Cycle length: 4 weeks.
Duration of therapy: 6 cycles. |
| Drug | Dose and route | Administration | Given on days |
| Pegylated liposomal doxorubicin (PLD)* | 50 mg/m2 IV¶ | DiluteΔ in 250 mL or 500 mL 5% dextrose in water (D5W)◊ and administer at an initial rate of 1 mg/min to minimize infusion reactions. Subsequent doses can be given over 60 minutes. | Day 1 |
| Pretreatment considerations: |
| Emesis risk | - LOW.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Vesicant/irritant properties | - PLD is an irritant but it can cause significant tissue damage; avoid extravasation.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| Prophylaxis for infusion reactions | - There is no standard premedication regimen. For flank pain, flushing, shortness of breath, and/or chest tightness, stop the infusion immediately; after resolution, restart treatment at 50% of the original infusion rate.[1] If the reaction occurs again, discontinue PLD; however, most patients are able to tolerate a rechallenge.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
|
| Infection prophylaxis | - Primary prophylaxis with granulocyte colony stimulating factors is not indicated (no febrile neutropenia events were observed in the initial study[1]).
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
|
| Dose adjustment for baseline liver or renal dysfunction | - A lower starting dose of PLD may be needed for patients with preexisting liver impairment.
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents and chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
|
| Cardiac issues | - Doxorubicin is associated with dose-dependent cardiomyopathy, the incidence of which is related to cumulative dose. PLD causes significant cardiomyopathy, but the risk of developing clinical and subclinical cardiotoxicity is less than with native doxorubicin.[2] Assess baseline LVEF prior to initiating therapy.
- Refer to UpToDate topics on cardiotoxicity of anthracycline-like chemotherapy agents.
|
| Monitoring parameters: |
- Monitor for infusion reactions, which may affect as many as 10 to 20% of patients.
|
- Monitor for palmar-plantar erythrodysesthesia and stomatitis.
|
- Monitor cumulative PLD dose. Reassess LVEF periodically during PLD therapy as clinically indicated. In clinical practice, PLD appears to have significantly less cardiotoxicity than unencapsulated anthracyclines, but this does not preclude the need to monitor cardiac function.
|
- CBC with differential should be done at least prior to each dose of PLD and may be needed weekly.
|
- Assess liver function prior to each new cycle of treatment.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Myelotoxicity is uncommon with PLD. Withhold a new cycle of treatment until ANC ≥1500 cells/microL and platelet count ≥75,000/microL.[3] The original trial required a 25% decrease in PLD dose (to 37.5 mg/m2) for grade 4 neutropenia lasting for ≥7 days, and a 50% dose reduction (to 25 mg/m2) for patients with grade 4 neutropenia lasting for ≥7 days plus febrile neutropenia and grade 4 thrombocytopenia.[1] The manufacturer suggests a 25% dose reduction for ANC nadir <500 cells/microL or platelet nadir <25,000/microL, after recovery to ANC ≥1500 cells/microL and platelet count ≥75,000/microL.[3]
|
| Cardiotoxicity | - No formal guidelines exist for PLD discontinuation based upon LVEF function, but guidelines exist for other anthracyclines. The manufacturer recommends that the benefit of continued therapy be carefully weighed against the risk of producing irreversible cardiac damage if test results indicate deterioration in cardiac function during PLD therapy.[3]
|
| Cutaneous toxicity | - Delay new treatment cycle until palmar-plantar erythrodysesthesia is resolved to grade 0 or 1. In the original protocol, for grade 2 toxicity, treatment was delayed by at least one week, and if toxicity persisted for two weeks, the dose was reduced by 25%. For persistent grade 3 or 4 toxicity after two weeks, treatment was discontinued.[1] The United States Prescribing Information suggests a 25% dose reduction for PLD in case of grade 3 or 4 cutaneous toxicity, if it resolves to grade 0 or 1 within two weeks, and treatment discontinuation for grade 2 to 4 cutaneous toxicity that does not resolve after two weeks.[3]
|
| Gastrointestinal toxicity | - Delay new treatment cycle until stomatitis resolved to grade 0 or 1. In this study, dose reductions were allowed for grade 3 or worse mucositis.[1] The United States Prescribing Information suggests a 25% dose reduction for PLD in case of grade 3 or 4 stomatitis, if it resolves to grade 0 or 1 within two weeks, and treatment discontinuation for grade 2 to 4 stomatitis that does not resolve after two weeks.[3]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
