Main clinical uses of liposomal doxorubicin

AUGUSTOVSKI, F; PICHON-RIVIERE A,; ALCARAZ A; BARDACH, ARIEL; COLANTONIO, LISANDRO; FERRANTE, D; GARCIA MARTÍ, SEBASTIAN; GLUJOVSKY, D; LOPEZ, A; REGUEIRO, A

Documentos de Evaluaciòn de Tecnologías Sanitarias

IECS

Año: 2006 p. 1 - 30

1668-2793

This report is intended to assess the available evidence on the usefulness of liposomal doxorubicin for most common clinical uses.I- Pegylated Liposomal Doxorubicin and Non-Pegylated Liposomal Doxorubicin for the Treatment of Metastatic Breast CancerTwo randomized clinical trials (RCTs) which included 224 and 509 treatment-naive metastatic breast cancer patients who were randomized to receive either pegylated liposomal doxorubicin or conventional doxorubicin, found that the response rate, time to disease progression and median survival were similar for both groups. Cardiotoxicity was most commonly observed in the conventional doxorubicin group (approximately 25 vs. 10%). Another RCT randomized 160 treatment-naive metastatic breast cancer patients to receive cyclophosphamide in combination with non-pegylated liposomal doxorubicin or epirubicin (another anthracycline). The rate of total response and median survival was similar for both groups. Median time to disease progression was shorter for the liposomal group (5.6 versus 7.7 months; p=0.02). Cardiotoxicity was similar and low in both groups (11.84% and 10.26%). One RCT randomized 301 metastatic breast cancer patients who had failed a first or second line regimen with taxanes to receive pegylated liposomal doxorubicin or two control groups: vinorelbine or mytomicine C with vinblastine. Survival rate and progression-free survival was similar in the liposomal doxorubicin and the control groups when jointly analyzed.II- Pegylated Liposomal Doxorubicin for the Treatment of Multiple MyelomaTwo RCTs which randomized 259 and 192 patients to receive vincristine + dexamethasone + conventional (VAD) or liposomal (VADlip) doxorubicin were found. The rate of objective response, disease-free survival and overall survival were similar for both groups. Alopecia was most frequent in the VAD group and Hand-Food erythrodysesthesia, in the VADlip group.III- Pegylated Liposomal Doxorubicin for the Treatment HIV (Human Immunodeficiency Virus) Related to Kaposi SarcomaOnly two clinical trials which compared liposomal doxorubicin with standard treatments and one Cochrane revision of both were found. They included 499 patients with mucocutaneous or extensive visceral involvement and a CD4 count lower than 200 who were assigned to liposomal doxorubicin or bleomicine and vincristine (plus conventional doxorubicin in one of the studies). There were no significant differences in death risk among the different treatments. The response for the liposomal group was higher than the control, RR 2.16; (95% CI: 1.68 to 2.78). There were fewer treatment discontinuations in the liposomal group, RR 0.57; (95% CI: 0.48 to 0.68), but more cases of opportunistic infections, RR 1.42; (95% CI: 1.12 to 1.80).IV- Pegylated Liposomal Doxorubicin for the treatment of Advance Ovarian Cancer (New Indication)Its use was assessed as second line treatment in three RCTs which compared this drug against topotecan and paclitaxel. The RCT that evaluated the use of liposomal doxorubicin vs. topotecan and the one that evaluated it against paclitaxel reported that disease-free survival rates, total response rate and survival were similar for both groups.Another RCT compared the use of paclitaxel versus liposomal doxorubicin in combination with cyclophosphamide and cisplatin: a better survival rate was found in the combination group.NICE (National Institute of Clinical Excellence) of United Kingdom, recommends liposomal doxorubicin as an option in second line treatments (or after) for those women with advanced ovarian cancer partially sensitive, resistant or refractory to platinum, or for those who are allergic to platinum-based agents.Considering as an example the indication of breast cancer treatment in a woman whose body surface area is 1.7m2, the retail price of each conventional doxorubicin cycle is between $400 and $1,000, and the cost of liposomal doxorubicin is between $5,700 and $14,000, depending on the dose and trademark used (Argentine pesos, 2006). This cost does not include the other related medications used in the appropriate cases.