
Hair thinning or loss What to look for? Your hair may become thin or fall out during or after treatment. In most cases, your hair will grow back after treatment. The texture or colour may change. In very rare cases, hair loss may be permanent. What to do? Use a gentle soft brush. Do not use hair sprays, bleaches, dyes and perms.	Talk to your health care team if this bothers you
Neuropathy (Tingling, numb toes or fingers) What to look for? Numbness or tingling of your fingers and toes may happen after starting your treatment. It can also happen to other parts of your body. Sometimes it can be painful and feel like a burning sensation, which may be severe. What to do? Talk to your health care team if you have symptoms of neuropathy. Numbness and tingling may slowly get better after your treatment ends. In rare cases, it may continue long after treatment ends. If you continue to have bothersome symptoms, talk to your health care team for advice.	Talk to your health care team, especially if you have trouble doing tasks like doing up buttons, writing, moving, or if you have severe pain or numbness
Low neutrophils (white blood cells) in the blood (neutropenia) (May be severe) When neutrophils are low, you are at risk of getting an infection more easily. Ask your health care team for the Neutropenia (Low white blood cell count) pamphlet for more information. What to look for? If you feel hot or unwell (for example if you have chills or a new cough), you must check your temperature to see if you have a fever. Do not take medications that treat a fever before you take your temperature (for example, Tylenol® (acetaminophen), or Advil® (ibuprofen)). Do not eat or drink anything hot or cold right before taking your temperature. You have a fever if your temperature taken in your mouth (oral temperature) is: 38.3°C (100.9°F) or higher at any time OR 38.0°C (100.4°F) or higher for at least one hour. What to do? If your health care team has told you that you have low neutrophils: Wash your hands often to prevent infection. Check with your health care team before getting any vaccines, surgeries, medical procedures or visiting your dentist. Keep a digital thermometer at home so you can easily check for a fever. If you have a fever: If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you must get emergency medical help right away.	If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you MUST get emergency medical help right away.
Low platelets in the blood (May be severe) When your platelets are low, you are at risk for bleeding and bruising. Ask your health care team for the Low Platelet Count pamphlet for more information. What to look for? Watch for signs of bleeding: bleeding from your gums unusual or heavy nosebleeds bruising easily or more than normal black coloured stools (poo) or blood in your stools (poo) coughing up red or brown coloured mucus dizziness, constant headache or changes in your vision heavy vaginal bleeding red or pink coloured urine (pee) What to do? If your health care team has told you that you have low platelets: Tell your pharmacist that your platelet count may be low before taking any prescriptions or over-the-counter medication. Check with your healthcare team before you go to the dentist. Take care of your mouth and use a soft toothbrush. Try to prevent cuts and bruises. Ask your health care team what activities are safe for you. Your treatment may have to be delayed if you have low platelets. Your health care team may recommend a blood transfusion. If you have signs of bleeding: If you have a small bleed, clean the area with soap and water or a saline (saltwater) rinse. Apply pressure for at least 10 minutes. If you have bleeding that does not stop or is severe (very heavy), you must get emergency medical help right away.	Talk to your health care team if you have any signs of bleeding. If you have bleeding that doesn’t stop or is severe (very heavy), you MUST get emergency help right away.
Mild joint, muscle pain or cramps What to look for? New pain in your muscles or joints, muscle cramps, or feeling achy. What to do? Take pain medication (acetaminophen or opioids such as codeine, morphine, hydromorphone, oxycodone) as prescribed. Read the above section: "What should I do if I feel unwell, have pain, a headache or a fever?" before taking acetaminophen (Tylenol®), ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or Aspirin. These medications may hide an infection that needs treatment or they may increase your risk of bleeding. Rest often and try light exercise (such as walking) as it may help. Ask your health care team for the Pain pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe
Nausea and vomiting What to look for? Nausea is feeling like you need to throw up. You may also feel light-headed. You may feel nausea within hours to days after your treatment. What to do? To help prevent nausea: It is easier to prevent nausea than to treat it once it happens. If you were given anti-nausea medication(s), take them as prescribed, even if you do not feel like throwing up. Drink clear liquids and have small meals. Get fresh air and rest. Do not eat spicy, fried foods or foods with a strong smell. Limit caffeine (like coffee, tea) and avoid alcohol. If you have nausea or vomiting: Take your rescue (as-needed) anti-nausea medication(s) as prescribed. Ask your health care team for the Nausea & Vomiting pamphlet for more information. Talk to your health care team if: nausea lasts more than 48 hours vomiting lasts more than 24 hours or if it is severe	Talk to your healthcare team if nausea lasts more than 48 hours or vomiting lasts more than 24 hours or if it is severe

Common Side Effects (25 to 49 out of 100 people)
Side effects and what to do	When to contact health care team
Allergic reaction What to look for? Fever, itchiness, rash, swollen lips, face or tongue, chest and throat tightness. It may happen during or shortly after your treatment is given to you and may be severe. What to do? Tell your nurse right away if you feel any signs of allergic reaction during or just after your treatment. Talk to your health care team for advice if you have a mild skin reaction.	Get emergency medical help right away for severe symptoms
Too much or too little salt in your body What to look for? Muscle spasms, cramping, weakness, twitching, or convulsions. Irregular heartbeat, confusion or blood pressure changes. What to do? Get emergency medical help right away for severe symptoms.	Get emergency medical help right away for severe symptoms
Liver problems Your health care team may check your liver function with a blood test. Liver changes do not usually cause any symptoms. What to look for? Rarely, you may develop yellowish skin or eyes, unusually dark pee or pain on the right side of your belly. This may be severe. What to do? If you have any symptoms of liver problems, get emergency medical help right away.	Get emergency medical help right away
Kidney problems (May be severe) Your health care team may check for proteins in your urine (pee) and your kidney function regularly with a blood test. You may have blood in your urine. What to look for? Swelling in your hands, ankles, feet or other areas of your body. Weight gain that is not normal for you. Pain in your lower back. Muscle twitches and cramps or itchiness that won't go away. Nausea (feeling like you need to throw up) and vomiting. Changes in urination (peeing) such as less urine than usual. What to do? If you have any of these signs, talk to your health care team or go to your closest emergency department. To prevent kidney infections: Drink at least 6 to 8 cups (2 litres) of water or other liquids per day unless your health care team has told you to drink more or less. When you feel the need to pee, go as soon as possible. Do not wait or hold in the pee.	Get emergency medical help right away
Fatigue What to look for? Feeling of tiredness or low energy that lasts a long time and does not go away with rest or sleep. What to do? Be active. Aim to get 30 minutes of moderate exercise (you are able to talk comfortably while exercising) on most days. Check with your health care team before starting any new exercise. Pace yourself, do not rush. Put off less important activities. Rest when you need to. Ask family or friends to help you with things like housework, shopping, and child or pet care. Eat well and drink at least 6 to 8 glasses of water or other liquids every day (unless your health care team has told you to drink more or less). Avoid driving or using machinery if you are feeling tired. Ask your health care team for the Fatigue pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe

Less Common Side Effects (10 to 24 out of 100 people)
Side effects and what to do	When to contact health care team
Mild swelling What to look for? You may have mild swelling or puffiness in your arms and/or legs. Rarely, this may be severe. What to do? To help prevent swelling: Eat a low-salt diet. If you have swelling: Wear loose-fitting clothing. For swollen legs or feet, keep your feet up when sitting.	Talk to your health care team if it does not improve or if it is severe
Mouth sores What to look for? Round, painful, white or gray sores inside your mouth that can occur on the tongue, lips, gums, or inside your cheeks. In more severe cases they may make it hard to swallow, eat or brush your teeth. They may last for 3 days or longer. What to do? To help prevent mouth sores: Take care of your mouth by gently brushing and flossing regularly. Rinse your mouth often with a homemade mouthwash. To make a homemade mouthwash, mix 1 teaspoonful of baking soda and 1 teaspoonful of salt in 4 cups (1L) of water. Do not use store-bought mouthwashes, especially those with alcohol, because they may irritate your mouth. If you have mouth sores: Avoid hot, spicy, acidic, hard or crunchy foods. Your doctor may prescribe a special mouthwash to relieve mouth sores and prevent infection. Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow. Ask your health care team for the Oral Care (Mouth Care) pamphlet for more information.	Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow
Constipation What to look for? Having bowel movements (going poo) less often than normal. Small hard stools (poo) that look like pellets. The need to push hard and strain to have any stool (poo) come out. Stomach ache or cramps. A bloated belly, feeling of fullness, or discomfort. Leaking of watery stools (poo). Lots of gas or burping. Nausea or vomiting. What to do? To help prevent constipation: Try to eat more fiber rich foods like fruits with skin, leafy greens and whole grains. Drink at least 6 to 8 cups of liquids each day unless your health care team has told you to drink more or less. Be active. Exercise can help to keep you regular. If you take opioid pain medication, ask your health care team if eating more fibre is right for you. To help treat constipation: If you have not had a bowel movement in 2 to 3 days you may need to take a laxative (medication to help you poo) to help you have regular bowel movements. Ask your health care team what to do. Ask your health care team for the Constipation Pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe
Diarrhea (May be severe) What to look for? Loose, watery, unformed stool (poo) that may happen days to weeks after you get your treatment. What to do? If you have diarrhea: Take anti-diarrhea medication if your health care team prescribed it or told you to take it. Do not eat foods or drinks with artificial sweetener (like chewing gum or ‘diet’ drinks), coffee and alcohol. Eat many small meals and snacks instead of 2 or 3 large meals. Drink at least 6 to 8 cups of liquids each day, unless your health care team has told you to drink more or less. Talk to your health care team if you can’t drink 6 to 8 cups of liquids each day when you have diarrhea. You may need to drink special liquids with salt and sugar, called Oral Rehydration Therapy. Talk to your health care team if your diarrhea does not improve after 24 hours of taking diarrhea medication or if you have diarrhea more than 7 times in one day. Ask your health care team for the Diarrhea pamphlet for more information.	Talk to your health care team if no improvement after 24 hours of taking diarrhea medication or if severe (more than 7 times in one day)
Change in your hearing What to look for? Not being able to hear as well as before. New noise or ringing sounds in your ears. Changes in hearing usually go away over time. In some rare cases they may be permanent. What to do? Tell your health care team if you have any of these symptoms. Your health care team may need to change your medication.	Talk to your health care team as soon as possible
Heart problems What to look for? You may have an irregular heartbeat, shortness of breath, chest pain or fainting spells. Swelling in your legs, ankles and belly. Sharp pain in the centre or left side of the chest (often worsens when taking a deep breath). Extreme tiredness that prevents you from exercising or doing normal activities. What to do? Get emergency medical help right away.	Get emergency medical help right away

Other rare, but serious side effects are possible with this treatment.

If you have any of the following, talk to your cancer health care team or get emergency medical help right away:

chest pain, fainting (passing out), shortness of breath
pain and swelling or hardening of a vein in your arm or leg
new coughing, coughing up blood or breathing problems
seizures, trouble speaking, difficulty moving your arms or legs or weakness on one side of your body
any severe belly pain
redness/rash at the site of injection or in areas where you’ve previously received radiation
any changes to your vision

For more information on how to manage your symptoms ask your health care provider, or visit: https://www.cancercareontario.ca/symptoms.

Notes

December 2023 Updated "How will this treatment affect sex, pregnancy and breast feeding?" section

For more links on how to manage your symptoms go to www.cancercareontario.ca/symptoms.

The information set out in the medication information sheets, regimen information sheets, and symptom management information(for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.

A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace 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.

Regimen Info Sheet (English):

CRBPPACL BR-GY-other.pdf Regimen Monograph (English):

CRBPPACL_GI_ANU_P.pdf Global Date: Tuesday, August 4, 2020 Info Sheet Date: Tuesday, January 16, 2024 AddThis: Universal Date: 2024-01-16 00:00:00 Monograph Status: Null Info Sheet Status: Null Info Sheet Status 10: Hidden Info Sheet Status 11: Hidden Info Sheet Status 12: Hidden Info Sheet Status 13: Hidden Info Sheet Status 14: Hidden Info Sheet Status 15: Hidden Info Sheet Status 16: Hidden Info Sheet Status 17: Hidden Info Sheet Status 18: Hidden Info Sheet Status 19: Hidden Info Sheet Status 2: Hidden Info Sheet Status 20: Hidden Info Sheet Status 3: Hidden Info Sheet Status 4: Hidden Info Sheet Status 5: Hidden Info Sheet Status 6: Hidden Info Sheet Status 7: Hidden Info Sheet Status 8: Hidden Info Sheet Status 9: Hidden QBP Drug Name: NULL NULL QBP Type: NULL NULL QBP Description: NULL NULL Revision Summary:
Patient Info Sheet EN: (Every 3 weeks) - Updated "How will this treatment affect sex, pregnancy and breast feeding?" section
Patient Info Sheet FR: (Every 3 weeks) - Updated "How will this treatment affect sex, pregnancy and breast feeding?" section (Mise à jour de la section « Comment ce traitement influe-t-il sur la vie sexuelle, la grossesse et l’allaitement? ») Info sheet Public Title: Every 3 weeks Regimen Info Sheet (French):

CRBPPACL BR-GY-other pour le patient.pdf