Cycle length: 14 days. | |||
Drug | Dose and route | Administration | Given on days |
Cetuximab¶ | 500 mg/m2 IV | The appropriate dose should be withdrawn from the vials (supplied in a concentration of 2 mg/mL) and aseptically transferred into an empty sterile IV bag without further dilution. All doses should be infused over 120 minutes.Δ◊ | Days 1 and 15 |
Irinotecan | 180 mg/m2 IV§ | Dilute in 500 mL D5W¥ and administer over 90 minutes after cetuximab; may be given concurrently with leucovorin via y-site connection. | Days 1 and 15 |
Leucovorin‡ | 400 mg/m2 IV | Dilute in 250 mL D5W¥ and administer over two hours; may give concurrent with irinotecan via y-site connection. | Days 1 and 15 |
Fluorouracil (FU), bolus | 400 mg/m2 IV | Slow IV push over five minutes (administer immediately after leucovorin). | Days 1 and 15 |
FU, infusional | 2400 mg/m2 IV† | Dilute in 500 to 1000 mL D5W¥ and administer over 46 hours (begin immediately after FU bolus). To accommodate an ambulatory pump for outpatient treatment, can be administered undiluted (50 mg/mL) or the total dose can be diluted in 100 to 150 mL NS.¥ | Days 1 and 15 |
Pretreatment considerations: | |||
Emesis risk |
| ||
Prophylaxis for infusion reactions |
| ||
Infection prophylaxis |
| ||
Dose adjustment for baseline liver or kidney dysfunction |
| ||
Diarrhea |
| ||
Monitoring parameters: | |||
| |||
| |||
| |||
Suggested dose modifications for toxicity: | |||
Myelotoxicity |
| ||
Diarrhea |
| ||
Dermatologic toxicity |
| ||
Neurologic toxicity |
| ||
Cardiotoxicity |
| ||
Other toxicity |
| ||
If there is a change in body weight of at least 10%, doses should be recalculated. |
ANC: absolute neutrophil count; CBC: complete blood count; DPD: dihydropyrimidine dehydrogenase; D5W: 5% dextrose in water; FDA: US Food and Drug Administration; G-CSF: granulocyte colony stimulating factors; IgE: immunoglobulin; IV: intravenous; NS: normal saline.
¶ The original protocol administered cetuximab 400 mg/m2 loading dose on day 1 followed by maintenance dosing 250 mg/m2 starting on day 8.[1] Results from a nonrandomized phase II trial[5] and a multicenter retrospective analysis[6] suggest that cetuximab at a dose of 500 mg/m2 initially followed by 500 mg/m2 every 2 weeks results in similar plasma concentrations and single-agent activity as does weekly dosing. This regimen is now approved by the FDA, and is easier to administer in conjunction with FOLFIRI.[3]
Δ Cetuximab should be administered with an infusion or syringe pump, using a low protein-binding 0.22-micron inline filter. Do not shake or dilute. Flush line with NS.
◊ A slower infusion rate should be considered in areas with a high incidence of infusion reactions (such as the southeast United States). Refer to UpToDate topics on infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy.
§ A lower initial starting dose of irinotecan may be considered for patients with poor performance status, prior pelvic or abdominal radiotherapy, or increased bilirubin levels.[2] Whether a reduced starting dose is needed in patients who are homozygous for the UGT 1A1*28 allele (Gilbert syndrome) and whether testing for this allele should be carried out prior to starting irinotecan are controversial. Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
¥ Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).
‡ Leucovorin dose is given for d,l-racemic mixture.[7] Use half the dose for LEVOleucovorin (l-leucovorin).
† If there is no grade 1 or worse toxicity 1 in cycles 1 and 2, some clinicians increase the dose to 3000 mg/m2 starting with cycle 3.[1]
Do you want to add Medilib to your home screen?