Doxorubicin and docetaxel (Taxotere) are two of the most effective
drugs in metastatic breast cancer when used in monotherapy. The
objective of this study was to investigate the toxicity and efficacy
of the use of both drugs in full doses and sequentially in patients
with metastatic breast cancer with no previous chemotherapy.
The study included patients with histologically proven metastatic
breast cancer between the ages of 18 and 65 years, with no previous
chemotherapy for metastatic disease and an Eastern Cooperative
Oncology Group (ECOG) performance status < 2. Patients were
required to be 12 months from the end of adjuvant chemotherapy, and
to have adequate medullar, renal, and hepatic function, and
bidimensional measurable disease.
Thirty-one patients completed treatment between August 1, 1997, and
October 30, 1998. Their median age was 49 years (range: 3265
years). Previous adjuvant treatment for 20 patients included the
following: 15 patients, CMF (cyclophosphamide [Cytoxan,
Neosar]/methotrexate/fluorouracil); 3 patients, FEC
(fluorouracil/epirubicin [Ellence]/cyclophosphamide); 2 patients, FAC (fluorouracil/doxorubicin/cyclophosphamide).
The general ECOG status was as follows: 0, 19 patients; 1, 8
patients; 2, 4 patients. The median number of metastatic locations
was 2 (range: 15). The distribution of metastatic sites was
bone, 14 patients; nodes, 15 patients; liver, 11 patients; lung, 13
patients; soft parts, 10 patients; and other locations, 6 patients.
Patients were treated with doxorubicin 75 mg/m² IV, days 1, 14,
and 28, with granulocyte colony-stimulating factor (G-CSF, filgrastim
[Neupogen]), days 26, 1519, and 2933, followed by
docetaxel 100 mg/m² with standard premedication
schedule, days 42, 63, and 84. After the first 20 patients,
doxorubicin was administered every 21 days without G-CSF support. The
median relative dose intensity (RDI) of doxorubicin was 100% (range:
87%100%), and the RDI of docetaxel was 87% (range: 33%100%).
Toxicity was manageable and most of the patients were within grade
1/2 toxicity. Eight patients (25%) had febrile neutropenia after
doxorubicin administration and 8 after docetaxel administration.
Seven of those occurred after the first cycle of docetaxel when the
accelerated schedule of doxorubicin was used. None of the patients
experienced clinical cardiotoxicity.
There were 7 complete responses (23%), 14 partial responses (45%), 6
disease stabilizations, and 4 progressions. The overall response rate
was 68% (95% CI: 52%84%). The median time to progression was 9
months, with 19 patients (range: 115+ months) without
documented disease progression.
CONCLUSION: Sequential administration of doxorubicin and docetaxel is
highly effective in first-line treatment of metastatic breast cancer
with a manageable toxicity, which is mainly febrile neutropenia. The
frequency of this adverse effect can be reduced by using doxorubicin
every 21 days.