Abstracts #317 and #322 attest to the high degree of antitumor activity of docetaxel(Drug information on docetaxel) (Taxotere) in the management of locally advanced breast cancer. In abstract #317 the authors tested two hypotheses: first, that the administration of a noncross-resistant cytotoxic regimen after induction or neoadjuvant chemotherapy improved the outcome of combined-modality treatment for both responders and nonresponders to neoadjuvant chemotherapy; and second, that the addition of docetaxel to a standard, anthracycline-containing regimen improved both clinical and pathologic response rates in locally advanced breast cancer.
The first hypothesis was previously tested by the Cancer and Leukemia Group B (CALGB) and the M. D. Anderson Cancer Center in three separate protocols, which first demonstrated the validity of the hypothesis. However, the antitumor potency of docetaxel, even in the anthracycline-resistant subset of breast cancers, made this confirmatory trial quite compelling. With these results in the locally advanced setting, and similar results obtained by adding paclitaxel(Drug information on paclitaxel) (Taxol) to the AC (doxorubicin [Adriamycin]/cyclophosphamide [Cytoxan, Neosar]) regimen in the adjuvant treatment of primary operable breast cancer, the use of sequential, noncross-resistant cytotoxic regimens for optimal results has been clearly established. The magnitude of the benefit obtained by the addition of docetaxel was quite substantial, not only in the group responding to the anthracycline-containing regimen, but especially in the anthracycline-resistant population.
Mature results to determine the influence of docetaxel on time to progression and survival are awaited with interest. In the meantime, the dramatically higher response rate obtained in the preoperative setting indicates that this regimen will convert a higher proportion of inoperable breast cancers into operable ones, and fewer patients with large primary tumors will require a total mastectomy when treated with CVAP (cyclophosphamide/vincristine/doxorubicin/prednisolone) followed by docetaxel.
The German multicenter trial reported in abstract #322 was the second phase of the German clinical evaluation of the doxorubicin(Drug information on doxorubicin)/docetaxel combination. Their first exploratory study demonstrated that this combination was highly effective and well tolerated. Perhaps because the antitumor efficacy observed in their pilot study was so substantial (suggestive of superiority to other standard, anthracycline-containing regimens), the investigators refrained from comparing it formally to a doxorubicin/cyclophosphamide-type regimen. Instead, the randomization was to additional therapy with tamoxifen(Drug information on tamoxifen) (Nolvadex) for one of the groups. It is then no surprise that the outcome of treatment was virtually identical in the two arms.
Of note was the fact that almost 70% of these patients, all of who had tumors larger than 3 cm, were ultimately treated with breast-conserving surgery, while regimen-related toxicity was minimal to moderate. Somewhat disappointing in the German studies is the low pathologic complete remission rate, despite the addition of docetaxelarguably the most effective antitumor agent in existence today for breast cancerto the regimen. Nevertheless, this regimen can induce a rapid clinical response that leads to breast-conserving therapy for the majority of patients. Alternative strategies need be developed to improve the pathologic complete remission rate and its effect on prolongation of survival for these high-risk, large breast cancers.
Gabriel N. Hortobagyi, MD, FACP