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

Frick, Michael; Gluz, Oleg; Mohrmann, Svjetlana; Metzner, Bernd; Jackisch, Christian; Ko, Yon; Lindemann, Hans Walter; Meier, Carl Richard; Lohrmann, Hans Peter; Ruffert, Ute; Hänel, Matthias; Bodenstein, H.; Neubauer, Andreas; Ehninger, Gerhard; Wolf, Hans Heinrich; Kolbe, Kathrin; Burock, K.; Zander, Axel R.; Nitz, Ulrike

doi:10.1200/jco.2005.04.0352

Cited by 11 publications

(5 citation statements)

References 22 publications

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“…Whether patients that receive tandem autologous HPCTs for malignancies other than myeloma are at increased risk for the development of autologous GVHD is not known, although, to date, this complication has not been reported to be increased in these patient populations. [34][35][36][37] In conclusion, this study demonstrates that severe steroid-refractory GVHD can occur after autologous HPCT for multiple myeloma. The incidence of this complication appears to be much higher in patients receiving second HPCTs suggesting that the repetitive exposure to high-dose chemotherapy may compromise reconstitution of regulatory networks that are necessary for the maintenance of self-tolerance.…”

Section: Discussionmentioning

confidence: 54%

Severe autologous GVHD after hematopoietic progenitor cell transplantation for multiple myeloma

Drobyski

Hari

Keever-Taylor

et al. 2008

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 54%

Severe autologous GVHD after hematopoietic progenitor cell transplantation for multiple myeloma

Drobyski

Hari

Keever-Taylor

et al. 2008

Bone Marrow Transplant

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“…In conclusion, due to the severe toxicity of HDC and the absence of a proven benefit, the final recommendation was to avoid the high-dose strategy outside of clinical trials (28). The recent randomized trials also confirmed, in unselected patient populations, the lack of a benefit from HDC either up front or as consolidation after response to standard induction chemotherapy (29–35). …”

Section: The Role Of Systemic Treatmentmentioning

confidence: 82%

International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured?

Pagani¹,

Senkus

Wood

et al. 2010

JNCI Journal of the National Cancer Institute

350

253

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A distinctive subset of metastatic breast cancer (MBC) is oligometastatic disease, which is characterized by single or few detectable metastatic lesions. The existing treatment guidelines for patients with localized MBC include surgery, radiotherapy, and regional chemotherapy. The European School of Oncology–Metastatic Breast Cancer Task Force addressed the management of these patients in its first consensus recommendations published in 2007. The Task Force endorsed the possibility of a more aggressive and multidisciplinary approach for patients with oligometastatic disease, stressing also the need for clinical trials in this patient population. At the sixth European Breast Cancer Conference, held in Berlin in March 2008, the second public session on MBC guidelines addressed the controversial issue of whether MBC can be cured. In this commentary, we summarize the discussion and related recommendations regarding the available therapeutic options that are possibly associated with cure in these patients. In particular, data on local (surgery and radiotherapy) and chemotherapy options are discussed. Large retrospective series show an association between surgical removal of the primary tumor or of lung metastases and improved long-term outcome in patients with oligometastatic disease. In the absence of data from prospective randomized studies, removal of the primary tumor or isolated metastatic lesions may be an attractive therapeutic strategy in this subset of patients, offering rapid disease control and potential for survival benefit. Some improvement in outcome may also be achieved with optimization of systemic therapies, possibly in combination with optimal local treatment.

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“…Data flow is shown in Figure 1 and study data is presented in Appendix 1. Two articles represented data from the same clinical trial Slamon et al, 2001), and three of the 71 abstracted articles were subsequently excluded because they used high-dose chemotherapy, which has limited application to current clinical practise (Lotz et al, 2005;Schmid et al, 2005;Kröger et al, 2006). The resulting 67 clinical trials represent 17 081 patients.…”

Section: Resultsmentioning

confidence: 99%

Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer

Sherrill

Amonkar

et al. 2008

Br J Cancer

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The relationship between overall survival (OS) and disease progression end points has been demonstrated in colorectal, colon, and non-small cell lung cancers. We assessed the association between OS and time-to-progression (TTP) or progression-free survival (PFS) in metastatic breast cancer (MBC) studies. A literature search retrieved all randomised controlled trials since 1994 in patients with MBC in which OS and either TTP or PFS were reported. Summary data on trial and patient characteristics were abstracted. Study effect sizes were derived as the ratio of median progression (or survival) times, which approximates the hazard ratio. Effects were centred at zero for regression analyses weighted by sample size. Numerous treatments were represented in 67 studies (17 081 patients). Modeling showed a positive association between outcomes for progression and survival (R 2 ¼ 0.30) with a slope of 0.32 (Po0.001) and a non-significant intercept. Thus, a treatment effect on TTP/PFS translated into a concordant effect on OS, but with attenuated effect size. Similar results were found in models of subsets and sensitivity analyses. These results demonstrate that treatment effects on progression end points in MBC trials are expected to result in treatment differences on OS that are smaller yet consistently in the same direction. British Journal of Cancer (2008) Most studies of anticancer agents are designed and powered to show differences between groups on disease progression end points such as response rates, time-to-progression, time-torecurrence or disease-free survival. Although increased survival time is clearly an implicit goal, it is difficult to establish in randomised studies when standard clinical practise is to change treatments at the onset of new progressive events. Especially in the metastatic setting, where expected survival time may be very short, the use of drug combinations or sequential use of multiple drug classes is commonplace. Increasingly, patients in clinical trials are offered alternate treatment upon progression. Consequently, few studies actually demonstrate an unequivocal survival benefit using intent-to-treat analysis approaches.In several tumour types, efforts have been made to justify the use of alternate, more easily established end points by showing how well they are correlated with survival. Several meta-analyses have been published (Table 1) that show a link between time-toprogression (TTP) or progression-free survival (PFS) with overall survival (OS) in metastatic colorectal or non-small cell lung cancer (Johnson et al, 2006) and colon cancer in the adjuvant setting (Sargent et al, 2005). For breast cancer, a moderately strong correlation between 2-year disease-free survival and 5-year overall survival was observed in the adjuvant setting (Ng et al, 2008). A meta-analysis of metastatic breast cancer studies found a positive relationship between objective response and overall survival on an individual patient basis, but the relationship was less clear when treatment regimens were compared...

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

Abstract: 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.

Cited by 11 publications

References 22 publications

Severe autologous GVHD after hematopoietic progenitor cell transplantation for multiple myeloma

Severe autologous GVHD after hematopoietic progenitor cell transplantation for multiple myeloma

International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured?

Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer

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