ASCO--Doxorubicin (Adriamy-cin) plus paclitaxel(Drug information on paclitaxel) (Taxol) used in combination resulted in better overall response rates and longer time-to-treatment failure than either agent used alone as first-line treatment of metastatic breast cancer, George W. Sledge, Jr., MD, of Indiana University School of Medicine, reported at the ASCO meeting.
This randomized phase III intergroup trial, the first to compare doxorubicin(Drug information on doxorubicin) and paclitaxel in this setting, included 683 eligible patients with stage IV metastatic breast cancer. "This study is important because it places a new drug, Taxol, in context," Dr. Sledge said. "It tells us that this drug is fully the equivalent of the best current drug [doxorubicin] for treating advanced breast cancer."
Doxorubicin (60 mg/m² every 3 weeks) and paclitaxel (175 mg/m²/24 hr every 3 weeks) given alone produced equivalent response rates (36% for doxorubicin; 34% for paclitaxel).
The response rate for the combination (doxorubicin, 50 mg/m², followed 4 hours later by paclitaxel, 150 mg/m²/24 hr, plus G-CSF) was significantly better at 47%. In the combination, doxorubicin was given for a maximum of eight cycles, whereas paclitaxel could be continued until time of progression.
Median time-to-treatment failure was equal for the single-agent regimens (5.9 months for doxorubicin; 6 months for paclitaxel), but significantly higher (8 months) for the combination.
The three arms were equal, however, in median overall survival (18.9, 22.2, and 22 months, respectively, for doxorubicin, paclitaxel, and the combination), and in quality of life measurements. "The more intensive therapy, in this case the drug combination, did not improve quality or length of life," Dr. Sledge said.
He pointed out that since patients on the single-agent arms were allowed to cross over to the other single-agent arm at the time of progression, the comparison is, in effect, between the combination therapy and sequential single-agent therapy. Objective responses were similar whether patients crossed over from doxorubicin to paclitaxel (22%) or from paclitaxel to doxorubicin (20%).
Severe toxicity (grade 4/5) was more common in the paclitaxel-alone group (169 patients versus 109 patients on doxorubicin and 135 patients on doxorubicin plus paclitaxel). No greater cardiotox-icity was seen with the combination than with doxorubicin alone.
"Doxorubicin is no longer the single most effective agent in metastatic breast cancer," Gabriel N. Hortobagyi, MD, of M.D. Anderson, said in his commentary at the plenary session presentation. "Furthermore," he added, "this trial established for the first time that patients whose disease is refractory to a taxane still have sensitivity to doxorubicin."
Dr. Hortobagyi called the combination regimen "a reasonable choice for treating metastatic breast cancer," and he acknowledged Dr. Sledge and his colleagues for "providing one more important step in the systematic process of incorporating a new agent into the management of breast cancer."