Randomized phase II trial of carminomycin versus 4'-epidoxorubicin in advanced breast cancer.

Abstract

Sixty-three evaluable patients with advanced breast cancer were randomly allocated to receive three-week intravenous courses of carminomycin (18 mg/m2) or 4'-epidoxorubicin (90 mg/m2). The former yielded one (3%) partial response for nine weeks among 29 patients whereas, in the other arm, nine (27%) of 34 patients achieved partial response for a median of 28 weeks (range, nine to 36 weeks; p less than 0.02). The major toxic effect of these anthracyclines was leukopenia with median white blood cell nadirs of 1,600/microL (range, 300-4,000/microL) versus 1,800/microL (range, 500-4,300/microL), respectively. Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia. Patients whose disease failed to respond to first-line anthracycline received doxorubicin (60 mg/m2) every three weeks. Four partial responses were obtained among 19 patients previously treated with carminomycin. Following 4'-epidoxorubicin therapy, one of 12 evaluable patients also attained partial response. Survival curves were not affected by the initial treatment option. Carminomycin has marginal activity against breast cancer whereas 4'-epidoxorubicin deserves further evaluation of its therapeutic index relative to doxorubicin. The design used in this trial appears attractive for prompt phase II evaluation of anthracycline analogs.

Current Status of Epirubicin (Farmorubicin) in the Treatment of Solid Tumours

“…Seven early phase I1 trials all used the 3-weekly schedule (154,(219)(220)(221)(222)(223)(224). The average response rate in 147 patients is 25%, but these trials were all very small, recruiting from 13-36 patients with response rates ranging from 6% to 43%.…”

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

“…Subsequently clear evidence emerged that not all anthracyclines had equal efficacy in metastatic breast cancer. For example idarubicin, esorubicin and carcinomycin had inferior response rates to doxorubicin and/or epirubicin (Rozencweig et al, 1984;Bonfante et al, 1986;Lopez et al, 1989). However, in vitro studies indicate that daunorubicin has equivalent cytotoxicity to doxorubicin in breast adenocarcinoma lines (Wiles et al, 1997).…”

Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer

“…At the time this study started, clinical experience suggested that doxorubicin 75 mg m-2 and epirubicin 90 mg m-would induce similar degrees of myelotoxicity (Rozencweig et al, 1984;Bonfante et al, 1982). In 1990, Mouridsen reviewed 10 years of clinical experience with epirubicin and calculated the equitoxic dose ratio for the haematological toxicity of doxorubicin and epirubicin to be 1:1.2 (Mouridsen et al, 1990).…”

“…similar anti-tumour activity but less toxicity (Casazza et al, 1980;Schrauer et al, 1981;Bonfante et al, 1982;Young and Weenen, 1984). In the early phase II studies in metastatic breast cancer, epirubicin showed anti-tumour activity similar to that of doxorubicin (Rozencweig et al, 1984). The toxicities encountered with epirubicin therapy were: leucopenia, nausea and vomiting and no severe life-threatening cardiac toxicity up to a cumulative dose of about 1000 mg m-2.…”

“…bolus injection every 3 weeks. Based on the limited data, available at that time, of previous investigations, epirubicin 90 mg m-2 was anticipated to induce degrees of myelosuppression equivalent to doxorubicin 75 mg m-2 (Rozencweig et al, 1984;Bonfante et al, 1982). Haematological growth factors were not used in this study.…”