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.
CISPGEMC
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.
| CISplatin | 75 mg /m² | IV | Day 1 |
| gemcitabine | 1000 mg /m² | IV | Days 1, 8 and 15 |
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Alternative schedule: |
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| CISplatin | 75 mg /m² | IV | Day 1 |
| gemcitabine | 1000 mg /m² | IV | Days 1 and 8 |
Standard schedule: REPEAT EVERY 28 DAYS
Alternative schedule: REPEAT EVERY 21 DAYS
Until disease progression or unacceptable toxicity, usually up to 6 cycles due to cumulative cisplatin toxicity
High (D1)
Low (D8, 15)
Other Supportive Care:
Also refer to CCO Antiemetic Recommendations.
Standard regimens for Cisplatin premedication and hydration should be followed. Refer to local guidelines
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
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Worst toxicity in previous cycle
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Gemcitabine (% previous dose)
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Cisplatin (% previous dose)
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Grade 4 febrile neutropenia or thrombocytopenia
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75%
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75%
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Grade 2 neurotoxicity/ototoxicity/nephrotoxicity
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No change
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75%
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Grade 3 or 4 neurotoxicity/ototoxicity/nephrotoxicity
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No change
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Hold for current cycle; consider discontinuing
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Other grade 3 non-hematologic related organ toxicity
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75%
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75%
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Day 8 or day 15 holds in > 1 cycle
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75%
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No change
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Grade 4 non-hematologic related organ, pneumonitis, hemolytic uremic syndrome, SJS/TEN, CLS, PRES, severe hypersensitivity
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Discontinue
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Discontinue
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Toxicity on Day 8 or Day 15 of cycle
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|
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Non-hematologic
(related organ)
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Hematologic
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Gemcitabine
(% Full Dose)
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AGC
(x 106/L)
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Platelets
(x 106/L)
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≤ grade 2
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and
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> 1000
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and
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> 100,000
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100%
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≤ grade 2
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and
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500-1000
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or
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50,000-100,000
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Consider Omit,
or ↓ to 50-75%
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Grade 3 or 4
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or
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< 500
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or
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< 50,000
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Omit, ↓ to 75% at restart (if applicable) for non-hematologic toxicity
|
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Pneumonitis, HUS, SJS, TEN, CLS
|
|
-
|
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-
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Discontinue
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Hepatic Impairment
|
Bilirubin
|
|
AST/ALT
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Gemcitabine
(% previous dose)
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Cisplatin
(% previous dose)
|
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1-2 x ULN
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and/ or
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< 2 x ULN
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100%
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100%
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2-4 x ULN
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2-5 x ULN
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Caution
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100%
|
|
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> 4 x ULN
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> 5 x ULN
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Caution, consider ↓
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Caution, consider ↓
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Renal Impairment
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Creatinine Clearance (mL/min)
|
Gemcitabine
(% previous dose)
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Cisplatin
(% previous dose)
|
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> 60
|
100%
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100%
|
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>45-60
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Caution
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75%
|
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30-45
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Caution
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50%
|
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< 30
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Consider discontinuing or ↓
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Discontinue
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Dosage in the Elderly
CISplatin: Geriatric patients may be at higher risk of developing nephrotoxicity, ototoxicity/neurotoxicity or hematologic adverse effects with cisplatin.
gemcitabine: Clearance is lower in the elderly but no dose adjustment necessary.
Refer to gemcitabine, CISplatin drug monograph(s) for additional details of adverse effects
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Most common side effects
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Less common side effects, but may be severe or life-threatening
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· Myelosuppression +/- infection and bleeding (may be severe)
· Fatigue, flu-like symptoms
· Musculoskeletal pain
· Nausea, vomiting
· ↑ LFTs (may be severe)
· Neurotoxicity
· Ototoxicity
· Nephrotoxicity (may be severe)
· Electrolyte abnormalities
· Diarrhea
· Rash
· Edema
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· Cardiotoxicity, arrhthymia
· Arterial thromboembolism
· Hemolysis
· Hemolytic uremic syndrome
· Vasculitis
· Hemolysis
· Pneumonitis
· Capillary leak syndrome
· Seizures
· PRES
· Hypersensitivity
· Secondary malignancy
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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
- Electrolytes, including magnesium, sodium, potassium, phosphate and calcium; baseline and regular
- Liver function tests; baseline and regular
- Renal function tests; baseline and regular
- Clinical toxicity assessment (infection, bleeding, nausea/vomiting, neurotoxicity, ototoxicity, GI and CNS effects); regular
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Audiogram; baseline and periodic
- INR for patient receiving warfarin; baseline and regular
- Urinalysis; baseline and regular
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Cisplatin and gemcitabine drug monographs, Cancer Care Ontario.
Culine S, Lortholary A, Voigt JJ, et al; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82.
Gross-Goupil M, Fourcade A, Blot E, et al. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7.
Isik M, Seker MM, Odabas H, et al. Gemcitabine and cisplatin in patients with carcinoma of unknown primary site. Med Oncol 2011;28(2):591-6.
May 2019 Updated emetic risk category
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.
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