High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer.

1989 ◽  
Vol 7 (12) ◽  
pp. 1824-1830 ◽  
Author(s):  
S F Williams ◽  
R Mick ◽  
R Desser ◽  
J Golick ◽  
J Beschorner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Induction Chemotherapy ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Complete Response ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Stage Iv Breast Cancer ◽  
Autologous Stem Cell Rescue

We designed a phase II study to determine whether induction chemotherapy (CT) consisting of leucovorin, vincristine, methotrexate, doxorubicin, and cyclophosphamide (LOMAC) followed by high-dose intensification chemotherapy (ICT) with cyclophosphamide, thiotepa, and autologous stem cell rescue (ASCR) could increase the complete response (CR) rate and survival in women with stage IV breast cancer. Twenty-nine women were enrolled on study; 16 patients had received prior adjuvant chemotherapy and no patient had received chemotherapy for stage IV disease. Two patients were found to be ineligible and excluded from further analysis. Of the 27 patients treated, four (15%) obtained a CR and 15 (56%) a partial response (PR) after LOMAC induction, for an overall response rate of 70%. Of the 22 patients treated with ICT, 12 patients had a CR, and nine were in PR after induction and converted to CR after ICT. The toxicities included nausea/vomiting, mucositis, diarrhea, dermatitis, alopecia, and infections secondary to neutropenia. The 1-year survival is 60%; the median has not yet been reached. The time to treatment failure for patients on study is 10 months. The treatment approach of ICT and ASCR following induction chemotherapy can lead to an improved CR rate in stage IV breast cancer. How this increased CR rate leads to a prolonged disease-free survival requires further follow-up.

High-dose chemotherapy with autologous stem cell rescue in breast cancer

1996 ◽  
Vol 37 (3) ◽  
pp. 277-289 ◽  
Author(s):  
Robert O. Dillman ◽  
Neil M. Barth ◽  
Shankar K. Nayak ◽  
Cristina DeLeon ◽  
Audrey O'Connor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Autologous Stem Cell Rescue

Association of polymorphic drug metabolizing enzymes (DME) with outcomes in breast cancer patients treated on the ECOG 2190/Intergroup 0121 (E2190/Int0121) study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 596-596
Author(s):  
P. P. Gor ◽  
R. J. Gray ◽  
M. Horn ◽  
T. R. Rebbeck ◽  
P. A. Gimotty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cox Regression ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Stem Cell Rescue

596 Background: Disparate outcomes of breast cancer patients after adjuvant chemotherapy may be influenced by variation in drug metabolism due to genetic polymorphisms in DME. Cyclophosphamide and thiotepa require activation by cytochrome P450 (CYP) and detoxification by glutathione-S-transferase, two highly polymorphic enzymes. We hypothesized that variants in CYP3A4(*1B), GSTM1 and GSTT1 would impact survival outcomes after adjuvant chemotherapy, with effects potentially modulated by chemotherapy dose. Methods: We performed a retrospective cohort study of patients enrolled on E2190/Int0121, a randomized trial of cyclophosphamide (C), doxorubicin (A), and fluorouracil (F) versus CAF + high dose chemotherapy (HDC) using cyclophosphamide and thiotepa followed by stem cell rescue; disease-free survival (DFS) and overall survival (OS) were equivalent in the clinical trial. PCR-based methods were used to genotype hematologic stem cells. Hazard ratios for genotypes were obtained using Cox regression. Results: Stem cell samples and clinical data from August 1, 1991 through August 1, 2005 were available for 347/540 of patients enrolled; 151 patients on CAF and 196 on CAF + HDC arms, respectively. Median follow-up was 9.8 years. See table . CYP3A4*1B allele carriers had significantly poorer DFS (HR 1.84) in the combined cohort and CAF arm (HR 1.87), but not in the HDC arm; OS was not significant by CYP3A4 genotype. GSTM1 null homozygotes in the combined cohort and HDC arm had significantly better DFS (HR 0.70 and 0.66, respectively) and OS (HR 0.67 and 0.57, respectively), but not in the CAF arm. GSTT1 null homozygotes had significantly worse DFS (HR 2.3) and OS (2.02) in the CAF arm, but not in the HDC arm or combined cohort. Conclusions: In the overall E2190/Int0121 cohort, polymorphisms in activating (CYP3A4*1B) and inactivating (GSTM1) DME significantly impact DFS and OS. The detrimental effect of GSTT1 in the CAF arm appears to be ameliorated by HDC. [Table: see text] No significant financial relationships to disclose.

High-dose consolidation therapy with autologous stem-cell rescue in stage IV breast cancer: follow-up report.

1992 ◽  
Vol 10 (11) ◽  
pp. 1743-1747 ◽  
Author(s):  
S F Williams ◽  
T Gilewski ◽  
R Mick ◽  
J D Bitran
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Median Time ◽  
Metastatic Breast ◽  
Stage Iv ◽  
High Dose ◽  
Dose Intensification ◽  
Stem Cell Rescue ◽  
Stage Iv Breast Cancer ◽  
Time To Treatment Failure

PURPOSE Fifty-nine patients with newly diagnosed metastatic breast cancer were treated with induction chemotherapy followed by high-dose intensification and autologous stem-cell rescue (ASCR) to determine therapeutic efficacy. PATIENTS AND METHODS Induction consisted of cyclophosphamide, doxorubicin, vincristine, and methotrexate with leucovorin rescue (LOMAC) in 27 patients, or fluorouracil, cisplatin, doxorubicin, and cyclophosphamide (FCAP) in 32 patients. Intensification after LOMAC was cyclophosphamide and thiotepa (CyTepa) with ASCR, and after FCAP it was cyclophosphamide, thiotepa, and carmustine (BCNU) in all but eight patients who received CyTepa. RESULTS Median survival from study entry for the entire group was 13.3 months. Median time to progression from reinfusion for the 45 patients who underwent intensification was 7.5 months. After LOMAC and intensification, there were 12 complete responses (CR) (nine partial responses [PRs] after induction converted to CRs). Responses after FCAP and intensification were eight CRs (two PRs after induction converted to CRs). Median time to treatment failure from reinfusion was 5.4 months for LOMAC and intensification, and was 10.5 months for FCAP and intensification. Median survival from study entry was 15.1 months for all 27 LOMAC patients and 9.3 months for all 32 FCAP patients. Median time to treatment failure from reinfusion for 11 patients who were CRs at intensification has not been reached and is more than 13 months compared with a median of 5.5 months for the 23 patients in partial remission at intensification. CONCLUSIONS High-dose intensification therapy has led to increased CR rates in metastatic breast cancer. The role of such therapy in the treatment of stage IV breast cancer requires further refinement.

High-Dose Cyclophosphamide, Carboplatin, and Etoposide with Autologous Stem Cell Rescue in Patients with Breast Cancer

1996 ◽  
Vol 19 (2) ◽  
pp. 169-173 ◽  
Author(s):  
Margarida deMagalhaes-Silverman ◽  
Witold B. Rybka ◽  
Barry Lembersky ◽  
Elana J. Bloom ◽  
John Lister ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Autologous Stem Cell Rescue
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