regimen-monograph

GEMCIRIN

Intent

Palliative

Regimen Category

Evidence-Informed

Drugs Used

gemcitabine , irinotecan

A - Regimen Name

GEMCIRIN Regimen

Gemcitabine-Irinotecan

Disease Site

Unknown Primary

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 metastatic cancer of unknown primary. Patients with adenocarcinoma, poorly differentiated adenocarcinoma, poorly differentiated carcinoma, or poorly differentiated squamous carcinoma were included in a small phase III clinical trial. This regimen produced significantly less myelosuppression than CRBPPAC+ETOP(PO), but had more diarrhea and more frequent discontinuation for toxicity. Response rates, progression-free survival and 2-year survival were similar.

B - Drug Regimen

gemcitabine

1000 mg /m²

Day 1 and Day 8

irinotecan

100 mg /m²

Day 1 and Day 8

C - Cycle Frequency

REPEAT EVERY 21 DAYS

For a usual total of 4-6 cycles, unless disease progression or unacceptable toxicity.

D - Premedication and Supportive Measures

Antiemetic Regimen:

Moderate

Other Supportive Care:

Irinotecan - Unless contraindicated, atropine 0.25-1mg IV/SC may be used for cholinergic adverse effects (early diarrhea) Use loperamide 4mg at the onset of diarrhea, then 2mg q2h until patient is diarrhea-free for 12 hours
Patients with ileus, fever or febrile neutropenia should receive antibiotics

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.

Patients should not be re-treated with irinotecan until recovery (to baseline) from GI toxicity (without loperamide for at least 24 hours) has occurred, platelets ≥ 100 x 10⁹/L, and ANC ≥ 1.5 x 10⁹/L. All dose adjustments should be based on the worst preceding toxicity.

Patients with ileus, fever or febrile neutropenia should receive antibiotics.

Do not use in patients with ECOG PS of 3 or 4, nor in patients with moderate or severe increases in bilirubin.

Consider a reduction in the starting dose described below for elderly patients (≥ 70 years), patients with prior abdominal or pelvic irradiation, patients with a poor performance status (ECOG of 2), patients with mild increases in bilirubin (including Gilbert’s syndrome), patients homozygous for UGT1A1*28 allele or patients with a history of myelosuppression with previous treatment.

Dosage with toxicity

Worst Toxicity / Counts (x 10⁹/L) in PRIOR CYCLE		Worst Toxicity / Counts (x 10⁹/L) on TREATMENT DAY	irinotecan (% previous dose)	gemcitabine (% previous dose)
		ANC > 1.5 or Platelet > 100	100%
		ANC 1 to 1.5 or Platelets 75-100	75%
		ANC < 1 or platelets < 75	Hold until ANC > 1 and Platelets > 100, then 75%
Febrile neutropenia, or Thrombocytopenic bleeding, or Platelets < 25, or ANC <0.5 for ≥5-7 d	Or		Hold *, then 75%
Grade 3 or 4 diarrhea			Hold until ≤ grade 1, then 75% for suspect drug(s)
Grade 3 related organ / non-hematologic			Hold then *75% for suspect drug(s)
Grade 4 related organ / non-hematologic; Delay > 3 weeks due to toxicity; Pneumonitis; Hemolytic uremic syndrome; Stevens-Johnson syndrome; Toxic epidermal necrolysis; Capillary Leak Syndrome			Discontinue suspect drug(s)

*Do not treat until toxicities have recovered to ≤ grade 2 (grade 0-1 (or baseline) for diarrhea - off loperamide), platelets > 100 x 10⁹/L, and ANC > 1.5 x 10⁹/L.

Hepatic Impairment

Transaminases	Bilirubin	Irinotecan	Gemcitabine
	1-1.5 X ULN or Gilbert's	Consider ↓	No change
> 3 X ULN*	2-4 X ULN	Omit	Caution; consider dose adjustment
	> 4 XULN	Omit	Consider dose adjustment
^{* or 5 X ULN with liver metastases}

Renal Impairment

Creatinine Clearance (mL/min)	Irinotecan	Gemcitabine
10 – 50	No adjustment required	Use with caution; no specific recommendation found. Close monitoring for occurrence of hemolytic uremic syndrome is required.
< 10	No adjustment required

F - Adverse Effects

Refer to irinotecan, gemcitabine drug monograph(s) for additional details of adverse effects

Most Common Side Effects	Less Common Side Effects, but may be Severe or Life-Threatening
Myelosuppression ± infection, bleeding (may be severe) Fatigue, flu-like symptoms Musculoskeletal pain Rash (may be severe) Edema Proteinuria Nausea or vomiting Diarrhea (both early and late; may be severe) Abdominal pain/cramps Constipation Anorexia Mucositis Dizziness, insomnia Headache ↑ LFTs (may be severe) Alopecia	Hemolytic-uremic syndrome Arrhythmia Cardiotoxicity Hypersensitivity Arterial/venous thromboembolism Pancreatitis Pneumonitis/ARDS Capillary leak syndrome GI obstruction, perforation Renal failure Vasculitis Tumour lysis syndrome

G - Interactions

Refer to irinotecan, gemcitabine drug monograph(s) for additional details

H - Drug Administration and Special Precautions

Refer to irinotecan, gemcitabine drug monograph(s) for additional details

I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

CBC; baseline and at each visit
Liver function tests; baseline and regular
Renal function tests; baseline and regular
Clinical assessment of diarrhea and other GI effects, rash, cholinergic symptoms, flu-like symptoms, pneumonitis, neurological, bleeding, infection, dehydration, fatigue, pancreatitis, thromboembolism; routine
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

Blood glucose, especially in patients with diabetes; baseline and regular

J - Administrative Information

Approximate Patient Visit

2.5 hours

Pharmacy Workload (average time per visit)

28.517 minutes

Nursing Workload (average time per visit)

41.667 minutes

K - References

Gemcitabine and irinotecan drug monographs, Cancer Care Ontario.

Greco FA, Rodriguez GI, Shaffer DW, et al. Carcinoma of unknown primary site: sequential treatment with paclitaxel/carboplatin/etoposide and gemcitabine/irinotecan: a Minnie Pearl Cancer Research Network phase II trial. Oncologist 2004;9(6):644-52.

Hainsworth JD, Spigel DR, Clark BL, et al. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J 2010;16(1):70-5.

Hainsworth JD, Spigel DR, Raefsky EL, et al. Combination chemotherapy with gemcitabine and irinotecan in patients with previously treated carcinoma of an unknown primary site: a Minnie Pearl Cancer Research Network Phase II trial. Cancer. 2005;104(9):1992-7.

October 2017 Replaced regimen category with evidence-informed

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
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Last Updated: July 27, 2026

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