New strategies in marrow purging for breast cancer patients receiving high-dose chemotherapy with autologous bone marrow transplantation

1993 ◽  
Vol 26 (1) ◽  
pp. S19-S23 ◽  
Author(s):  
Elizabeth J. Shpall ◽  
Salomon M. Stemmer ◽  
Scott I. Bearman ◽  
Susan Myers ◽  
Malcolm Purdy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Marrow Purging ◽  
Autologous Bone ◽  
New Strategies

Treatment of metastatic breast cancer with a split-course high-dose chemotherapy regimen and autologous bone marrow transplantation.

1994 ◽  
Vol 12 (2) ◽  
pp. 342-346 ◽  
Author(s):  
R Ghalie ◽  
C M Richman ◽  
S S Adler ◽  
M A Cobleigh ◽  
A D Korenblit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Metastatic Breast Cancer ◽  
Autologous Bone Marrow Transplantation ◽  
Metastatic Breast ◽  
Autologous Bone Marrow ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Autologous Bone

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.

scholarly journals Amifostine (WR-2721) shortens the engraftment period of 4- hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3132-3137 ◽  
Author(s):  
EJ Shpall ◽  
SM Stemmer ◽  
L Hami ◽  
WA Franklin ◽  
L Shaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Ex Vivo ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Autologous Bone

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty- three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high- dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.

Sequential prophylactic oral and empiric once-daily parenteral antibiotics for neutropenia and fever after high-dose chemotherapy and autologous bone marrow support.

1994 ◽  
Vol 12 (5) ◽  
pp. 1005-1011 ◽  
Author(s):  
C Gilbert ◽  
B Meisenberg ◽  
J Vredenburgh ◽  
M Ross ◽  
A Hussein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
Sepsis Syndrome ◽  
Ease Of Use ◽  
High Dose ◽  
Once Daily ◽  
Autologous Bone

PURPOSE We studied the effectiveness of prophylactic oral ciprofloxacin and rifampin on fever prevention in patients undergoing autologous bone marrow transplantation (ABMT) for breast cancer. Furthermore, we evaluated the toxicity and efficacy of empiric once-daily vancomycin and tobramycin for febrile neutropenia. PATIENTS AND METHODS Ninety-nine assessable women received prophylactic ciprofloxacin and rifampin after high-dose chemotherapy (HDC) for advanced or high-risk primary breast cancer supported with either bone marrow and peripheral-blood progenitor cells (PBPCs) or bone marrow purged with chemotherapy and monoclonal antibodies. Neutropenic fever was treated with empiric once-daily vancomycin and tobramycin. Patients were compared with historic controls treated with the identical HDC and bone marrow support regimen. RESULTS In patients treated with bone marrow and PBPCs, the incidence of fever during neutropenia was reduced by ciprofloxacin and rifampin from 98% to 57%. Documented infections were reduced from 42% to 13% (P < .01) and bacteremia from 18% to 0% (P < .001). In purged bone marrow recipients, the overall infection rate decreased from 74% to 17% (P < .001), and bacteremia from 29% to 7%. (P = .02). No patient developed breakthrough bacteremia or sepsis syndrome while on study. Serum creatinine level greater than 1.8 g/dL was noted in 7% of controls and 10% of study patients. Increased ototoxicity was not encountered with the higher peak concentrations of vancomycin and tobramycin. CONCLUSION The therapeutic strategy of ciprofloxacin and rifampin followed by once-daily vancomycin and tobramycin markedly reduced the incidence of infection and virtually eliminated bacteremia in both purged and nonpurged bone marrow recipients. Once-daily vancomycin and tobramycin was safe and effective and, because of the ease of use, facilitates outpatient management of ABMT patients.

scholarly journals Amifostine (WR-2721) shortens the engraftment period of 4- hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3132-3137 ◽  
Author(s):  
EJ Shpall ◽  
SM Stemmer ◽  
L Hami ◽  
WA Franklin ◽  
L Shaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Ex Vivo ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Autologous Bone

Abstract 4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty- three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high- dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.

High-Dose Chemotherapy With Autologous Bone Marrow Transplantation for the Treatment of Metastatic Breast Cancer

1992 ◽  
Vol 10 (10) ◽  
pp. 1655-1658 ◽  
Author(s):  
David M. Eddy
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Metastatic Breast Cancer ◽  
Bone Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Metastatic Breast ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Autologous Bone

Tables 1 to 4 contained errors in the report "High-Dose Chemotherapy With Autologous Bone Marrow Transplantation for the Treatment of Metastatic Breast Cancer" by Eddy (J Clin Oncol 10:657–670, 1992). They are reprinted here correctly in their entirety: Please see the PDF for Table.

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