scholarly journals Targeted radiotherapy to the skeleton using 166Ho-DOTMP with autologous stem cell transplantation for patients with bone-only metastatic breast cancer

2005 ◽  
Vol 11 (2) ◽  
pp. 84-85 ◽  
Author(s):  
R.E. Champlin ◽  
D. Booser ◽  
G. Rondon ◽  
P.A. Williams ◽  
R. Wendt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Metastatic Breast Cancer ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Metastatic Breast ◽  
Targeted Radiotherapy

Randomized Trial of Single Compared With Tandem High-Dose Chemotherapy Followed by Autologous Stem-Cell Transplantation in Patients With Chemotherapy-Sensitive Metastatic Breast Cancer

2006 ◽  
Vol 24 (24) ◽  
pp. 3919-3926 ◽  
Author(s):  
Nicolaus Kröger ◽  
Markus Frick ◽  
Oleg Gluz ◽  
Svjetlana Mohrmann ◽  
Bernd Metzner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Metastatic Breast Cancer ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival

Purpose To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients. Patients and Methods Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation. Results One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm. The rate of complete remission on an intent-to-treat-basis was 33% in the single-dose HDT arm and 37% in the tandem HDT arm (P = .48). The median progression-free survival times in single and tandem HDT arms were 9.4 and 11.2 months, respectively (one-sided P = .06; two one-sided P = .12), whereas median overall survival time tended to be greater after single versus tandem HDT (29 v 23.5 months, respectively; P = .4). In a multivariate analysis for progression-free survival, tandem HDT (hazard ratio [HR] = 0.71; 95% CI, 0.52 to 0.98; P = .03) and achievement of complete remission after induction chemotherapy (HR = 0.59; 95% CI, 0.37 to 0.96; P = .03) were factors for a better progression-free survival, whereas the factor of three or more sites of metastases (HR = 1.66; 95% CI, 1.12 to 2.47; P = .01) was associated with a worse progression-free survival. Conclusion Despite a trend of improved progression-free survival, tandem HDT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT.

Targeted Radiotherapy to the Skeleton Using 166Ho-DOTMP with Autologous Stem Cell Transplantation for Patients with Bone-Only Metastatic Breast Cancer.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5239-5239 ◽  
Author(s):  
Richard Champlin ◽  
Daniel Booser ◽  
Gabriela Rondon ◽  
Patricia Williams ◽  
Richard Wendt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Therapeutic Dose ◽  
Metastatic Breast ◽  
Fish Analysis ◽  
Targeted Radiotherapy

Abstract The skeleton is the most frequent site of metastatic disease in breast cancer, involving cortical and trabecular bone with or without extension into adjacent bone marrow. A subset of breast cancer patients develop bone dominant disease without metastases to other organs over a prolonged period of time. An attractive strategy is to utilize bone targeted radiotherapy to address this site of disease with minimal systemic toxicity. This study was designed to determine the safety and preliminary efficacy of 166Ho-DOTMP, which localizes to bone providing radiation to adjacent marrow and malignant cells. The limiting toxicity is myelosuppression, which can be overcome by autologous stem cell transplantation. We studied this strategy in subjects with breast cancer metastatic to confined to the bone. Treatment occurred between 1997 and 1999. Subjects were eligible if they were <65 years of age, had bone only disease, had an estrogen receptor negative tumor or had failed hormonal therapy. A 30 mCi tracer dose was administered to assess targeting and to allow the therapeutic dose to be calculated. If uptake was adequate, a therapeutic dose was to be administered in one of 2 dose levels, receiving 22 Gy (n=3) or 28 Gy (n=3). Treatment was followed by autologous stem cell transplantation when the ongoing radiation dose to marrow was <1 cGy/hour. The 6 subjects received a median of 1548 mCi (range 870 2065 mCi) of 166Ho DOTMP. There was selective uptake in the bone, particularly in sites of osteoblastic metastases, with unbound drug cleared into the urine. The most common toxicities seen during active treatment were mild nausea and vomiting. None of the patients experienced grade >3 acute toxicity aside from the expected profound myelosuppression. All subjects treated in the trial had prompt trilineage hematologic recovery post transplant. Two patients developed hemorrhagic cystitis at approximately two years following therapy which resolved in both patients. One of these patients also had GI bleeding and pseudomembranous colitis unrelated to the 166Ho DOTMP treatment. One subject developed MDS, but was found to have a pre-existing trisomy 8 by FISH analysis from the peripheral blood stem cell product collected prior to treatment on this study. Two patients achieved complete remission and remain progression-free over 5 years following study entry. Four relapsed and died of progressive disease; all recurred in extraosseous sites with two also having disease in the bone marrow. Median time to progression was 10 months. Conclusions: Treatment with 166Ho DOTMP delivers targeted radiotherapy to the skeleton with an acceptable toxicity profile. Two of 6 patients with bone-only metastases achieved sustained complete responses. Further studies are warranted to evaluate this strategy for treatment of bone metastases.

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