regimen-monograph

CRBPPACLTRAS

Intent

Palliative

Regimen Category

Local

Drugs Used

PACLitaxel , CARBOplatin , trastuzumab

A - Regimen Name

CRBPPACLTRAS Regimen

CARBOplatin-PACLitaxel-Trastuzumab

Disease Site

Breast

Intent

Palliative

Regimen Category

Local : A regimen not widely used by Regional Cancer Centres in this disease site.

Rationale and Uses

Chemotherapy treatment for patients with HER2 positive metastatic breast cancer

B - Drug Regimen

Q3 Weekly Chemotherapy:

PACLitaxel

(Round to nearest 3 mg)

175 mg /m²

IV over 3 hours

Day 1

CARBOplatin

(Round to nearest 10 mg)

AUC 6

Day 1

(Continued on next page)

PLUS

Weekly Trastuzumab Dosing - LOADING Dose

trastuzumab

(Round to nearest 1 mg)

4 mg /kg

IV over 90 minutes

Day 1 - Loading dose (first cycle only)

then Weekly Trastuzumab Dosing - MAINTENANCE Dose

trastuzumab

(Round to nearest 1 mg)

2 mg /kg

IV over 30 minutes (if loading dose is well-tolerated)

Day 8, 15 (first cycle only); Days 1, 8, 15 (starting 2nd cycle)

Q3 Weekly Trastuzumab Dosing - LOADING Dose

trastuzumab

(Round to nearest 1 mg)

8 mg /kg

IV over 90 minutes

Day 1 (Loading dose - first cycle only)

then Q3 Weekly Trastuzumab Dosing - MAINTENANCE Dose

trastuzumab

(Round to nearest 1 mg)

6 mg /kg

IV over 30 minutes (if loading dose is well-tolerated)

Day 1 (starting second cycle)

_{¹Adjust Carboplatin dose to AUC target (using Calvert formula) or in response to platelet counts (using Egorin formula - if previously treated with thrombocytopenic agent), as outlined in "Other Notes" section.}
_{²If delay more than 1 week, the loading dose should be repeated.}

C - Cycle Frequency

REPEAT EVERY 21 DAYS

• Paclitaxel and Carboplatin- For a usual total of 6 cycles, or until disease progression or unacceptable toxicity

• Trastuzumab - Until evidence of stable disease or metastatic progression

D - Premedication and Supportive Measures

Antiemetic Regimen:

Moderate (with Paclitaxel and Carboplatin)

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

Trastuzumab: To prevent recurrence of infusion-associated reactions, acetaminophen and diphenhydramine may be given as pre-medication. Refer to Trastuzumab drug monograph for full details.

E - Dose Modifications

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.

In general, the dose of trastuzumab should be delayed if the chemotherapy cycle is delayed for scheduling convenience; if the delay is > 1 week, loading dose should be repeated.

Dosage with toxicity

Dose levels for paclitaxel: 175 mg/m², 135 mg/m², 110 mg/m²

Toxicity Type / Counts x 10⁹/L		Toxicity Type / Counts x 10⁹/L	Carboplatin¹	Paclitaxel (% previous) ¹
Febrile Neutropenia / Thrombocytopenic bleeding	OR	Grade 4 ANC ≥ 5-7 d or grade 4 platelets	↓ 1 AUC^1,#	↓1 dose level¹
Grade 3 non-hematologic/ related organ			↓ 1 AUC¹	↓1 dose level¹
Toxicity Type / Counts x 10⁹/L		Toxicity Type / Counts x 10⁹/L	Carboplatin¹	Paclitaxel (% previous) ¹
Grade 4 non-hematologic / related organ			Discontinue	Discontinue

_{¹Do not start new cycle until toxicities have recovered to ≤ grade 2, platelets ≥ 100 x 10⁹/L, and ANC ≥ 1.5 x 10⁹/L.}
_{^#Use Egorin formula if isolated thrombocytopenia (See "Other Notes" section)}

Trastuzumab Dosage with Cardiotoxicity:

Product Monograph Recommendations:

Trastuzumab should be held with a fall in LVEF (if LVEF falls ≥10 points from baseline and/or if LVEF falls to < 50%). Repeat LVEF in 3 weeks and consider discontinuing. Discontinue if clinically significant cardiac dysfunction or cardiac failure develops.

Canadian Consensus Guidelines:

Discontinue if symptomatic.

Management of trastuzumab therapy in adjuvant breast cancer patients with asymptomatic decreases in LVEF (Mackey et al 2008):

Relationship of LVEF to Lower Limit of Normal (LLN)	Trastuzumab dose modification based on asymptomatic LVEF decrease from baseline
Relationship of LVEF to Lower Limit of Normal (LLN)	≤ 10 percentage points	10-15 percentage points	≥ 15 percentage points
Within facility’s normal limits	Continue	Continue	Hold and repeat MUGA/ECHO after 4 weeks
1-5% below LLN	Continue ¹	Hold and repeat MUGA/ECHO after 4 weeks ^{1, 2}	Hold and repeat MUGA/ECHO after 4 weeks ^{2, 3}
≥ 6% below LLN	Continue and repeat MUGA/ECHO after 4 weeks ³	Hold and repeat MUGA/ECHO after 4 weeks ^{2, 3}	Hold and repeat MUGA/ECHO after 4 weeks ^{2, 3}

_{¹ Consider cardiac assessment and starting ACEI therapy}
_{² After 2 holds, consider permanent trastuzumab discontinuation}
_{³ Start ACEI therapy and refer to cardiologist}

Trastuzumab Dosage with Other Toxicity:

Toxicity	Action	Comment
Mild hypersensitivity	Decrease infusion rate	May consider re-challenge with premedication
Hypersensitivity (dyspnea, clinically significant hypotension)	Hold	May consider re-challenge with premedication
Pulmonary toxicity, severe or life-threatening hypersensitivity	Discontinue permanently

Paclitaxel Dosage with Hypersensitivity:

For mild symptoms (e.g., mild flushing, rash, pruritus) it is possible 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

Hepatic Impairment

No dose adjustment required for trastuzumab or carboplatin.

For paclitaxel, caution and dose reduction are advised in patients with moderate to severe hepatic impairment. Patients with hepatic impairment may be at risk of toxicity, especially severe myelosuppression. Suggested are:

Bilirubin and/or AST/ALT (3 hour infusion)	PACLItaxel Dose (mg/m²)
2 - 4 x ULN	135
> 4 x ULN	50 or OMIT

Renal Impairment

Creatinine Clearance (mL/min)	PACLItaxel (% previous dose)	CARBOplatin (% previous dose)	trastuzumab (% previous dose)
20 - 50	No adjustment appears to be required.	Use Calvert or Chatelut formula (Refer to "Other Notes" section)	No adjustment appears to be required.
<20	No adjustment appears to be required.	Discontinue	No adjustment appears to be required.

F - Adverse Effects

Refer to trastuzumab, PACLitaxel, CARBOplatin drug monograph(s) for additional details of adverse effects

Most Common Side Effects

Less Common Side Effects, but may be
Severe or Life-Threatening

Headache
Fatigue
Diarrhea (may be severe), mucositis
Musculoskeletal pain
Cardiotoxicity (may be severe)
Infusion-related reaction (may be severe)
Myelosuppression ± infection, bleeding (may be severe)
Neuropathy (may be severe)
Alopecia
Fluid retention
Nausea and vomiting
↑LFTs (may be severe)
Neurotoxicity (including ototoxicity)
Nephrotoxicity (may be severe)
Electrolyte abnormalities

Arterial thromboembolism
Venous thromboembolism
Pancreatitis
GI perforation, obstruction
Pneumonitis
Arrhythmia
Secondary malignancies
Hemolytic uremic syndrome

G - Interactions

Refer to trastuzumab, PACLitaxel, CARBOplatin drug monograph(s) for additional details

H - Drug Administration and Special Precautions

Refer to trastuzumab, PACLitaxel, CARBOplatin drug monograph(s) for additional details

I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

Blood pressure and pulse rate monitoring during paclitaxel infusion, cardiac monitoring with prior arrhythmia
Cardiac assessment, including evaluation of left ventricular function (Echocardiogram or MUGA scan); more frequent with asymptomatic reductions in LVEF; baseline, q3 months during treatment, then q6 months after trastuzumab discontinuation x2 years, also as clinically indicated
CBC; baseline and regular
Liver function tests; baseline and regular
Renal function tests; baseline and regular including electrolytes
Clinical toxicity assessment for flu-like symptoms, pulmonary toxicity, diarrhea, infusion reactions, infection, bleeding, fluid retention, musculoskeletal effects, neurotoxicity, ototoxicity, nausea/vomiting
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Administrative Information

Approximate Patient Visit

First cycle: 7 hours; Subsequent cycles: 6 hours

K - References

Leyland-Jones B, Gelmon K, Ayoub JP, et al. Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol 2003; 21(21):3965-71.

Robert N, Leyland-Jones B, Asmar L, et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 2006;24(18):2786-92.

PEBC Advice Documents or Guidelines

The Role of Trastuzumab (Herceptin) in the Treatment of Women with HER2/neu-Overexpressing Metastatic Breast Cancer

October 2017 Modified drug regimen layout, dose modifications, adverse effects, monitoring

L - Other Notes

Calvert Formula

DOSE (mg) = target AUC X (GFR + 25)

Target AUC of 4 to 6 mg/mL·min (previously treated patients) or 6 to 8 mg/mL·min (previously untreated patients)
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)}

Egorin Formula

Previously Untreated Patients-

DOSE (mg/m²) = 317 {([pre - nadir]/ pre) 100 - 82.1} X (BSA / Cr Cl) + 447

Previously Treated Patients-

DOSE (mg/m²) = 317 {([pre - nadir]/ pre) 100 - 92.4} X (BSA / Cr Cl) + 447

Pre = pretreatment platelet count
Nadir = platelet nadir desired
BSA = Body Surface Area
Cr Cl = Creatinine Clearance

_{(Egorin MJ, Van Echo DA, Tiping SJ, et al, Pharmacokinetics and dosage reduction of carboplatin in patients with impaired renal function. Cancer Res, 1984; 44: 5432-5438)}

Chatelut Formula

Dose (mg) = Target AUC (mg/mL per min) x Carboplatin clearance (Cl_carboplatin in mL/min)

where Cl(carboplatin) equals to:

{ 218 x wt x (1 – {0.00457 x age}) } x { 1 – (0.314 x gender) }
(0.134 x wt) + -----------------------------------------------------------------------------------
Serum creatinine (µmol/L)

_{wt = Weight in kg}
_{Age (years)}
_{Gender (males = 0; females = 1)}
_{Serum Cr = Serum creatinine (µmol/L)}

_{(Chatelut E, Canal P, Brunner V, et al. Prediction of carboplatin clearance from standard morphological and biological patient characteristics. J Natl Cancer Inst 1995;87(8):573-80.)}

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.
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Last Updated: July 27, 2026

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