A randomized trial comparing mitoxantrone with doxorubicin in patients with stage IV breast cancer

Abstract

Mitoxantrone (Novantrone; dihydroxyanthracenedione) is an anthraquinone previously shown to be active in human breast cancer. It appears to have less toxicity than doxorubicin. Results of this phase II-III randomized cross-over trial to determine the relative efficacy and toxicity of mitoxantrone in comparison to doxorubicin, are presented. Patients with measurable, recurrent breast cancer with limited prior chemotherapy with or without radiotherapy for metastatic disease, and who had not been exposed to prior doxorubicin, were randomized to receive either mitoxantrone or doxorubicin every three weeks with cross-over on progression. Response rates, duration of remission, time to treatment failure, and drug toxicity, including cardiac toxicity evaluated with serial radionuclide angiocardiography, were evaluated. Differences in the response rates for the two groups were not statistically significant. Neither time to treatment failure nor duration of response are significantly different (p greater than 0.05). With respect to toxicity, mitoxantrone treated patients consistently exhibited a lower incidence and less severe drug toxicity as compared to their doxorubicin-treated counterparts. Cardiac toxicity was carefully monitored and thus four patients on doxorubicin have had drug related congestive heart failure, as compared to none on mitoxantrone. In summary, mitoxantrone appears to be as active as doxorubicin in patients with stage IV breast cancer previously treated with chemotherapy; however, mitoxantrone causes significantly less nausea, vomiting, stomatitis and alopecia at doses which induce equal or greater myelosuppression than doxorubicin, and appears to be less cardiotoxic.

Androgen receptors as a prognostic and predictive factor in breast cancer.

“…In 1984 Bryan observed in a group of 1371 breast cancer patients that AR (+) had better response to treatment and higher 5-year survival than AR (-) ones [14]. On the other hand, Allegra stated that AR expression in patients with advanced tumors was not associated with better response to hormone therapy [15]. Thus the expression of AR and ER on cancer cells may have additional therapeutic consequences, particularly for tumors showing high proliferative activity and AR expression as the sole steroid receptor.…”

Phase II Study of Pirarubicin in Metastatic Breast Cancer

“…In recent studies comparing doxorubicin with mitoxantrone, similar results were achieved. The response rate in non-pretreated patients [2] with doxorubicin was 35%, and 25% with mitoxantrone. The remission lasted 7.7 months (doxorubi cin) and 5.1 months (mitoxantrone).…”

Cisplatin, Methotrexate and Mitoxantrone in Patients with Metastatic or Advanced Urothelial Cancer

“…The cisplatin dose was almost doubled in the present trial compared with M-VAC (33.3 vs. 17.5 mg /m 2 /week). In randomized studies where doxorubicin is compared with mitoxantrone (15,16), the mitoxantrone dose is approximately 20% of the doxorubicin dose, whereas in this study the mitoxantrone dose was 44% of the doxorubicin dose in M-VAC. In a trial where patients with breast cancer were treated with 10 mg/m 2 mitoxantrone and 100 mg/m Abbreviations: Cyst = cystectomy; Ln = lymph node(s); PS =performance status; Retroper = retroperitoneal.…”