Weekly Neoadjuvant Paclitaxel for Breast Cancer
Weekly Neoadjuvant Paclitaxel for Breast Cancer
Abstract & Commentary
By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC and is Editor of Clinical Oncology Alert. Dr. Ershler is on the speaker’s bureau for Amgen and does research for Ortho Biotech.
Synopsis: Paclitaxel, administered weekly, compared to once-every-3-weeks in a trial of primary systemic (neoadjuvant) treatment for operable breast cancer was shown by Green and colleagues at M.D. Anderson and Brown University to provide comparable clinical responses but superior rates of pathological complete response (pCR) and breast conservation. Both the weekly and q3 week regimens were followed by 4 cycles of fluorouracil/doxorubicin/cyclophosphamide (FAC).
Source: Green MC, et al. Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol. 2005;23:5983-5992.
The current study was designed to compare the anti-tumor efficacy of weekly vs once-every-3-week dosing of paclitaxel in the primary systemic treatment (PST) of patients with invasive breast cancer before surgery. For this, patients seen at either the University of Texas M.D. Anderson Cancer Center (Houston, TX), or at the Brown University Oncology Group (Providence, RI) with stage I-IIIA breast cancer were randomly assigned to receive neoadjuvant paclitaxel in doses administered either weekly (for a total of 12 doses of paclitaxel) or once every 3 weeks (4 cycles), followed by 4 cycles of fluorouracil/doxorubicin/cyclophosphamide (FAC) in standard doses administered every 3 weeks. Two different doses of paclitaxel were used based upon lymph node status defined by ultrasound and fine needle aspiration. Outcome measures included clinical response and extent of disease in the breast and lymph nodes after completion of all chemotherapy.
A total of 258 patients were enrolled at the 2 participating centers. Of these, 110 patients had histological evidence of lymph node involvement and 148 did not. Weekly paclitaxel followed by FAC was administered to 127 patients and once-every-3-weeks paclitaxel followed by FAC was administered to 131 patients. Clinical response to treatment was similar between groups. Patients receiving weekly paclitaxel had a higher pathologic complete remission (pCR) rate (28.2%) than patients treated with once-every-3-weeks paclitaxel (15.7%; P = 0.02) and the weekly treatment group also had a higher breast conservation rate (P = 0.05).
Commentary
The use of weekly chemotherapy, notably with taxanes has become a fairly popular approach, primarily for patients with metastatic breast cancer. Its popularity, although balanced by the necessity for increased office visits, is based upon demonstrated equivalent efficacy achieved with less toxicity.1 The current research, reported initially at ASCO in 2001, is finally in manuscript form and any delays in publication may be attributable to the analysis required for a fairly complex clinical trial design. For those women who were found to be node positive (by ultrasound and fine needle aspirate) and randomized to weekly therapy, a more intensive than usual dosing schedule was initially employed. The initial cohort (n = 13) received 175 mg/m2 by 3 hour infusion every week for 6 weeks followed by a 2-week break. This schedule resulted in a high percentage of grade 3 neurotoxicity (76.9%). The next cohort (n = 14) received paclitaxel at 150 mg/m2 by the same schedule. In this group, 50% developed grade 3 neurotoxicity, but neutropenia occurred commonly, necessitating treatment delays. Accordingly, all subsequent node positive subjects (n = 29) were treated with the same relatively high dose for weekly therapy (150 mg/m2) over a period of 3 hours for 3 weeks straight, followed by a 1-week break. This three week course comprised one cycle, and 4 cycles were completed before switching to FAC. Node negative patients randomized to weekly paclitaxel received 80 mg/m2 administered over 1 hour every week for 12 weeks. All patients (node positive and node negative) randomized to the once-every-3-week dosing received paclitaxel 225 mg/m2 administered as a continuous infusion over a period of 24 hours on day 1 of each of 4 cycles. All patients (weekly or once-every-3-week paclitaxel), upon completion of the paclitaxel course, were treated with standard doses FAC.
This report is likely to be just one of several that might come from this trial. Short-term outcomes (clinical response, which was equivalent, and pathologic CR rate, which favored the weekly paclitaxel schedule) are used as surrogates of the more meaningful data (disease free and overall survival) for which it is likely data will be available soon. Nonetheless, it is likely that pCR will correlate with longer disease free and overall survival, as has been demonstrated previously.2
Thus, although the study design presents logistical problems for rigorous analysis, it is likely that weekly neoadjuvant paclitaxel will prove superior to the once-every-3-week schedule when the final reports are in and the findings are confirmed by other trials. It should be noted, however, that the dose and schedules chosen, particularly the 24 hour infusion of paclitaxel employed in the once-every-three-week schedule, but also in FAC, may be a bit outdated, having given way to the shorter infusion times for q3-week paclitaxel (3 hours) and the more conveniently administered doxorubicin/cyclophosphamide regimens.
References
1. Seideman AD. Gemcitabine and docetaxel in metastatic breast cancer. Oncology (Williston Park). 2004;18(14 Suppl 12):13-16.
Paclitaxel, administered weekly, compared to once-every-3-weeks in a trial of primary systemic (neoadjuvant) treatment for operable breast cancer was shown by Green and colleagues at M.D. Anderson and Brown University to provide comparable clinical responses but superior rates of pathological complete response (pCR) and breast conservation. Both the weekly and q3 week regimens were followed by 4 cycles of fluorouracil/doxorubicin/cyclophosphamide (FAC).Subscribe Now for Access
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