Doxil: FDA approves new indication for doxorubicin liposome injection

Key Points

New indication

Doxil
Doxorubicin liposome injection
Anthracycline topoisomerase inhibitor approved in combination with bortezomib for the treatment of multiple myeloma
Doxorubicin is thought to work by binding DNA and inhibiting nucleic acid synthesis. This agent in combination with bortezomib was approved on May 17, 2007, for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received ≥1 prior therapy.

Efficacy. The efficacy of doxorubicin liposome injection in combination with bortezomib for the treatment of multiple myeloma was evaluated in a randomized, open-label, international, multicenter study. The study enrolled 646 patients who had not received previous bortezomib treatment and whose disease had progressed during or after ≥1 prior therapy. Patients were randomized 1:1 to receive either doxorubicin liposome injection 30 mg/m² as a 1-hour intravenous infusion administered on Day 4 after bortezomib 1.3 mg/m² intravenous bolus on Days 1, 4, 8, and 11 or bortezomib alone, also at a dose of 1.3 mg/m² intravenous bolus on Days 1, 4, 8, and 11; treatment was administered to patients every 3 weeks. Patients were treated for ≤8 cycles until disease progression or unacceptable toxicity occurred; however, patients who maintained a response were allowed to receive further treatment. Patients in each treatment arm received a median of 5 treatment cycles (range, 1–18). The primary end point was time to progression (TTP). The combination arm had demonstrated significant improvement in TTP (TTP, 282 d; 95% CI, 250–338) versus the bortezomib-alone arm (TTP, 197 d; 95% CI, 170–217; HR=0.55; 95% CI, 0.43–0.71; P<.0001) at the time of the interim analysis, so patients in the bortezomib-alone arm were allowed to switch to combination therapy. Survival continued to be followed, but the survival data are not yet mature.

Dosing. For the treatment of patients with multiple myeloma, bortezomib should be administered at a dose of 1.3 mg/m² as intravenous bolus on Days 1, 4, 8, and 11 every 3 weeks; doxorubicin liposome injection 30 mg/m² should be administered as a 1-hour intravenous infusion on Day 4 after bortezomib treatment. For the first dose of doxorubicin liposome injection, an initial rate of 1 mg/min should be used to minimize the risk of infusion-related reactions; if no adverse reactions are reported, the infusion rate should be increased to complete drug administration over 1 hour. Treatment should continue for ≤8 cycles until disease progression or unacceptable toxicity occurs. If adverse reactions occur, dosing should be adjusted or delayed; once the dose has been reduced, it should not be increased during later treatment cycles.