STUTTGART, GermanyMitoxantrone (Novantrone) alone gives high-risk metastatic breast cancer patients a better quality of life than a combination of fluorouracil(Drug information on fluorouracil), epirubicin, and cyclophosphamide(Drug information on cyclophosphamide) (FEC), according to results presented at the 36th Annual Meeting of the American Society of Clinical Oncology. Yet the single agent appears to work as well as combination therapy when compared for several endpoints.
There is agreement that in metastatic breast cancer, palliation has to be weighed against survival and toxicity, Else G. Heidemann, MD, PhD, head of the Medical Department, Deaconess Hospital, Stuttgart, Germany, said to explain the rationale for the study. Therefore, the dogma that patients fulfilling high-risk criteria have to be treated with high-dose chemotherapy upfront had to be challenged. Time to progression and overall survival are more important than remission rate.
Dr. Heidemann and her collaborators in the Interdisciplinary Breast Cancer Working Group of the German Cancer Society randomized 260 high-risk breast cancer patients into two groups.
One group received 12 mg/m² of mitoxantrone(Drug information on mitoxantrone) every 3 weeks. The other group received 500 mg/m² of fluorouracil, 50 mg/m² of epirubicin(Drug information on epirubicin), and 500 mg/m² of cyclophosphamide every 3 weeks. Treatment continued either until complete remission plus two cycles or until progressive disease, for a maximum of 12 cycles of treatment. Second-line treatment consisted of vindesine, mitomycin, and prednisolone(Drug information on prednisolone).
The researchers found no significant differences between monotherapy and combination therapy in various measures of efficacy. For example, the time to progression in the mitoxantrone group was 3.83 months vs 4.08 months in the combination group, a nonsignificant difference.
The median overall survival was 428 days in the mitoxantrone group vs 481 days in the combination group, again statistically nonsignificant.
In contrast, the researchers did find a significant difference in quality of life between the two treatment arms.
To estimate quality of life, they used a modified Brunners score that incorporated time to progression; performance status (determined before each treatment cycle, averaged, and compared with performance status before the start of treatment); patient rating (the answer to the question Do you feel the treatment helps? scored as either positive or negative); and toxicity.
If the score was positive, we thought the patient had gained from treatment, Dr. Heidemann said. If the score was negative, we called it no gain from treatment.
The scores differed significantly between the treatment arms, with patients in the mitoxantrone group scoring +3.39 on the modified Brunners score vs -1.41 in the combination group.
The largest contributor to the difference between groups was toxicity. Alopecia and vomiting were much heavier in the combination group than in the single-agent treatment group, Dr. Heidemann said.
The study revealed several patient criteria that appeared relevant to overall survival, but did not find any particular benefit to any subgroup from being in one or the other treatment group.
The researchers currently are continuing the study with about 300 patients randomized to either mitoxantrone alone or mito-xantrone plus docetaxel(Drug information on docetaxel) (Taxotere) to determine whether certain subgroups might benefit from more aggressive treatment.
Dr. Heidemann said, There was no difference between single-agent mitoxantrone and combination chemotherapy in terms of objective remission rate, remission duration, time to response, time to best response, time to progression, or overall survival. However, she added, there was significantly less hair loss and vomiting in the single-agent patients, who as a result had a significantly better quality of life.