The plasma clearance of total doxorubicin from doxorubicin hydrochloride liposome injection was 0.041 L/h/mat a dose of 20 mg/m. Following administration of doxorubicin HCl, the plasma clearance of doxorubicin is 24 to 35 L/h/m.
Doxorubicinol, the major metabolite of doxorubicin, was detected at concentrations of 0.8 to 26.2 ng/mL in the plasma of patients who received 10 or 20 mg/mdoxorubicin hydrochloride liposome injection.
Patients With AIDS-Related Kaposi’s Sarcoma The safety data described is based on the experience reported in 753 patients with AIDS-related Kaposi’s sarcoma (KS) enrolled in four open-label, uncontrolled trials of doxorubicin hydrochloride liposome injection administered at doses ranging from 10 to 40 mg/mevery 2 to 3 weeks. Demographics of the population were: median age 38.7 years (range 24 to 70); 99% male; 88% Caucasian, 6% Hispanic, 4% Black, and 2% Asian/other/unknown. The majority of patients were treated with 20 mg/mof doxorubicin hydrochloride liposome injection every 2 to 3 weeks with a median exposure of 4.2 months (range 1 day to 26.6 months). The median cumulative dose was 120 mg/m(range 3.3 to 798.6 mg/m); 3% received cumulative doses of greater than 450 mg/m.
The safety data described below are from Trial 4, which included 239 patients with ovarian cancer treated with doxorubicin hydrochloride liposome injection 50 mg/monce every 4 weeks for a minimum of four courses in a randomized, multicenter, open-label study. In this trial, patients received doxorubicin hydrochloride liposome injection for a median number of 3.2 months (range 1 day to 25.8 months). The median age of the patients is 60 years (range 27 to 87), with 91% Caucasian, 6% Black, and 3% Hispanic or Other. Table 3 presents the hematologic adverse reactions from Trial 4.
Adverse reactions led to discontinuation of treatment in 5% of patients with AIDS-related Kaposi’s sarcoma and included myelosuppression, cardiac adverse reactions, infusion-related reactions, toxoplasmosis, HFS, pneumonia, cough/dyspnea, fatigue, optic neuritis, progression of a non-KS tumor, allergy to penicillin, and unspecified reasons. Tables 5 and 6 summarize adverse reactions reported in patients treated with doxorubicin hydrochloride liposome injection for AIDS-related Kaposi’s sarcoma in a pooled analysis of the four trials.
The efficacy of doxorubicin hydrochloride liposome injection in combination with bortezomib was evaluated in Trial 6, a randomized, open-label, international, multicenter study in 646 patients who had not previously received bortezomib and whose disease progressed during or after at least one prior therapy. Patients were randomized (1:1) to receive either doxorubicin hydrochloride liposome injection (30 mg/m) administered IV on day 4 following bortezomib (1.3 mg/mIV on days 1, 4, 8 and 11) or bortezomib alone every 3 weeks for up to 8 cycles or until disease progression or unacceptable toxicity. Patients who maintained a response were allowed to receive further treatment. The median number of cycles in each treatment arm was 5 (range 1 to 18).
Retrospective efficacy analyses were performed in two trials that had subsets of patients who received single-agent doxorubicin hydrochloride liposome injection and who were on stable antiretroviral therapy for at least 60 days prior to enrollment and until a response was demonstrated. In one trial, 7 of 17 (40%) patients had a durable response (median duration not reached but was longer than 11.6 months). In the second trial, 4 of 11 patients (40%) on a stable antiretroviral therapy demonstrated durable responses.
Handle and dispose of Doxorubicin Hydrochloride for Injection consistent with recommendations for the handling and disposal of hazardous drugs.
Your doctor will do tests to check the strength of your heart muscle before, during, and after your treatment with doxorubicin hydrochloride for injection.
The median time on study was 5.1 months (range 1 day to 15 months). The median cumulative dose of doxorubicin hydrochloride liposome injection was 154 mg/m(range 20 to 620 mg/m). Among the 77 patients, mean age was 38 years (range 24 to 54); 87% were Caucasian, 5% Hispanic, 4% Black, and 4% Asian/Other/Unknown; median CD4 count was 10 cells/mm; ACTG staging criteria were 78% poor risk for tumor burden, 96% poor risk for immune system, and 58% poor risk for systemic illness at baseline; and mean Karnofsky status score was 74%. All patients had cutaneous or subcutaneous lesions, 40% also had oral lesions, 26% pulmonary lesions, and 14% had lesions of the stomach/intestine.
Doxorubicin hydrochloride liposome injection was studied in an open-label, single-arm, multicenter study at a dose of 20 mg/mevery 3 weeks, until disease progression or unacceptable toxicity (Trial 5). Data is described for a cohort of 77 patients retrospectively identified as having disease progression on prior systemic combination chemotherapy (at least two cycles of a regimen containing at least two of three treatments: bleomycin, vincristine or vinblastine, or doxorubicin) or as being intolerant to such therapy. Forty-nine of the 77 (64%) patients had received prior doxorubicin HCl.
In Trial 4, a randomized, multicenter, open-label, trial in 474 patients with epithelial ovarian cancer after platinum-based chemotherapy, patients were randomized to receive either doxorubicin hydrochloride liposome injection 50 mg/mevery 4 weeks (n=239) or topotecan 1.5 mg/mdaily for 5 consecutive days every 3 weeks (n=235). Patients were stratified according to platinum sensitivity (response to initial platinum-based therapy and a progression-free interval of greater than 6 months off treatment) and the presence of bulky disease (tumor mass greater than 5 cm in size). The primary outcome measure was time to progression (TTP). Other endpoints included overall survival and objective response rate.
Doxorubicin hydrochloride liposome injection was studied in three open-label, single-arm, clinical studies of 176 patients with metastatic ovarian cancer (Trials 1, 2, and 3). One hundred forty-five of these patients were refractory to both paclitaxel-and platinum-based chemotherapy regimens, defined as disease progression while on treatment or relapse within 6 months of completing treatment. Patients received doxorubicin hydrochloride liposome injection at 50 mg/mevery 3 or 4 weeks for 3 to 6+ cycles in the absence of dose-limiting toxicity or disease progression.