A dose-intensive outpatient regimen of doxorubicin and CMF (cyclophosphamide,
methotrexate, and fluorouracil) with growth factor support proved
to be effective and well tolerated in women with advanced breast
cancer, Mark L. Graham, MD, said at the San Antonio Breast Cancer
The regimen produced partial or complete responses in 20 of 34
women with stage II, III, or IV disease. The therapy caused some
problems with mucositis and cardiotoxicity, but was generally
well tolerated. However, the use of granulocyte colony-stimulating
factor (G-CSF, filgrastim; Neupogen) added $8,000 to $9,000 to
the cost of chemotherapy.
The regimen was evaluated by North Carolina investigators as a
means of dealing with patients who present with stage IIb (T3N0),
stage III, or stage IV breast cancer. The incidence of those stages
is twice the national average in North Carolina, said Dr. Graham,
a medical oncologist at the University of North Carolina School
of Medicine, Chapel Hill.
The patients were treated with neoadjuvant or adjuvant chemotherapy
regimens. The neoadjuvant regimen began with doxorubicin at a
dose of 75 to 90 mg/m²/d every 2.5 weeks for 10 weeks (four
cycles). Growth factor support began on day 4 and continued for
a minimum of 7 days at a dose of 4 to 6.2 mcg/kg/d. Chemotherapy
was followed by definitive surgery. After surgery, patients received
four cycles of CMF over 10 weeks. Growth factor support started
on day 3 and continued for a minimum of 7 days after the platelet
count exceeded 7,500.
Among patients who had definitive surgery first, acute adjuvant
doxorubicin began immediately after surgery. CMF then followed.
Eleven patients received doxorubicin as adjuvant therapy, and
23 received neoadjuvant therapy. The target dose was 36 mg/m²/wk,
which was achieved in 95% of the patients. All 34 patients finished
the four doxorubicin cycles, and 18 finished the cycles within
the 10-week schedule. Analysis of CMF dose objectives has not
been completed, Dr. Graham said.
Overall, 20 of 34 patients had clinical responses, including 9
partial responses and 11 clinical complete responses (see table).
Five patients had complete responses with respect to breast, lymph
nodes, and pathology. Of 23 patients who received neoadjuvant
doxorubicin, 9 were converted from mastectomy candidates to conservative
Patients required G-CSF support an average of 8.7 days per doxorubicin
cycle and 9 days per CMF cycle.
The doxorubicin regimen was associated with grade 3 mucositis
in 30% of patients. The toxicity typically occurred during the
last two cycles, Dr. Graham said. Grade 3 hand-foot syndrome occurred
in 20% of patients. Nausea and vomiting posed minor problems.
Growth factor support minimized neutropenia to 4 of 136 cycles
Doxorubicin was associated with a decrease in ejection fraction
from a mean of 65% to 56%. Some patients with lower ejection fractions
at baseline had losses of pumping activity in the low and below-normal
ranges, but only one patient had symptoms of heart failure, he
Toxicity data are incomplete for the CMF regimen. Anemia requiring
transfusion has occurred in about a quarter of 29 evaluable patients,
and 3 patients have developed thrombocytopenia.