Impact of Consolidation Radiotherapy in Patients With Advanced Breast Cancer Treated With High-Dose Chemotherapy and Autologous Bone Marrow Rescue

1999 ◽  
Vol 17 (3) ◽  
pp. 887-887 ◽  
Author(s):  
Dennis L. Carter ◽  
Lawrence B. Marks ◽  
Joseph M. Bean ◽  
Gloria Broadwater ◽  
Atif Hussein ◽  
...  

PURPOSE: To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1988 and 1994, 425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT−). The assignment of RT was not randomized. The RT+ and RT− groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated. RESULTS: Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT− patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT− groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT− groups, respectively (P = .20). CONCLUSION: Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.

1993 ◽  
Vol 11 (3) ◽  
pp. 478-484 ◽  
Author(s):  
M J Kennedy ◽  
G B Vogelsang ◽  
R A Beveridge ◽  
E R Farmer ◽  
V Altomonte ◽  
...  

PURPOSE We investigated if graft-versus-host disease (GVHD), which is associated with an antitumor effect, could be induced in women with advanced breast cancer by treatment with cyclosporine (CSA) following reinfusion of purged autologous marrow after treatment with high-dose chemotherapy and defined the toxicities of this approach. PATIENTS AND METHODS Fifty-one women with advanced breast cancer responding to therapy were treated with escalating doses of CSA (1.0, 2.5, or 3.75 mg/kg/d) for 28 days following high-dose chemotherapy and autologous bone marrow transplantation and monitored for induction of GVHD and toxicity of therapy. RESULTS GVHD was induced in a dose-dependent fashion in 14%, 68%, and 92% of patients at each dose level, respectively, a median of 15 days following autologous marrow reinfusion. GVHD was clinically mild and limited to skin. Toxicity was acceptable, with two deaths within 50 days of marrow reinfusion. Statistically significant increases in maximum creatinine and bilirubin levels were seen at all dose levels when compared with similarly treated historic controls who did not receive CSA. Time to last platelet transfusion was significantly delayed in patients treated at the highest dose. CONCLUSION GVHD can be safely induced by treatment with CSA in women with advanced breast cancer who are receiving high-dose alkylating agents and autologous bone marrow transplantation. The toxicity of this approach is acceptable. Evidence of antitumor efficacy awaits further investigation.


1994 ◽  
Vol 12 (2) ◽  
pp. 342-346 ◽  
Author(s):  
R Ghalie ◽  
C M Richman ◽  
S S Adler ◽  
M A Cobleigh ◽  
A D Korenblit ◽  
...  

PURPOSE We investigated the role of high-dose chemotherapy and autologous bone marrow transplantation (ABMT) as the initial systemic treatment in patients with hormone-unresponsive metastatic breast cancer. We studied a regimen involving a split-course schedule using sequential administration of two pairs of alkylating agents separated by 5 days of rest. The rest period was intended to provide time for recovery from the treatment-immediate adverse effects, thereby allowing further dose escalation. PATIENTS AND METHODS The treatment consisted of thiotepa 225 to 300 mg/m2/d (days - 11 to -9), cisplatin 50 to 100 mg/m2/d (days - 11 and -3), and cyclophosphamide 60 mg/kg/d (days - 3 and -2). Dose escalation was performed in the initial 15 patients before reaching dose-limiting toxicities. When feasible, responding patients received posttransplant irradiation to sites of residual or prior bulky disease. Patients with bone marrow or CNS involvement, prior pelvic irradiation, or age greater than 55 years were excluded. RESULTS Thirty-nine patients with measurable or assessable tumor were enrolled: 23 with visceral metastases, 11 with only soft tissue disease, and five with skeletal involvement. Twenty-five patients had received no chemotherapy for metastatic disease before transplantation. The dose-limiting toxicities of this therapy were renal and gastrointestinal. Six patients died from complications: four of a fungal infection and two of hemorrhage. A complete response was achieved in 14 patients (36%), three of whom are free of disease at 79+, 55+, and 40+ months after transplantation. Ten of 25 patients not treated with standard-dose chemotherapy for metastatic disease achieved a complete response (40%). The three patients in continuous remission were in the untreated relapse group. CONCLUSION This single high-dose treatment achieved a relatively high complete response rate in patients with metastatic breast cancer and may have cured some of them. On the other hand, the split-course dose schedule as tested here did not permit significant dose-intensification.


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