Abstract
The combination of mitozantrone, methotrexate and mitomycin (3M) gives a response rate of around 50% in patients with advanced breast cancer. The predominant toxicity is haematological. In this study, previously untreated patients were given 3M with increasing doses of mitozantrone (7-14 mg m-2) with recombinant human granulocyte colony-stimulating factor (metHuG-CSF) (filgrastim) to prevent marrow toxicity. Doses administered were 7 mg m-2 mitomycin i.v. 6 weekly, methotrexate i.v. 35 mg m-2 (maximum 50 mg) 3 weekly and mitozantrone i.v. 3 weekly as follows: 7 mg m-2, six patients (group 1); 10 mg m-2, six patients (group 2); 12 mg m-2, six patients (group 3); 14 mg m-2, six patients (group 4); all on day 1 for six cycles at the assigned dose. All patients received filgrastim (Amgen 0.3 mg ml-1) at a dose of 5 micrograms kg-1 subcutaneously daily on days 4-17 of each cycle. All treatment was given on an out-patient basis. A total of 24 patients were entered into the study. The median age was 63 years (range 48-75). ECOG performance status was 0 in ten, 1 in 11 patients and 2 in three patients. Locoregional disease alone was present in seven patients. The remainder had one or more sites of metastases. The actual dose administered to the 24 patients was as follows. The six patients in group 1 all completed six courses of treatment as per protocol. In group 2, three patients completed six courses, two stopped because of toxicity after one and four courses and one had progressive disease after one course. In group 3, three patients completed and three stopped early because of progressive disease. In group 4, two patients completed, one progressed after four courses and three responding patients stopped treatment because of toxicity. The maximum tolerated dose of mitozantrone in the 3M combination was 12 mg m-2. The use of filgrastim with increasing doses of chemotherapy prevents neutropenia, but other toxicities, namely thrombocytopenia and lethargy, then become dose limiting.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bronchud M. H., Howell A., Crowther D., Hopwood P., Souza L., Dexter T. M. The use of granulocyte colony-stimulating factor to increase the intensity of treatment with doxorubicin in patients with advanced breast and ovarian cancer. Br J Cancer. 1989 Jul;60(1):121–125. doi: 10.1038/bjc.1989.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crawford J., Ozer H., Stoller R., Johnson D., Lyman G., Tabbara I., Kris M., Grous J., Picozzi V., Rausch G. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med. 1991 Jul 18;325(3):164–170. doi: 10.1056/NEJM199107183250305. [DOI] [PubMed] [Google Scholar]
- Powles T. J., Jones A. L., Judson I. R., Hardy J. R., Ashley S. E. A randomised trial comparing combination chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincristine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer. Br J Cancer. 1991 Aug;64(2):406–410. doi: 10.1038/bjc.1991.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sheridan W. P., Begley C. G., Juttner C. A., Szer J., To L. B., Maher D., McGrath K. M., Morstyn G., Fox R. M. Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Lancet. 1992 Mar 14;339(8794):640–644. doi: 10.1016/0140-6736(92)90795-5. [DOI] [PubMed] [Google Scholar]
- Vincent M. D., Powles T. J., Coombes R. C., McElwain T. J. Late intensification with high-dose melphalan and autologous bone marrow support in breast cancer patients responding to conventional chemotherapy. Cancer Chemother Pharmacol. 1988;21(3):255–260. doi: 10.1007/BF00262781. [DOI] [PubMed] [Google Scholar]