STUTTGART, GermanyMitoxantrone (Novantrone) alone gives
high-risk metastatic breast cancer patients a better quality of life
than a combination of fluorouracil, epirubicin, and 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
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 every 3 weeks. The
other group received 500 mg/m² of fluorouracil, 50 mg/m² of
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,
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.
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 (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.