A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma.

Abstract

Three hundred thirty-one women with metastatic breast cancer were randomized to receive combination chemotherapy with either cyclophosphamide, Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ), and fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and fluorouracil (CAF). Patients could not have had prior chemotherapy, although adjuvant chemotherapy was acceptable. Initial doses were 500 mg/m2 of cyclophosphamide and 500 mg/m2 of fluorouracil with either 10 mg/m2 of mitoxantrone or 50 mg/m2 of doxorubicin, administered intravenously (IV) on day 1 and repeated every 3 weeks. There were no statistically significant differences in pretreatment or prior therapy characteristics between the groups. For patients assigned to the CNF and CAF groups, respectively, 25 (18%) were premenopausal, 39 (40%) were estrogen receptor (ER) negative, 39 (38%) had a disease-free interval less than 1 year, and 24 (26%) had received prior adjuvant chemotherapy. All patients were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. None of these parameters were statistically significant favoring one regimen over the other. The response rate (complete [CR] and partial response [PR]) was 29% for the CNF group (95% confidence interval of 22% to 37%) and 37% for the CAF group (95% confidence interval of 29% to 45%). The median response duration and TTF were 171 days and 125 days for the CNF group and 254 days and 147 days for the CAF group, respectively. The median survival times for the CNF group and the CAF group were 377 and 385 days, respectively. The major dose-limiting toxicity for both regimens was leukopenia, manifested as granulocytopenia. The incidence of stomatitis/mucositis was 10% in the CNF group and 19% in the CAF group. Alopecia occurred in 49% of CNF patients (severely for 4%) and in 86% of CAF patients (severely for 39%). Nausea/vomiting occurred in 80% of CNF patients and in 81% of CAF patients; the degree of severity was also comparable. There was significantly less cardiotoxicity observed in the CNF group compared with the CAF group. Although CNF is somewhat less effective in overall response rate, survival curves are identical. CNF can be offered to patients who reject anthracycline-containing regimens because of fear of alopecia.

Discordance between physicians' estimations and breast cancer patients' self-assessment of side-effects of chemotherapy: an issue for quality of care

“…Concordance between patient's self-assessment and clinical reports is moderately correct (Kappa coefficient between 0.45 and Figure 1 Comparison of chemotherapy side-effects evaluated by patients with those reported by physicians in medical records (n = 30,180 cycles of chemotherapy), *, Patient; physician; (,Cohen's Kappa coefficient; *P < 0.05; **P<10-2; ***P < 10-3; NS, not significant 0.75; Landis and Koch, 1977) (Love et al, 1989;Portenoy et al, 1994a) that the number of disturbing physical symptoms experienced by cancer patients is strongly associated with their overall quality of life during chemotherapy treatment. Our study, carried out in a group of female patients with standard risk breast cancer, also found similar frequencies of symptoms, such as nausea and vomiting, associated with NCF chemotherapy as in other groups of patients (metastatic breast cancers) receiving the same regimen (Bennett et al, 1988). Detailed comparison of our findings with those of this previous study are difficult, and a more systematic investigation in our own sample may explain higher frequencies of declarations for symptoms such as hair loss (77% vs 49%) or sore mouth (30% vs 10%).…”

Concomitant chemoradiotherapy for patients with nonmetastatic breast carcinoma

“…Some difficulties arise for these comparisons, because investigators usually evaluated toxicity of chemotherapy at base of mitoxantrone using the World Health Organization (WHO) criteria 9 or self-administered instruments that are not as detailed as our chemotherapy side-effect questionnaire. 10,11 Except for the study by Sprangers et al, 12 similar problems exist with the assessment of radiotherapy side effects. [13][14][15] Contrary to The Breast Cancer Chemotherapy Questionnaire (BCQ) 16 and the Functional Assessment of Cancer Therapy-Breast (FACT-B), 17 also devised specifically for breast carcinoma patients, the EORTC QLQ-BR, 23 tested in the study by Sprangers et al 12 includes side effects related to both chemotherapy and radiotherapy.…”

Phase I/II study of gemcitabine plus mitoxantrone as salvage chemotherapy in metastatic breast cancer

“…A number of studies have demonstrated that this drug has an activity comparable to anthracyclines, but it is much less toxic (Bennett et al, 1988;Henderson et al, 1989). Given as a single agent, mitoxantrone is able to achieve up to 27% response in patients previously treated with chemotherapy (Brufman et al, 1993).…”