regimen-monograph

CRBPPACL

Intent

Adjuvant

Regimen Category

Evidence-Informed

Drugs Used

PACLitaxel , CARBOplatin

A - Regimen Name

CRBPPACL Regimen

PACLitaxel-CARBOplatin

Disease Site

Gynecologic - Uterine Sarcoma
Sarcoma - Uterine

Intent

Adjuvant

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.

B - Drug Regimen

PACLitaxel

175 mg /m²

Day 1

CARBOplatin

AUC 4 to 6

Day 1

_{Adjust 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.}

C - Cycle Frequency

REPEAT EVERY 21 DAYS

For a usual total of 6 cycles unless disease progression or unacceptable toxicity occurs

D - Premedication and Supportive Measures

Antiemetic Regimen:

Moderate

Other Supportive Care:

Also refer to CCO Antiemetic Summary

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, and
ranitidine 50mg IV 30 minutes before paclitaxel.

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.

Dosage with toxicity

Suggested Dose Levels:

Dose Level	Carboplatin	Paclitaxel (mg/m²)
0	AUC 6	175
-1	AUC 5	160
-2	AUC 4	135

Worst toxicity in previous cycle	Carboplatin (% previous dose)	Paclitaxel (% previous dose)*
Febrile neutropenia; Grade 4 ANC ≥ 5-7 days OR	No change	Consider adding G-CSF and continue current dose OR ↓ 1 dose level
Neutropenia as defined above AND platelets < 100 for > 7d, grade 4 thrombocytopenia OR thrombocytopenic bleeding	↓ 1 dose level	Consider adding G-CSF and continue current dose OR ↓ 1 dose level
Grade 3 neurotoxicity OR other toxicity	↓ 1 dose level	↓ 1 dose level
Grade 4 neurotoxicity OR other toxicity;	Discontinue	Discontinue
Any grade cystoid macular edema	No Change	Hold and investigate; refer patient promptly to an ophthalmic examination. Discontinue if confirmed

_{*Patients should not be retreated with paclitaxel until neutrophils ≥ 1.5 x 10⁹/L and platelet counts ≥ 100 x 10⁹/L and other toxicity has recovered to ≤ grade 2}

Hepatic Impairment

No dose adjustment required for carpboplatin.

Bilirubin	Dose
1. If Bilirubin 2-4 x ULN	Give MAXIMUM dose of Paclitaxel 135mg/m²
2. If Bilirubin > 4 x ULN	OMIT Paclitaxel dose or Give MAXIMUM dose of Paclitaxel 50mg/m²

Renal Impairment

As creatinine clearance changes, adjust dosage of Carboplatin using the Calvert Formula. See "Other Notes" section.
Modification for paclitaxel not required.

Dosage in the Elderly

Paclitaxel: No adjustment required, but elderly patients are more at risk for severe toxicity.

Carboplatin: Caution should be exercised and dose reduction considered as elderly patients may have 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
Neuropathy (may be severe)
Musculoskeletal pain
Myelosuppression ± infection, bleeding
Nausea, vomiting

Hypersensitivity
Abnormal electrolytes
Increased LFTs (may be severe)
Diarrhea
Nephrotoxicity (may be severe)

Edema
Mucositis
Fatigue
Ototoxicity
ECG changes

Arterial thromboembolism
Venous thromboembolism
Cystoid macular edema
GI perforation, obstruction
Hemolytic uremic syndrome
Pancreatitis
Pnemonitis
Typhlitis

G - Interactions

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

Caution and monitor with nephrotoxic drugs (i.e. aminoglycosides)
Caution and monitor INR in patients receiving warfarin
Caution and monitor phenytoin levels in patients receiving phenytoin
Caution and monitor with CYP3A4 and 2C8 inhibitors and inducers
Avoid if possible, or caution with radiation given increased risk of radiation pneumonitis

H - Drug Administration and Special Precautions

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

Administration

Carboplatin:

Mix in 100mL to 250mL bag (5% Dextrose or Normal Saline); infuse IV over 15 to 60 minutes.
Incompatible with sets, needles or syringes containing aluminum – leads to precipitation and loss of potency.
Protect from light.

Paclitaxel:

Use non-PVC equipment, including 0.22 micron in-line filter, in order to minimize patients’ exposure to DEHP leaching from PVC bags or sets; infuse over 3 hours.
Dilute in 500-1000 mL Normal Saline or 5% Dextrose, in a final concentration of 0.3-1.2 mg/mL.
Excessive shaking, agitation, or vibration may induce precipitation and should be avoided.
Precipitation may rarely occur with infusions longer than 3 hours.

Contraindications:

Patients who have a hypersensitivity to platinum-containing compounds, paclitaxel or other drugs formulated in Cremophor EL (polyethoxylated castor oil)
Patients with severe renal impairment
Patients with severe baseline neutropenia (<1.5 x 10⁹/L; < 1 x 10⁹/L for patients with AIDS-related Kaposi’s) or bleeding tumours

Other warnings/precautions:

Patients with abnormal renal function or who are receiving concomitant nephrotoxic drugs
Patients who have received extensive prior treatment, have poor performance status and those over 65 years of age
Severe arrhythmias may occur during infusion; patients should be appropriately managed and undergo continuous ECG monitoring during subsequent infusions. Congestive heart failure (including LVEF decrease) has been reported in patients who have received other chemotherapy agents, especially anthracyclines.
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.

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
Blood pressure and pulse rate monitoring during paclitaxel infusion, cardiac monitoring with prior arrhythmia
Liver function tests; baseline and regular
Renal function tests; baseline and regular, including electrolytes
Clinical assessment of thromboembolism, bleeding, nausea and vomiting, infection, musculoskeletal, ototoxicity, neurologic (sensory), hypersensitivity and flu-like symptoms; regular
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

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.

Powell MA, Filiaci VL, Rose PG, et al. Phase II evaluation of paclitaxel and carboplatin in the treatment of carcinosarcoma of the uterus: a Gynecologic Oncology Group study. J Clin Oncol 2010;28(16):2727-31.

Otsuki A, Watanabe Y, Nomura H, et al. Paclitaxel and carboplatin in patients with completely or optimally resected carcinosarcoma of the uterus: a phase II trial by the Japanese Uterine Sarcoma Group and the Tohoku Gynecologic Cancer Unit. Int J Gynecol Cancer 2015;25(1):92-7.

January 2018 Removed palliative intent

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)}

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)}

M - Disclaimer

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Last Updated: July 21, 2026

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