Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five-year results.

Gianni, Alessandro M.; Siena, Salvatore; Bregni, Marco; Nicola, Massimo Di; Orefice, Sergio; Cusumano, F; Salvadori, B; Luini, Alberto; Greco, Maria Raffaella; Zucali, R; Rilke, F; Zambetti, Milvia; Valagussa, Pinuccia; Bonadonna, Gianni

doi:10.1200/jco.1997.15.6.2312

Cited by 166 publications

(100 citation statements)

References 26 publications

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“…HD thiotepa has been associated with a 5% cardiac toxicity in two studies, 54,55 while other series did not confirm these findings. 8,25 HD ifosfamide cardiotoxicity is reported in only two studies more than 20 years old. 56,57 Anecdotal evidence is reported for HD carmustine-associated cardiac toxicity.…”

Section: Other Chemotherapeutic Agentsmentioning

confidence: 99%

“…10 However, in recent years, the percentage of patients receiving singleagent HD cyclophosphamide up to 7 g/m 2 or 200 mg/kg experiencing cardiotoxicity has diminished to nearly zero with the adoption of multifractionated schedule of administration. 4,5,[7][8][9]25 Available evidence indicates that singleagent HD cyclophosphamide-associated cardiac toxicity is dose and schedule dependent, and it is not related to the cumulative drug dose. 13,16,21 No pharmacokinetic parameter has been consistently associated with cardiotoxicity, although a significant inverse association between a reduced HD cyclophosphamide area under the curve (AUC) (ie accelerated clearance due to an increased conversion to active metabolites) and cardiotoxicity was found in three independent studies, 17,26,27 but not confirmed in a larger one.…”

Section: Cardiac Toxicity Due To Conditioning Regimenmentioning

confidence: 99%

“…Indeed, association of obesity with cardiac toxicity can be spotted throughout the literature. 25,50 However, no uniform clinical dosing guidelines have been established, leading to a marked variability among institutions according to the method of dose adjustment used. 94 As a practical approach, in our experience and that of other groups, reduction of HD cyclophosphamide dosage in patients whose actual weight exceeds by 420% the ideal weight is a safety measure that does not affect the efficacy of chemotherapy and minimizes the risk of toxicity.…”

Section: Radiation Treatmentmentioning

confidence: 99%

“…Particularly, the combination of HD melphalan and fludarabine has been used to condition patients with advanced hematologic malignancies. 59 HD melphalan has not been shown to be cardiotoxic, 7,9,25,50,[60][61][62][63][64] with the exception of atrial fibrillation. [65][66][67] Fludarabine has also been rarely associated with cardiac dysfunction.…”

Section: Other Chemotherapeutic Agentsmentioning

confidence: 99%

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Cardiac toxicity of high-dose chemotherapy

Morandi

Ruffini

Benvenuto

et al. 2004

Bone Marrow Transplant

148

104

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Summary:Cardiac toxicity is an uncommon but potentially serious complication of high-dose (HD) chemotherapy and little is known about incidence, severity and underlying mechanisms. We have systematically reviewed the literature of the last 30 years to summarize and appraise the published evidence on cardiac toxicity associated with HD chemotherapy. HD cyclophosphamide-containing regimens have been most commonly associated with cardiac toxicity, with a progressively decreasing incidence over time. Dosage, application regimens and coadministration of other chemotherapeutic agents emerged as risk factors. While cardiac toxicity has been rarely associated with other cytotoxic drugs, an unexpected incidence of severe cardiotoxicity resulted from reduced-intensity conditioning regimens containing melphalan and fludarabine. Predictive value of cardiologic examination of patients is limited, and patients with a slight depression of cardiac performance could tolerate HD chemotherapy. Clinical examination, resting electrocardiography and dosage adjustment in overweight patients remain the mainstay of prevention, with bidimensional echocardiography (2D echo) for patients with a history of anthracycline exposure. Strategies to decrease the long-term negative impact of anthracycline administration on cardiac performance are being investigated. New 2D echo-based techniques and circulating markers of cardiac function hold promise for allowing identification of patients at high risk for and early diagnosis of cardiac toxicity.

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Section: Other Chemotherapeutic Agentsmentioning

confidence: 99%

Section: Cardiac Toxicity Due To Conditioning Regimenmentioning

confidence: 99%

Section: Radiation Treatmentmentioning

confidence: 99%

Section: Other Chemotherapeutic Agentsmentioning

confidence: 99%

See 2 more Smart Citations

Cardiac toxicity of high-dose chemotherapy

Morandi

Ruffini

Benvenuto

et al. 2004

Bone Marrow Transplant

148

104

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“…The OS is 68% [59]. Updated data from the second study discuss 67 patients treated with high-dose sequential cyclophosphamide, methotrexate, and melphalan with a median follow-up of 48.5 months and a lead follow-up of 78 months [60]. Actuarial relapse-free survival (RFS) is 57% and OS 70%.…”

Section: Hdc For High-risk Primary Breast Cancermentioning

confidence: 99%

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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Long term follow-up of women treated with 16-week, dose-intensive adjuvant chemotherapy for high risk breast carcinoma

Mikhak¹,

Zahurak²,

Abeloff³

et al. 1999

Cancer

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Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five-year results.

Abstract: HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.

Cited by 166 publications

References 26 publications

Cardiac toxicity of high-dose chemotherapy

Cardiac toxicity of high-dose chemotherapy

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

Long term follow-up of women treated with 16-week, dose-intensive adjuvant chemotherapy for high risk breast carcinoma

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