Long-term follow-up of a phase ii trial studying a weekly doxorubicin-based multiple drug adjuvant therapy for stage II node-positive carcinoma of the breast

Background. Combination chemotherapy improves outcomes in women with breast cancer (BC) that involves axillary nodes. This single-arm study aimed to evaluate the effectiveness of an intensive doxorubicin-based multi-drug regimen as adjuvant therapy in women with stage II, node positive breast cancer. Patients and methods. Between 7/80 and 8/85, 654 women, aged 25-73, who had a mastectomy for stage IIB BC were accrued. Patients with prior RT, chemotherapy, or surgical or radiation castration within 1 year of diagnosis were excluded. Treatment consisted of: 6 weekly courses of IV cyclophosphamide (C) 400 mg/m², doxorubicin (A) 10 mg/m², vincristine (V) 1 mg/m², fluorouracil (F) 400 mg/m², and a tapering course of prednisone followed by 12 courses of C 400 mg/m², A 20 mg/m², V 1 mg/m², F 400 mg/m² given every 2 weeks. Patients with estrogen receptor positive tumors received Tamoxifen 10 mg bid between weeks 8 and 30. Treatment did not exceed 8 months. Median follow-up is 13.1 years. Results. Six hundred thirty six patients are eligible. Fewer positive (+) nodes, premenopausal status, and positive progesterone receptor status are significantly (p < 0.05) associated with longer survival. At 10 years, 61% were relapse-free in the 1-3 +node group compared to 37 and 21% in the 4-9 and ≥ 10 +node groups, respectively (p = 0.0001). Relapse-free survival at 10 years is 50% for premenopausal and 45% for postmenopausal patients. Severe or life-threatening hematological toxicity was seen in 6/630 (<1%) patients. Four patients had severe (grade 3) neurotoxicity which resolved. No cardiac toxicity was observed. Conclusion. This adjuvant regimen compares favorably to other published adjuvant treatments with similar length of follow-up.