Docetaxel/Vinorelbine Among Most Active Regimens Ever Tested in Neoadjuvant Setting

CHARLOTTE, North Carolina—Dose-intense, dose-dense neoadjuvant docetaxel (Taxotere) /vinorelbine (Navelbine) produced a pathologic complete response rate of 36% in women with locally advanced breast cancer, making the combination among the most active ever tested in this setting, according to investigator Steven A. Limentani, MD. Preliminary study results also suggest the regimen is safe and well tolerated.

"The goal (of neoadjuvant therapy), of course, is to have a high pathologic complete response, because that has been well correlated with overall survival and disease-free survival," Dr. Limentani said. He is co-director of the breast cancer program, Blumenthal Cancer Center, Carolinas Medical Center, Charlotte, North Carolina.

Two Ongoing Trials

The data Dr. Limentani reported come from two separate ongoing neoadjuvant trials. In the first, women with stage IIA-IIIB and locoregional stage IV breast cancer receive docetaxel (60 mg/m²) and vinorelbine (45 mg/m²) with G-CSF and quinolone prophylaxis every 2 weeks for six cycles. The second trial includes women with stage IIB-IIIB and locoregional stage IV breast cancer and HER2 overexpression; they receive the same docetaxel/vinorelbine regimen plus weekly trastuzumab (Herceptin). After surgery, patients in both trials receive doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) every 3 weeks for four cycles.

Forty-seven patients (age range 27 to 66 years) have been enrolled, including eight who received trastuzu-mab, Dr. Limentani reported. The average tumor size was 6.5 cm, and about 75% of patients had clinically palpable nodes.

Of 36 patients evaluable for efficacy, 18 (50%) had a clinical complete response, while another 17 (47%) had a partial response, for an overall response rate of 97%. One patient (3%) had progression of disease.

Pathologic response by National Surgical Adjuvant Breast and Bowel Project (NSABP) criteria was seen in 12 of 33 patients evaluated (36%). This exceeds the rate seen in the NSABP B-27 protocol (sequential docetaxel added to doxorubicin and cyclophosphamide [Cytoxan, Neosar] vs doxorubicin and cyclophosphamide alone). "The critical finding here is that using 3 months of therapy, we have a pathologic complete response rate of 36%, which is higher than what was seen in B-27, with half the duration of therapy and no anthracycline, in a group of patients who were far more advanced," Dr. Limentani noted.

Preliminary results of the B-27 protocol were presented in 2001 at the San Antonio Breast Cancer Symposium [Br Ca Res Treat; 69:210 (abstract 5, 2001]. According to that report, docetaxel added to neoadjuvant doxorobucin and cyclophosphamide produced a pathologic complete response rate of 25.6%, essentially double what was seen in patients who received only doxorubicin and cyclophosphamide (13.7%).

Toxicities Minimal

Overall, toxicities have been minimal, and the regimen has been well tolerated by all patients, according to Dr. Limentani. Relative delivered dose intensity was 96.1% for docetaxel and 95.1% for vinorelbine. Grade 3/4 hematologic toxicity so far includes neutropenic fever in 10 of 47 patients (21%). No patients have had serious infections.

Serious nonhematologic toxicities have included two cases of constipation (not significant since investigators began incorporating prophylactic laxatives into the treatment schema), one urinary tract infection and one case of hypertension.

Based on these promising results, docetaxel/vinorelbine deserves more study as a potential "new standard" for the treatment of high-risk breast cancer, Dr. Limentani said. Furthermore, moving doxorubicin back into the neoadjuvant part of the regimen could push pathologic complete response rates even higher.