Sequential Doxorubicin and Docetaxel in First-Line Chemotherapy for Metastatic Breast Cancer (GEICAM Study 9801)

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: 32–65 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: 1–5). 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 2–6, 15–19, and 29–33, 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: 1–15+ 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.

Click here for Dr. Gabriel N. Hortobagyi’s commentary on this abstract.