Weekly High-Dose Neoadjuvant Paclitaxel Appears Promising

 PROVIDENCE, RI—Weekly, high-dose neoadjuvant chemother-apy with paclitaxel (Taxol) resulted in an 87% clinical response rate in a small pilot study aimed at assessing the feasibility and tolerability of the regimen in patients with stage IIB-IIIB breast cancer.

Among 38 patients who received six weekly 175 mg/m² doses of paclitaxel (one or two 8-week cycles) before surgery, 11 had a complete remission and 22, a partial remission. Five additional patients had stable disease, and only one patient had progressive disease, William Sikov, MD, reported at the San Antonio Breast Cancer Symposium.

“The impressive thing about this particular regimen was the rapidity with which patients responded,” Dr. Sikov, of Brown University, said at a poster session. “A majority of the patients went to surgery after just one cycle of therapy. Many different types of neoadjuvant chemotherapy have produced fairly high response rates, but I think our response rate of 87% is on the high end, even among other very active regimens.”

Multiple factors contribute to the rationale for the weekly paclitaxel regimen, he said. Paclitaxel is one of the most active single agents in advanced breast cancer. In theory, weekly dosing should result in maintenance of tissue levels, afford more opportunity for dose escalation, and possibly lead to enhancement of paclitaxel’s apoptotic and antiangiogenic properties. Additionally, use of single-agent paclitaxel in the neoadjuvant setting saves the doxorubicin-cyclophosphamide combination for adjuvant use.

The trial included 39 patients, whose median age was 49 years. Ten of the patients were older than 60. The cohort included 14 patients with stage IIB disease, 7 with stage IIIA cancer, and 18 with stage IIIB disease, including 11 who had inflammatory breast cancer.

A single cycle of therapy was given to 24 patients, and the remaining 14 evaluable patients had two cycles of treatment. “We tried to give a second cycle of therapy to patients who had large tumors and those who had inflammatory breast cancer,” Dr. Sikov said. “We saw very clear evidence that some patients continued to respond into the second cycle.”

The median dose delivered was 131 mg/m²/wk. Dose modification was most often due to development of neutropenia, particularly during weeks 3 and 6. Overall, 86% of the patients developed grade 3-4 neutropenia. Five patients required dose modifications because of neurologic toxicity. Only one patient discontinued therapy because of toxicity.

Clinical Responses

Clinical responses included 3 complete responses (CRs) and 10 partial responses (PRs) in patients who had stage IIB cancer and 8 CRs and 12 PRs in patients with stages IIIA-B cancer. Among the stage IIIB patients with inflammatory breast cancer, there were 4 CRs and 4 PRs.

The paclitaxel regimen resulted in seven pathologic complete responses. Nine other patients had residual disease of 2 cm or less, 12 had residual disease of 2 to 5 cm, and seven had residual disease that exceeded 5 cm.

“The pathologic complete response rate was not quite what we had hoped for,” Dr. Sikov said, “but a 20% pathologic complete response rate is at least as good as is seen with other neo-adjuvant regimens.”