A randomized trial of chemotherapy (L-PAM vs CMF) and irradiation for node positive breast cancer

Abstract

158 evaluable patients with stage II, lymph node positive, carcinoma of the breast were randomized to adjuvant therapy with either melphalan (L-PAM) or cyclophosphamide, methotrexate, and fluorouracil (CMF) after mastectomy. In addition, patients were randomized to be treated with or without post-operative irradiation therapy (RT) in addition to their chemotherapy. At a median follow-up time of 11 years, there is no difference in time to relapse (P = 0.69) or survival (P = 0.55) among the four treatment groups. Multivariate analysis including treatment arm, age, race, tumor size, histologic type, performance status, time to onset of treatment, menopausal status, and number of positive nodes, revealed that only the number of positive nodes (less than 4 vs greater than or equal to 4) was related to disease-free and overall survival. Ten year relapse-free survival for patients with less than 4 positive nodes compared to those with greater than or equal to 4 positive nodes was 63% versus 30%, and overall survival 63% versus 41%, respectively. Patients who received post-operative radiation therapy had significantly less local recurrence than those treated with chemotherapy alone (P = 0.03) but without improvement in relapse-free or overall survival. In this trial, post-operative radiation therapy when added to chemotherapy decreased the risk of local recurrence without adverse effects on survival. Treatment outcome was not influenced by chemotherapy regimen, but differences may have been obscured by the small sample size.

A High-Throughput Pharmaceutical Screen Identifies Compounds with Specific Toxicity against BRCA2-Deficient Tumors

“…Especially poorly differentiated tumors showed favorable response to single-agent melphalan therapy[36]. However, regimens using melphalan or chlorambucil did not perform any better than the standard of care combination treatment at the time, cyclophosphamide, methotrexate and 5-fluorouracil (CMF)[37, 38], and these alkylators were therefore abandoned as treatment options. While nimustine is mainly used in Japan for the treatment of malignant glioma, we are not aware of any clinical trials with this compound in breast cancer patients.…”

Prognostic Significance of Apex Axillary Invasion for Locoregional Recurrence and Effect of Postmastectomy Radiotherapy on Overall Survival in Node‐Positive Breast Cancer Patients

“…Therefore, attaining maximal initial locoregional tumor control is necessary to achieve the best possible survival in patients with positive axillary nodes treated with mastectomy and systemic therapy [18]. The literature is consistent in reporting that postmastectomy irradiation substantially reduces the risk of locoregional recurrences [1][2][3][4][5][6][7][8][19][20][21]. Defining the prognostic factors for LRR is of utmost importance in selecting the patients who are most likely to benefit from adjuvant radiotherapy.…”

Coexpression of rat glutathione S-transferase A3 and human cytidine deaminase by a bicistronic retroviral vector confers in vitro resistance to nitrogen mustards and cytosine arabinoside in murine fibroblasts

“…Chlorambucil and Ara-C are part of an effective regimen for the treatment of low-grade non-Hodgkin's lymphomas; 34 high-dose melphalan and high-dose Ara-C are both active in advanced non-Hodgkin's lymphomas; 35,36 and finally, melphalan and gemcitabine are active against ovarian and breast cancers. [37][38][39][40] In addition, Ara-C, a drug that inhibits DNA repair, has been reported to enhance the cytotoxic activity of melpha-lan. 41 Hence, conferring chemoprotection against the hematotoxicity produced by nitrogen mustards and cytosine nucleoside analogs could potentially allow the safe use of desirable drug combinations that might otherwise cause unacceptable hematopoietic toxicity.…”