Abstract

THERAPEUTIC APPLICATION OF ADRIAMYCIN, XELODA AND CYTOXAN IN BREAST CANCER

Parvathi M. L.*

ABSTRACT

Adriamycin (Doxorubicin) is the most active single agent in the treatment of metastatic breast cancer. The response rate of Adriamycin in breast cancer is definitely related to the extent of prior treatment. Adriamycin is active against breast cancer over a wide range of dose levels and the response rate is quite similar at dose levels ranging from 40-75 mg/m2. The toxicity associated with Adriamycin therapy in- cludes nausea and vomiting in approximately 2/3 of the patients and alopecia in nearly all patients. ekly schedule of Adriamycin is yet to be determined, it is reasonable to assume that the smaller dose levels would result in lower peak plasma levels of Adriamycin, thus exposing the myocardium to lower concentrations of Adriamycin. ekly schedule of Adriamycin is yet to be determined, it is reasonable to assume that
the smaller dose levels would result in lower peak plasma levels of Adriamycin, thus exposing the myocardium to lower concentrations of Adriamycin. They report here the results of a phase II study of Adriamycin administered as a continuous in- fusion in patients with metastatic breast cancer previ- ously treated with chemotherapy other than Adria- mycin. This study was carried out among 27 patients with metastatic breast cancer previously treated with cyclo- phosphamide, methotrexate and 5-fluorouracil (CMF). In addition to the CMF chemotherapy 12 patients had received vincristine and prednisone (Cooper's regimen); fourteen patients had received endocrine therapy either with tamoxifen or oophorectomy, depending on their age and menstrual status. Because of the known risk of tissue necrosis and ul- ceration associated with extravasation of Adriamycin, a central venous catheter was inserted for administra- tion of continuous infusion of Adriamycin. The dose of Adriamycin was kept constant at 60 mg/ m2 per course and the treatment was repeated at three- week intervals or longer depending on recovery from myelosuppression. The acute toxicity associated with each course of treatment was carefully recorded. One patient could not be evaluated for response be- cause she received only one course of Adriamycin in- fusion and refused further treatment. Of the remaining 26 patients, one achieved a complete response, and 12 patients achieved partial response for an overall objective response rate of 50% (95% confidence limits, 30%- 70%). Six patients improved, four of them had minor objective regression, and two showed no objective change in their tumor. In seven patients the disease progressed after two to three courses of adriamycin treatment. The acute gastrointestinal effects of Adriamycin were markedly reduced when the drug was used as a contin- uous infusion. Twelve patients had no nausea or vom- iting, 11 patients had mild nausea or occasional vom- iting and only four patients (15%) had significant nausea and vomiting. The nausea and vomiting were generally observed at the end of the first day of infusion and appeared to be more marked with 24- and 48-hour infusions and were rarely observed during the 96-hour infusions. Four patients had a mild degree of stomatitis, which occurred approximately 10 days following treat- ment. Myelosuppressive toxicity of Adriamycin infusion appeared to be similar to that observed with the stan-dard schedule of Adriamycin administration.

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