• Monitor BP, HR, respiratory rate, and temperature frequently during administration. Report significant changes.
• Monitor for acute infusion-related reactions consisting of flushing, shortness of breath, facial swelling, headache, chills, chest pain, back pain, chest or throat tightness, fever, tachycardia, pruritus, rash, cyanosis, syncope, bronchospasm, asthma, apnea, and hypotension. If Grade 1–3 infusion reactions occur, ↓infusion rate. If life-threatening infusion reaction occurs, discontinue doxorubicin liposomal. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction.
• Monitor for bone marrow depression. Assess for bleeding (bleeding gums; bruising; petechiae; guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for ↑ fatigue, dyspnea, and orthostatic hypotension.
• Monitor intake and output, and report occurrence of significant discrepancies. Encourage fluid intake of 2000–3000 mL/day. Allopurinol and alkalinization of the urine may be used to ↓ serum uric acid levels and to help prevent urate stone formation.
• Severe and protracted nausea and vomiting may occur as early as 1 hr after therapy and may last 24 hr. Administer parenteral antiemetics 30–45 min prior to therapy and routinely around the clock for the next 24 hr as indicated. Monitor amount of emesis and notify health care provider if emesis exceeds guidelines to prevent dehydration.
• Assess left ventricular cardiac function (echocardiogram) prior to initiation of therapy, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Monitor for development of signs of cardiac toxicity, which may be either acute and transient (ST segment depression, flattened T wave, sinus tachycardia, extrasystoles) or late onset (usually occurs 1–6 mo after initiation of therapy) and characterized by intractable HF (peripheral edema, dyspnea, rales/crackles, weight gain); occurs more frequently in patients receiving a cumulative dose of ≥550 mg/m². Cardiotoxicity is more prevalent in children <2 yr and older adults and when cumulative dose >300 mg/m². Dexrazoxane may be used to prevent cardiotoxicity in patients receiving cumulative doses of >300 mg/m².
• Assess injection site frequently for redness, irritation, or inflammation. Doxorubicin liposomal is an irritant but may infiltrate painlessly even if blood returns on aspiration of infusion needle. Severe tissue damage may occur if doxorubicin liposomal extravasates. If extravasation occurs, stop infusion immediately, restart, and complete dose in another vein. If possible, withdraw 3–5 mL of blood to remove doxorubicin liposomal. Apply ice to site for 15 min four times daily for 3 days. Local infiltration of antidote is not recommended. Delineate the infiltrated area on patient's skin with a felt-tip marker. Elevate for 48 hr above heart level using a sling or stockinette dressing with an observation window cut in the dressing. Avoid pressure or friction. Do not rub the area. Observe for signs of increased erythema, pain, or skin necrosis. If increased symptoms occur, consult a plastic surgeon. After 48 hr, encourage patient to use extremity normally to promote full range of motion.
• Assess oral mucosa frequently for development of stomatitis. ↑ dosing interval and/or ↓ dose is recommended if lesions are painful or interfere with nutrition. For Grade 1: Painless ulcers, erythema, or mild soreness: If no previous Grade 3 or 4 toxicity, no dose adjustment. If previous Grade 3 or 4 toxicity, delay up to 2 wk; then ↓ dose by 25%. For Grade 2: Painful erythema, edema, or ulcers, but can eat: Delay dosing up to 2 wk or until resolved to Grade ≤1. Discontinue therapy if no resolution after 2 wk. If resolved to Grade ≤1 within 2 wk: if no previous Grade 3 or 4 stomatitis, resume therapy at previous dose; if previous Grade 3 or 4 toxicity, ↓ dose by 25%. For Grade 3: Painful erythema, edema, or ulcers, and cannot eat: Delay dosing up to 2 wk or until resolved to Grade ≤1. ↓ dose by 25% and return to original dose interval. If no resolution after 2 wk, discontinue therapy. For Grade 4: Requires parenteral or enteral support: Delay dosing up to 2 wk or until resolved to Grade ≤1. ↓ dose by 25% and return to original dose interval. If no resolution after 2 wk, discontinue therapy.
• Continue to assess oral mucosa regularly during and for ≥6 yr for ulceration or any discomfort; may indicate secondary oral cancer.
• Monitor for skin toxicity with prolonged use; HFS usually occurs after 6 wk of treatment and consists of swelling, pain, and erythema of the hands and feet. This may progress to desquamation but usually regresses after 2 wk. In severe cases, modification and delay of future doses of doxorubicin liposomal may be necessary. For Grade 1: Mild erythema, swelling, or desquamation not interfering with daily activities: If no previous Grade 3 or 4 HFS, no dose adjustment. If previous Grade 3 or 4 HFS, delay dose up to 2 wk; ↓ dose by 25%. For Grade 2: Erythema, desquamation, or swelling interfering with, but not precluding normal physical activities; small blisters or ulcerations less than 2 cm in diameter: Delay dosing up to 2 wk or until resolved to Grade ≤1. Discontinue therapy if no resolution after 2 wk. If resolved to Grade ≤1 within 2 wk: if no previous Grade 3 or 4 HFS, continue treatment at previous dose; if previous Grade 3 or 4 toxicity, ↓ dose by 25%. For Grade 3: Blistering, ulceration, or swelling interfering with walking or normal daily activities; cannot wear regular clothing: Delay dosing up to 2 wk or until resolved to Grade ≤1; ↓ dose by 25%. Discontinue therapy if no resolution after 2 wk. For Grade 4: Diffuse or local process causing infectious complications, or a bedridden state or hospitalization: Delay dosing up to 2 wk or until resolved to Grade ≤1; ↓ dose by 25%. Discontinue therapy if no resolution after 2 wk.

Lab Test Considerations:

• Obtain negative pregnancy test before starting therapy. Monitor CBC and differential prior to and periodically during therapy. The WBC nadir occurs 10–14 days after administration, and recovery usually occurs by the 21st day. Thrombocytopenia and anemia may also occur. ↑ dosing interval and/or ↓ dose is recommended if ANC <1000 cells/mm³ and/or platelet count <50,000 cells/mm³. If ANC 1500–1900 cells/mm³ and platelets 75,000–150,000 cells/mm³ (Grade 1), resume treatment with no dose ↓. If ANC 1000–<1500 cells/mm³ and platelets 50,000–<75,000 cells/mm³ (Grade 2), wait until ANC >1500 cells/mm³and platelets >75,000 cells/mm³; then redose with no dose ↓. If ANC 500–999 cells/mm³ and platelets 25,000–<50,000 cells/mm³ (Grade 3), wait until ANC >1500 cells/mm³and platelets >75,000 cells/mm³; then redose with no dose ↓. If ANC <500 cells/mm³and platelets <25,000 cells/mm³ (Grade 4), wait until ANC >1500 cells/mm³and platelets >75,000 cells/mm³; then ↓ dose by 25% or continue full dose with prophylactic granulocyte growth factor.
  • Recommended modifications of doxorubicin liposomal when administered with bortezomib.If fever ≥38°C and ANC <1000 cells/mm³, withhold dose for this cycle if before Day 4; ↓ dose by 25% if after Day 4 of previous cycle. If on any day of drug administration after Day 1 of each cycle: Platelet count <25,000 cells/mm³ or hemoglobin <8 g/dL or ANC <500 cells/mm³, withhold dose for this cycle if before Day 4; ↓ dose by 25% if after Day 4 of previous cycle AND if bortezomib is reduced for hematologic toxicity. If Grade 3 or 4 nonhematologic drug related toxicity, do not dose until recovered to Grade <2; then ↓ dose by 25%.
  • Monitor renal (BUN and serum creatinine) and hepatic (AST, ALT, LDH, and serum bilirubin) function prior to and periodically during therapy. Dose ↓ required for bilirubin >1.2 mg/dL or serum creatinine >3 mg/dL.
  • May ↑ serum and urine uric acid concentrations.