Minimal toxicity and mortality in high-risk breast cancer patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin plus autologous marrow/stem-cell transplantation and comprehensive supportive care.

Holland, H. Kent; Dix, Suzanne P.; Geller, Robert B.; Devine, S M; Heffner, Leonard T.; Connaghan, D G; Hillyer, C D; Hughes, Larry; Miller, Robin Lin; Moore, Martha; Winton, EF; Wingard, John R.

doi:10.1200/jco.1996.14.4.1156

Cited by 51 publications

(32 citation statements)

References 21 publications

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“…These results are significantly better than historical or contemporary data obtained for similar prognosis patients receiving SDC. A number of other phase II trials have also reported encouraging results in high-risk primary disease [61][62][63][64]. ABMTR reported outcomes [43] in high-risk primary disease are consistent with the phase II reports.…”

Section: Hdc For High-risk Primary Breast Cancersupporting

confidence: 81%

High-Dose Chemotherapy and Peripheral Blood Progenitor Cell Transplantation in the Treatment of Breast Cancer

et al. 2000

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Each year in the USA, 180,000 new cases of breast cancer are diagnosed and about 44,000 women die of the disease. Current primary treatment consists of adjuvant chemotherapy and hormone therapy, and statistics show that combination chemotherapy favorably influences the outcomes in both node-negative and node-positive primary disease. However, a significant number of breast cancer patients succumb to the disease, and nearly every patient diagnosed with metastatic breast cancer will be dead within five years.High-dose chemotherapy (HDC) and peripheral blood progenitor cell transplantation (PBPCT) are based upon laboratory and clinical observations of the ability to modify growth properties of quiescent and replicating cancer cells. A large number of HDC and PBPCT regimens have been evaluated for treatment of metastatic breast cancer, and recent autologous bone marrow transplantation data indicate that three HDC regimens (CPB, CTCb and cytoxan and thiotepa) predominate. Unfortunately, negative media coverage surrounding and subsequent to the presentation of preliminary findings reported at the May 1999 American Society of Clinical Oncologists, that were not allowed adequate follow-up time for full analysis of treatment results, has had a detrimental effect on the ability to conduct trials in this area.Several randomized trials have been conducted in both the metastatic and high risk primary disease settings. Thorough analysis of these studies indicates an evaluable improvement in favor of HDC and PBPCT in three of the four randomized studies performed in metastatic breast cancer and two of the four high risk primary studies. Also, initial evaluations found that quality of life appeared comparable in patients receiving either HDC or not. Each randomized trial studied asks a different question and, depending on the intensity of HDC regimen, the intensity and duration of the standard dose chemotherapy control and the schedule of events in relation to induction chemotherapy, the outcomes may be quite variable. Still, certain general trends are indentifiable. HDC alone will not completely cure breast cancer and should be considered as part of an overall therapeutic plan. In some of these studies, significantly longer follow-up is required before definitive analysis can be completed. The Oncologist 2000;5:1-13

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Section: Hdc For High-risk Primary Breast Cancersupporting

confidence: 81%

High-Dose Chemotherapy and Peripheral Blood Progenitor Cell Transplantation in the Treatment of Breast Cancer

et al. 2000

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“…The toxicity appears equivalent to previously published reports in women receiving autotransplants for breast cancer. [11][12][13][14] Although the number of subjects is small, the efficacy of autotransplant in these 13 men with high-risk breast cancer appears similar to results reported in women. 11,12 Outcomes of the patients with metastatic disease were disappointing, however only three patients were available for analysis.…”

Section: Discussionsupporting

confidence: 63%

Autotransplants in men with breast cancer

McCarthy

Hurd

Rowlings

et al. 1999

Bone Marrow Transplant

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Summary:The purpose of this study was to determine the outcome of high-dose therapy with autologous hematopoietic stem cell support (autotransplants) in men with breast cancer. We studied 13 men receiving autotransplants for breast cancer and reported to the Autologous Blood and Marrow Transplant Registry (ABMTR) by 10 centers. Six men had stage 2 breast cancer, four had stage 3, and three had metastatic breast cancer. Of twelve tumors tested, all were estrogen receptor positive. Median age at transplant was 50 years. The most common conditioning regimen was cyclophosphamide, thiotepa and carboplatin (n = 5); the remaining eight men received other alkylator-based regimens. Three men received bone marrow, eight received blood stem cells, and two received both for hematopoietic support. All patients had hematopoietic recovery. There were no unexpected regimen-related toxicities. Of 10 men receiving autotransplants as adjuvant therapy, three relapsed 3, 5 and 50 months post-transplant and died 16, 19 and 67 months post-transplant. Seven of 10 are disease-free with median follow-up of 23 months (range 6-50 months). Of three men treated for metastatic breast cancer, one had progressive disease and two recurrent disease at 6, 7 and 16 months post-transplant. In conclusion, results of autotransplants for male breast cancer appear similar to those reported for women receiving autotransplants for breast cancer. Keywords: male breast cancer; autotransplant Male breast cancer accounts for fewer than 1% of all breast cancers. The annual incidence is Ͻ1 per 100 000 males. 1,2 Stage at diagnosis is generally more advanced than in women, possibly as a result of delays in diagnosis. Anatomic factors may also contribute. 3 The median age of men with breast cancer is 5 to 10 years older than women with breast cancer. 1-7 While 64% of premenopausal and 75% of post-menopausal women have estrogen receptor (ER) positive cancers and 58% and 53%, respectively, have progesterone receptor (PR) positive tumors, according to a large study by Clark and colleagues, 8 80-90% of men have ER and PR positive breast cancer. [1][2][3][4][5][6][7] Recent advances in the molecular biology of breast cancer have allowed detection of differences in the BRCA1 and BRCA2 mutations in hereditary and spontaneously occurring female and male breast cancers (reviewed in Refs 9 and 10).The standard therapy of breast cancer in men is similar to treatment in women, including surgery, radiation, hormone therapy and chemotherapy. 1-7 Some investigators report outcomes in men to be the same as in women, when patients are matched for histopathology, receptor state and disease stage. [3][4][5][6] Others suggest that men have poorer outcomes than women despite lower histologic grade, high ER content and small size. 6

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“…28 Carboplatin has also been used as a part of CTCb and ICE regimens for treatment of various solid tumors with HDC and autologous PBSCT. 3,[28][29][30][31] Calvert et al 47 have documented the importance of dosing by a calculated target formula which compensates for renal function, age and gender when conventional doses of carboplatin are administered. It has been demonstrated that estimated AUC values of carboplatin in several studies overlapped with dosing on a mg/m 2 basis.…”

Section: Upnmentioning

confidence: 99%

“…3 Carboplatin as a part of ICE (ifosfamide, carboplatin and etoposide) and CTCb (cyclophosphamide, thiotepa, carboplatin) HDC regimens has been used for the treatment of various solid tumors with autologous PBSCT. 3,[27][28][29][30][31] Based on these observations, we hypothesized that a HDC regimen of thiotepa, melphalan and carboplatin would have substantial antitumor activity. We report the results of a dose escalation study of carboplatin administered with a fixed dose of 500 mg/m 2 thiotepa and 100 mg/m 2 melphalan to determine the maximum tolerated dose (MTD) in patients with refractory malignancies.…”

mentioning

confidence: 99%

A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies

Demirer

İlhan

Mandel

et al. 2000

Bone Marrow Transplant

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Summary:The purpose of this study was to determine the maximum tolerated dose of carboplatin administered with 500 mg/m 2 thiotepa and 100 mg/m 2 melphalan followed by autologous peripheral blood stem cell (PBSC) infusion in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose thiotepa (500 mg/m 2 , melphalan (100 mg/m 2 ) and escalating doses of carboplatin 900-1500 mg/m 2 ) followed by infusion of cryopreserved autologous PBSCs. The maximum tolerated doses were determined to be 500 mg/m 2 thiotepa, 100 mg/m 2 melphalan and 1350 mg/m 2 carboplatin. Two consecutive patients receiving 1500 mg/m 2 carboplatin experienced grade 3 mucositis and colitis. Ten patients were enrolled at the maximum tolerated dose and none had grade 3-4 regimen-related toxicity and mortality. All patients at this level experienced grade 1-2 mucositis, 90% grade 1-2 gastrointestinal toxicity, 30% grade 1-2 cardiac and renal toxicity, and 10% experienced grade 1 hepatic toxicity. The median time to achieve a granulocyte count of 0.5 × 10 9 /l was 9 days (range 7-12 days) and platelet count of 20 × 10 9 /l was 10 days (range 7-15 days). Of eight patients with stage IV refractory breast cancer, even were evaluable for response, one patient on day 75 will be evaluated soon. Five of seven (71.5%) evaluable patients achieved a complete remission (CR) and two had no response. Of seven patients with non-Hodgkin's lymphoma (n = 4) or Hodgkin's disease (n = 3), five achieved a CR (71.5%). Thiotepa, melphalan and carboplatin can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy-sensitive malignancies are warranted. Bone Marrow Transplantation (2000) 25, 697-703.

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Minimal toxicity and mortality in high-risk breast cancer patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin plus autologous marrow/stem-cell transplantation and comprehensive supportive care.

Cited by 51 publications

References 21 publications

High-Dose Chemotherapy and Peripheral Blood Progenitor Cell Transplantation in the Treatment of Breast Cancer

High-Dose Chemotherapy and Peripheral Blood Progenitor Cell Transplantation in the Treatment of Breast Cancer

Autotransplants in men with breast cancer

A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies

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