Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer.

Abstract

Three hundred twenty-five women with metastatic adenocarcinoma of the breast who had failed one prior chemotherapeutic regimen for advanced disease were randomized to receive 14 mg/m2 of mitoxantrone or 75 mg/m2 of doxorubicin intravenously (IV) every 3 weeks. Enrollment was closed on October 31, 1984, after 165 patients were randomized to mitoxantrone and 160 patients to doxorubicin. Patients randomized to the two treatment groups were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. The response rate to mitoxantrone was 20.6%, to doxorubicin 29.3% (P = .07). The median response duration was 151 days for the mitoxantrone group and 126 days for the doxorubicin group (P = .16). The median TTF was 70 days in the mitoxantrone group and 104 days in the doxorubicin group (P = .36). The median survival of patients initially randomized to receive mitoxantrone was 273 days; for doxorubicin 268 days (P = .40). There were three responses among 77 patients crossed over to mitoxantrone after initial treatment with doxorubicin. The major dose-limiting toxicity for both drugs was leukopenia. There was significantly less severe and less frequent toxicity with mitoxantrone administration. Severe nausea and vomiting occurred in 9.5% of mitoxantrone patients and 25.3% of doxorubicin patients (P less than .001). The incidence of severe stomatitis and mucositis was 0.6% in the mitoxantrone group and 8.4% in the doxorubicin group (P = .001). Severe alopecia occurred in 5.1% of mitoxantrone patients and 61.0% of doxorubicin patients (P less than .001). A life-table comparison of the cumulative dose to the development of a cardiac event showed that mitoxantrone had significantly less cardiotoxicity than doxorubicin (P = .0005). This study demonstrates that mitoxantrone is active as a single agent in the treatment of metastatic breast cancer. Compared with doxorubicin it appears to be marginally less active and significantly less toxic. We conclude that mitoxantrone can be used alone or with other standard drugs to palliate the symptoms of metastatic breast cancer, especially in settings where drug toxicity is an important consideration.

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

“…Combining the results of this study with the two published reports DaunoXome has shown objective responses in eight out of 35 (23%) evaluable patients (Anonymous, 1996;Darskaia et al, 1999). The response rate for this relatively non-toxic anthracycline based therapy must be taken in context with those reported for single-agent doxorubicin which vary from 30 -34% in recent randomised phase III studies (Henderson et al, 1989;Sledge et al, 1997;Chan et al, 1999;Norris et al, 2000). The overall time to tumour progression of 5 months (8.5 months in those patients treated at 120 and 150 mg m 2 ) and median survival of 13.75 months are in keeping with the results reported for large randomised studies of doxorubicin when used alone or as part of a combination regimen in the treatment of symptomatic relapsed breast cancer (Norris et al, 2000).…”

High-dose chemotherapy (CTM) for breast cancer

“…22 A lifetime cumulative doxorubicin equivalent dose (⌺ Doxo Eq) was calculated for each patient [⌺ Doxo Eq = ⌺ doxorubicin (in mg/m 2 ) + (⌺ mitoxantrone (in mg/m 2 )) × (2.6)]. 23 …”

Docetaxel: Overview of an Active Drug for Breast Cancer

“…When given as a 24-hour infusion, paclitaxel was roughly equivalent in performance to the smaller doxorubicin dose of 60 mg/m 2 [4]. In the final study, doxorubicin was somewhat superior to mitoxantrone [5].…”

“…This phenomenon may account both for the fact that paclitaxel appears to be more active when given as a 24-hour rather than a 3-hour infusion, and that docetaxel given over 1 hour seems clinically to be at least as active as paclitaxel infused over 24 hours [2][3][4][5]15].…”