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.
CRBPGEMC(W)
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.
For the treatment of metastatic breast cancer.
REPEAT EVERY 21 DAYS
Until disease progression, no evidence of further response, or unacceptable toxicity.
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
Dose on Day 1 of Cycle:
|
Worst Toxicity in Previous Cycle |
Gemcitabine |
Carboplatin |
||
|
Non-Hematologic (related organ) |
|
Hematologic (counts x 109/L)
|
% Full Dose1 |
% Full Dose1 |
|
Grade 3 |
or |
Febrile neutropenia, thrombocytopenic bleeding, ANC < 0.5 for > 5 days or < 0.1 for > 3 days, or platelets < 25 |
75%2 |
75%3 |
|
Grade 4
|
|
|
Consider discontinuing, or ↓ to 50-75%4 |
Consider discontinuing, or ↓ to 50-75%4 |
|
Day 8 holds in > 1 cycle
|
75% |
100% |
||
|
Pneumonitis |
Hold and investigate. If confirmed, discontinue |
Hold and investigate. If confirmed, discontinue. |
||
|
Hemolytic Uremic Syndrome (HUS), |
|
|
Discontinue |
Consider Discontinue |
|
Stevens-Johnson syndrome (SJS), |
|
|
Discontinue |
Consider Discontinue |
|
1 do not retreat until ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and toxicity ≤ grade 2. 2 if toxicity recurs after gemcitabine dose reduction, omit day 8 gemcitabine. 3 use Egorin formula if isolated thrombocytopenia. 4 if the reduced dose is tolerated well, a re-increase to 75% may be considered for the following cycle |
||||
Dose on Day 8 of Cycle:
|
Toxicity on Day 8 of cycle |
Day 8 dose |
|||||
|
Non-hematologic (related organ) |
|
Hematologic |
Gemcitabine (% Full Dose) |
Carboplatin (% Full Dose) |
||
|
ANC (x 109/L) |
|
Platelets (x 109/L) |
||||
|
≤ grade 2 |
and |
≥ 1.5 |
and |
≥ 100 |
100% |
100% |
|
≤ grade 2 |
and |
1.0-1.49 |
and/or |
75-99 |
↓ to 50% |
↓ to 50% |
|
grade 3 or 4 |
and/or |
< 1.0 |
and/or |
< 75 |
Omit |
Omit |
|
Pneumonitis |
|
- |
|
- |
Discontinue |
Consider Discontinue |
Hepatic Impairment
|
Bilirubin
|
|
AST/ALT
|
Gemcitabine
(% previous dose)
|
Carboplatin
(% previous dose)
|
|
1-2 x ULN
|
And/or
|
<2 x ULN
|
100%
|
100%
|
|
2-4 x ULN
|
2-5 x ULN
|
Caution
|
100%
|
|
|
> 4 x ULN |
> 5 x ULN
|
Caution, consider ↓
|
Caution, consider ↓
|
Renal Impairment
|
CrCl (mL/min)
|
Gemcitabine
(% previous dose)
|
Carboplatin
(% previous dose)
|
|
> 60
|
100%
|
Use Calvert formula
|
|
40-60
|
100%
|
|
|
20-40
|
Caution
|
|
|
< 20
|
Consider discontinuing or ↓
|
Discontinue
|
Dosage in the Elderly
Caution should be exercised and dose reduction considered for carboplatin as elderly patients may have more severe myelosuppression and neuropathy.
Gemcitabine clearance is lower in the elderly but no dose adjustment necessary.
Refer to gemcitabine, 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 CARBOplatin, gemcitabine drug monograph(s) for additional details
- Caution concurrent use of nephrotoxic and ototoxic medications due to additive effects with carboplatin.
- Carboplatin may cause a decrease in phenytoin levels; monitor closely and increase phenytoin dose if necessary.
- Monitor INR closely with concurrent warfarin as both gemcitabine and carboplatin may increase INR and bleeding risk.
Refer to CARBOplatin, gemcitabine 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.
Gemcitabine:
- May dilute reconstituted drug in normal saline for IV infusion, resulting in a minimum final concentration of at least 0.1 mg/mL.
- Infuse over 30 minutes through free-flowing IV. Infusion time beyond 60 minutes has been shown to increase toxicity.
Contraindications:
- Patients who have a hypersensitivity to these drugs or other platinum-containing compounds
- Patients with severe renal impairment, severe myelosuppression or bleeding tumours
Other Warnings/Precautions:
- Patients with abnormal renal function or who are receiving concomitant nephrotoxic drugs
- Patients with impaired hepatic function, including concurrent liver metastases or a previous history of hepatitis, alcoholism or liver cirrhosis
- Patients who have received extensive prior treatment, have poor performance status and those over 65 years of age
- Patients receiving concurrent radiation while receiving full dose gemcitabine should be closely monitored for reactions
- Potentially life-threatening esophagitis and pneumonitis, particularly in patients receiving large volumes of radiotherapy have been observed.
Pregnancy and Lactation:
- Carboplatinn and gemcitabine 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 (for women of childbearing potential).
- Breastfeeding is not recommended.
- Fertility effects: Probable (gemcitabine)
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 treatment
- Liver function tests; baseline and before each cycle
- Renal function tests and electrolytes (including magnesium); baseline and before each cycle
- Clinical toxicity assessment (including flu-like symptoms, fatigue, rash, edema, GI, pulmonary, neurotoxicity, infection, bleeding, ototoxicity); at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- INR for patients receiving warfarin; Baseline and as clinically indicated
- Urinalysis; Baseline and as clinically indicated
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Carboplatin and gemcitabine drug monographs, Cancer Care Ontario.
Chan D, Yeo WL, Tiemsim Cordero M, et al. Phase II study of gemcitabine and carboplatin in metastatic breast cancers with prior exposure to anthracyclines and taxanes. Invest New Drugs. 2010 Dec;28(6):859-65.
Laessig D, Stemmler HJ, Vehling-Kaiser U, et al. Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer. Oncology. 2007;73(5-6):407-14.
Maisano R, Zavettieri M, Azzarello D, et al. Carboplatin and gemcitabine combination in metastatic triple-negative anthracycline- and taxane-pretreated breast cancer patients: a phase II study. J Chemother. 2011 Feb;23(1):40-3.
Nagourney RA, Flam M, Link J, et al. Carboplatin plus gemcitabine repeating doublet therapy in recurrent breast cancer. Clinical Breast Canacer. 2008;8(5): 432-5.
Yardley DA, Burris HA 3rd, Simons L, et al. A phase II trial of gemcitabine/carboplatin with or without trastuzumab in the first-line treatment of patients with metastatic breast cancer. Clin Breast Cancer. 2008 Oct;8(5):425-31.
December 2018 Updated regimen name to reflect the weekly schedule.
Carboplatin dosing by BSA is not recommended as it does not take into account of the patient’s renal function and/or desired platelet nadir, which may result in overdosing (i.e. patients with poor renal function) or underdosing (i.e. with above average renal function). Several methods have been proposed for calculating carboplatin doses, considering the area under the curve (AUC) and its subsequent hematologic toxicity, and also the direct relationship between glomerular filtration and carboplatin clearance.
Calvert Formula: (Most commonly used method)
Dose (mg) = Target AUC (mg/mL per min) x [CrCl† (mL/min) + 25]
(See "References - Appendix" section)
†Note: Older laboratory methods of measuring creatinine overestimated low levels of creatinine. Serum creatinine measured by the Isotope Diluted Mass Spectrometry (IDMS) method accurately measures creatinine, producing potentially lower levels than would have been reported with older methods; thus the lower limits of normal are significantly lower than the limits in the past. Using the IDMS method, if the creatinine levels are low, the calculated creatinine clearance (CrCl) and the estimated GFR may be substantially higher than the normal GFR when formally measured using radioisotopic methods. The Calvert formula was developed using the older methodology for creatinine measurement, and using it uncapped may result in certain patients with low serum creatinine levels appearing to have a very high GFR, and thus receiving very high and inappropriate carboplatin doses with resulting toxicity.
To avoid toxicity, FDA recommends capping the carboplatin dose for a desired AUC. The maximum dose is based on a GFR estimate that is capped at 125 mL/min for patients with normal renal function:
Maximum Carboplatin Dose (mg) = target AUC (mg/mL per min) x (125 mL/min + 25)
(See FDA communication on carboplatin dosing)
Egorin Formula: Takes into account of BSA, creatinine clearance, desired platelet nadir and pretreatment platelet count. (See "References - Appendix" section)
Chatelut Formula:
Dose (mg) = Target AUC (mg/mL per min) x Carboplatin clearance (mL/min)
(See "References - Appendix" section)
The Chatelut formula should not be used in pediatric or hemodialysis patients.
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.