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IRIN
Gastric / Stomach
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.
| irinotecan | 350 mg /m² | IV | Day 1 |
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Alternative schedule: |
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| irinotecan | 150 mg /m² | IV | Days 1 and 15 |
Standard schedule: REPEAT EVERY 21 DAYS
Alternative schedule: REPEAT EVERY 28 DAYS
Until disease progression or unacceptable toxicity
Moderate
Other Supportive Care:
Also refer to CCO Antiemetic SummaryIrinotecan - Cholinergic adverse effects (early diarrhea):
- Prophylactic atropine may be considered in patients who have experienced cholinergic symptoms
- Diarrhea (including abdominal cramps) may be severe and delayed with Irinotecan; use Loperamide 4mg at the onset of diarrhea, then 2mg q2h until patient is diarrhea-free for 12 hours.
- Loperamide must be provided
Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are in use at some centres.
Patients should not be treated with irinotecan until they have recovered from prior toxicity: platelets ≥ 100 x 109/L, ANC ≥ 1.5 x 109/L, GI toxicity recovered to baseline (without loperamide for at least 24 hours) and all other toxicities to Grade ≤ 1.
Patients with ileus, fever or febrile neutropenia should receive antibiotics.
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
All dose adjustments should be based on the worst preceding toxicity.
| Dose Level | Dose (mg/m2) |
| 0 | 350 |
| -1 | 300 |
| -2 | 250 |
| -3 | 200 |
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Toxicity grade3
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Suggested dose
During treatment course
of Weekly schedule2
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At start of subsequent course1
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3-weekly schedule2
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1
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No change
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No change
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2
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↓ 25mg/m2
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Diarrhea alone – no change
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Hematologic alone – no change
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Other 3: ↓ 50mg/m2
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3
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Omit, then ↓ 25mg/m2 when ≤ grade 2
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↓ 50mg/m2
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4 or febrile neutropenia
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Omit, then ↓ 50mg/m2 when ≤ grade 2
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↓ 50mg/m2
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| Pneumonitis | Hold; investigate and if confirmed, discontinue. | |
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1 Relative to the starting dose used in the previous cycle. Start a new cycle when the parameters below are met.
2 Patients should not be retreated until GI toxicity resolved to baseline (without loperamide for at least 24 h), platelets ≥ 100 x 109/L, ANC ≥ 1.5 x 109/L and and other toxicities recovered to ≤ Grade 1. If no recovery after a 2-week delay, consider discontinuing treatment. 3 Excludes alopecia, anorexia, and fatigue
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Hepatic Impairment
Elimination is decreased in hepatic impairment with increased exposure to SN-38. Patients with bilirubin 1-1.5 x ULN or Gilbert’s syndrome are at an increased risk of myelosuppression.
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Bilirubin 1
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Transaminases
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Irinotecan dose
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22-35 µmoL/L (1-1.5 x ULN) or with Gilbert’s syndrome |
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Monitor closely; may consider dose reduction
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> 35 µmoL/L
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or
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>3 x ULN (without liver metastases) or >5 x ULN (with liver metastases) |
Not recommended.
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1Consider investigating for reversible causes such as biliary obstruction and re-evaluate after stent |
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Renal Impairment
No specific studies, but as the kidney is not a major route of excretion, no adjustment anticipated to be required.
Dosage in the Elderly
Monitor patients ≥ 65 years closely for increased risk of diarrhea. Patients ≥ 70 years of age using the q3w schedule should receive 300mg/m2
Refer to irinotecan drug monograph(s) for additional details of adverse effects
| Very Common ( ≥ 50%) | Common (25-49%) | Less Common (10-24%) |
Uncommon (<10%), but may be |
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Refer to irinotecan drug monograph(s) for additional details
- Azole antifungals are contraindicated with irinotecan (discontinue one week before the first dose of irinotecan)
- Avoid concomitant use of strong CYP3A4 inhibitors and inducers with irinotecan
- Avoid concomitant use of prochlorperazine (on same day of irinotecan treatment), turmeric and azatanavir with irinotecan
Refer to irinotecan drug monograph(s) for additional details
Administration:
- Mix in 500mL bag (D5W-preferred or NS) in a concentration range between 0.12 to 3 mg/mL; infuse IV over 90 minutes
- Do not refrigerate admixtures in NS (may result in precipitation)
- Avoid freezing irinotecan and its admixtures since this may result in drug precipitation.
- Do not admix with other drugs
- Protect from light
- Prior to the initial irinotecan treatment, patients should be given a sufficient supply of loperamide and instructed on its appropriate use.
- Avoid grapefruit, starfruit, Seville oranges, their juices or products during irinotecan treatment
Contraindications:
- Patients with a known hypersensitivity to the product or any of its ingredients
- Irinotecan should not be co-administered with azole antifungals (ketoconazole etc, see Interactions section)
- Avoid in patients with hereditary fructose intolerance since the product contains sorbitol
- Avoid the use of live or live attenuated vaccines
Other Warnings/Precautions:
- Not recommended for use in patients with ECOG performance status 3 or 4, or in patients with moderate or severe increases in bilirubin.
- Carefully monitor and consider dose reduction for elderly patients, patients with poor performance status (= 2), limited marrow reserve, 3rd space accumulation, Gilbert’s syndrome and patients with reduced UGT1A1 activity; they may be more susceptible to the toxic effects of irinotecan.
- Concurrent administration of irinotecan with irradiation is not recommended. Patients with prior pelvic or abdominal irradiation are at an increased risk of severe myelosuppression following irinotecan therapy.
Pregnancy/Lactation:
- Irinotecan is 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.
- Breastfeeding is not recommended.
- Fertility effects unknown
Recommended Clinical Monitoring
- CBC; baseline and before each dose
- Liver function tests; baseline and before each cycle
- Toxicity assessment and rating of diarrhea and other GI effects, cholinergic symptoms, pneumonitis, neurological, bleeding, infection, dehydration, fatigue, pancreatitis, thromboembolism; At each visit
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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 as clinically indicated
Renal function tests; baseline and periodic
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Hironaka S, Ueda S, Yasui H, et al. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013;31(35):4438-44.
Kanat O, Evrensel T, Manavoglu O, et al. Single-agent irinotecan as second-line treatment for advanced gastric cancer. Tumori. 2003 Jul-Aug;89(4):405-7.
Kang JH, Lee SI, Lim do H, et al. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 2012;30:1513-8.
November 2022 Added PEBC guideline link
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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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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