Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer

Abstract

Myocet appears to be an acceptable alternative to epirubicin as a first-line treatment for patients with metastatic breast cancer because it combines the dose-effect reliability of doxorubicin with the level of safety provided by epirubicin.

Non-pegylated liposome-encapsulated doxorubicin citrate plus cyclophosphamide or vinorelbine in metastatic breast cancer not previously treated with chemotherapy: A multicenter phase III study

“…In fact, in this study which enrolled 296 patients, an objective response of 43% was observed in both arms, with a significant reduction of cardiotoxicity (6 vs. 21%; P= 0.0002) in favor of MC patients (20). A further phase III study (19) randomized 160 patients to receive cyclophosphamide 600 mg/m 2 plus either epirubicin 75 mg/m 2 or liposomal doxorubicin 75 mg/m 2 . No significant differences were observed in the rate of asymptomatic reduction in LVEF (11 vs. 10%).…”

“…Pharmacokinetic studies have demonstrated that doxorubicin in Myocet is bioavailable, metabolized and excreted in a manner similar to that of conventional doxorubicin, but in a slower rate sparing myocardial cells. Moreover, a number of clinical studies (18)(19)(20) have demonstrated comparable activity and lesser toxicity of Myocet vs. conventional doxorubicin. In addition, data from a phase III randomized controlled clinical trial, comparing Myocet plus cyclophosphamide (MC) vs. adriamycin plus cyclophosphamide (AC) in advanced breast cancer, demonstrated that Myocet significantly reduced the cumulative cardiac toxicity, while providing comparable antitumor efficacy.…”

“…Therefore, liposome encapsulated doxorubicin does not easily reach heart tissue and a higher cumulative dose of liposome-encapsulated doxorubicin can be delivered to the patient (16,17). Results from phase III trials demonstrated that liposome-encapsulated doxorubicin and doxorubicin are equivalent in terms of antitumor efficacy (18)(19)(20). In particular, Myocet in combination with cyclophosphamide showed an efficacy equivalent to doxorubicin, with a better profile in terms of cardiotoxicity and hematological toxicity (20).…”

New approaches in the management of advanced breast cancer – role of combination treatment with liposomal doxorubicin

“…42 There was no significant difference in the primary endpoint of ORR (46% vs 39%) although TTP was longer for LED (7.7 vs 5.6 months; P = 0.022). There was no significant difference in the incidence of cardiotoxicity (12% vs 10%).…”

“…41,42,76,77 However, the combination of LED with other cytotoxic agents has been less intensively studied than is the case for PLD. The early phase nature of these trials and the small numbers of patients treated should again be emphasized (Table 3).…”