High‐dose mitoxantrone and cyclophosphamide without stem cell support in patients with high‐risk and advanced breast carcinoma

Abstract

BACKGROUND Currently employed high‐dose regimens for patients with breast carcinoma consist mainly of single‐cycle combinations of alkylating agents. In a previous Phase I trial, the authors developed a tandem high‐dose combination of two cycles of mitoxantrone and cyclophosphamide for the treatment of patients with metastatic breast carcinoma (MBC) and high‐risk breast carcinoma (HRBC). Treatment was delivered with granulocyte‐colony stimulating factor (G‐CSF) but without stem cell support to avoid potential tumor cell reinfusion. The objective was to validate the safety and obtain preliminary efficacy assessment of this combination in a Phase II trial. METHODS Fifty‐three patients were included: 27 patients with MBC and 26 patients with HRBC. After standard induction treatment, patients received two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 separated by a 4‐week interval. Patients received G‐CSF and ciprofloxacin until hematologic recovery. Follow‐up was performed in an outpatient setting. RESULTS One hundred one of 106 projected cycles (95%) were delivered. The mean dose intensities achieved were mitoxantrone 5.8 mg/m2 per week and cyclophosphamide 933 mg/m2 per week. Infection developed in 46% of the cycles, and platelet transfusions were required in 42%. Nonhematologic toxicity was mainly Grade 3 emesis. There were no toxic deaths. In 17 evaluable patients with MBC, 13 patients (77%) had response improvements, including 7 complete responses (41%). CONCLUSIONS Treatment with two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 with G‐CSF but without stem cell support was well tolerated. The dose intensities achieved approach those obtained with conventional high‐dose therapy. This combination warrants further investigation as an alternative to conventional high‐dose regimens. Cancer 2001;92:2508–16. © 2001 American Cancer Society.

Postoperative radiotherapy and mitoxantrone for anal sac adenocarcinoma in the dog: 15 cases (1991–2001)

“…Tolerability of MX in dogs is good with myelosuppression being the dose‐limiting toxicity (Ogilvie et al ., 1991b, 1994). In humans, the drug has activity against tumours of epithelial origin, including tumours of the breast, prostate, pancreas, salivary gland and ovary (Devita et al ., 2001; Perez‐Garcia et al ., 2001; Tournigand et al ., 2001; Levine et al ., 2002). A combined phase I/II veterinary trial indicated a 20% response rate in dogs with carcinomas (Ogilvie et al ., 1991a).…”