Chemotherapy with or without estrogenic recruitment in metastatic breast cancer. A randomized trial of the Gruppo Oncologico Nord Ovest (GONO)

Conte, Pierfranco; Baldini, Editta; Gardin, G.; Pronzato, P.; Amadori, Dino; Carnino, F; Monzeglio, C; Gentilini, Patrizia; Gallotti, Pietro; Micheli, Rita De; Venturini, M.; Rubagotti, Alessandra; Rosso, Riccardo

doi:10.1093/oxfordjournals.annonc.a010637

Cited by 14 publications

(2 citation statements)

References 11 publications

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“…Forty-two percent (31/73) anthracycline and 30 percent (11/37) taxane publications did not provide a detailed description of how the progression-based endpoint was determined: of these publications 6 anthracycline and no taxane trial arm pairs reported PFS data for which scrutiny of the methods and results did not reveal obvious deviations from the U.S. FDA definition of PFS. (11;17;18;24;45;61) The majority of these publications (4/6) were published in 1990 or earlier. These six trials were excluded in a sensitivity analysis of trials meeting the “strict” definition of PFS.…”

Section: Resultsmentioning

confidence: 99%

Progression-free survival as a surrogate endpoint in advanced breast cancer

Miksad

Zietemann

Gothe

et al. 2008

Int J Technol Assess Health Care

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Objectives Progression-free survival (PFS) has not been validated as a surrogate endpoint for overall survival (OS) for anthracycline (A) and taxane-based (T) chemotherapy in advanced breast cancer (ABC). Using trial-level, meta-analytic approaches, we evaluated PFS as a surrogate endpoint. Methods A literature review identified randomized, controlled A and T trials for ABC. Progression-based endpoints were classified by prospective definitions. Treatment effects were derived as hazard ratios for PFS (HRPFS) and OS (HROS). Kappa statistic assessed overall agreement. A fixed-effects regression model was used to predict HROS from observed HRPFS. Cross-validation was performed. Sensitivity and subgroup analyses were performed for PFS definition, year of last patient recruitment, line of treatment, and constant rate assumption. Results Sixteen A and fifteen T trials met inclusion criteria, producing seventeen A (n = 4,323) and seventeen T (n = 5,893) trial-arm pairs. Agreement (kappa statistic) between the direction of HROS and HRPFS was 0.71 for A (p = .0029) and 0.75 for T (p = .0028). While HRPFS was a statistically significant predictor of HROS for both A (p = .0019) and T (p = .012), the explained variances were 0.49 (A) and 0.35 (T). In cross-validation, 97 percent of the 95 percent prediction intervals crossed the equivalence line, and the direction of predicted HROS agreed with observed HROS in 82 percent (A) and 76 percent (T). Results were robust in sensitivity and subgroup analyses. Conclusions This meta-analysis suggests that the trial-level treatment effect on PFS is significantly associated with the trial-level treatment effect on OS. However, prediction of OS based on PFS is surrounded with uncertainty.

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Section: Resultsmentioning

confidence: 99%

Progression-free survival as a surrogate endpoint in advanced breast cancer

Miksad

Zietemann

Gothe

et al. 2008

Int J Technol Assess Health Care

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“…Despite oxygen being a critical factor in the regulation of proliferation and survival, it is unclear whether other factors may initiate quiescence in solid tumors prior to oxygen becoming limiting (15,20,21). To date stimulating tumor cell proliferation for therapeutic gain using strategies that focus on single factors has largely been unsuccessful and it might be that identifying more than one factor will be required (22)(23)(24). Tumor-derived quiescence is likely due to the interrelation of many diffusible factors, an issue that is compounded by the difficulty of independently studying diffusion limitations of molecules supplied by the blood and those released from cells (25).…”

Section: Introductionmentioning

confidence: 99%

Targeting Quiescent Tumor Cells via Oxygen and IGF-I Supplementation

Kyle¹,

Baker²,

Minchinton³

2012

Cancer Research

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Conventional chemotherapy targets proliferating cancer cells, but most cells in solid tumors are not in a proliferative state. Thus, strategies to enable conventional chemotherapy to target noncycling cells may greatly increase tumor responsiveness. In this study, we used a 3-dimensional tissue culture system to assay diffusible factors that can limit proliferation in the context of the tumor microenvironment, with the goal of identifying targets to heighten proliferative capacity in this setting. We found that supraphysiologic levels of insulin or insulin-like growth factor I (IGF-I) in combination with oxygen supplementation were sufficient to initiate proliferation of quiescence cells in this system. At maximal induction with IGF-I, net tissue proliferation increased 3-to 4-fold in the system such that chemotherapy could trigger a 3-to 6-fold increase in cytotoxicity, compared with control conditions. These effects were confirmed in vivo in colon cancer xenograft models with demonstrations that IGF-I receptor stimulation was sufficient to generate a 45% increase in tumor cell proliferation, along with a 25% to 50% increase in chemotherapy-induced tumor growth delay. Although oxygen was a dominant factor limiting in vitro tumor cell proliferation, we found that oxygen supplementation via pure oxygen breathing at 1 or 2 atmospheres pressure (mimicking hyperbaric therapy) did not decrease hypoxia in the tumor xenograft mouse model and was insufficient to increase tumor proliferation. Thus, our findings pointed to IGF-I receptor stimulation as a rational strategy to successfully increase tumor responsiveness to cytotoxic chemotherapy.

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Survival of metastatic breast carcinoma patients over a 20‐year period

Gennari

Conte

Rosso³

et al. 2005

Cancer

247

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The distribution of subvertical grooves on interproximal wear dental facets from the El Sidrón (Asturias, Spain) Neandertals is described and analyzed. Out of 93 teeth, 64.5% present subvertical grooves, including a high frequency (50%) on the anterior dentition. Contrary to some studies, subvertical grooves from adjacent facets perfectly overlap each other and do not interdigitate, probably forming small channels. Both the facet and the groove surface share the same polished appearance, suggesting a common origin. Statistical analyses reveal that the number of grooves is neither dependent on the degree of occlusal wear, nor on the position on the tooth or the individual's age. However, facet width is an important factor determining the number of subvertical grooves. The etiology of subvertical grooves formation on Neandertal teeth remains unclear. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.

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Chemotherapy with or without estrogenic recruitment in metastatic breast cancer. A randomized trial of the Gruppo Oncologico Nord Ovest (GONO)

Cited by 14 publications

References 11 publications

Progression-free survival as a surrogate endpoint in advanced breast cancer

Progression-free survival as a surrogate endpoint in advanced breast cancer

Targeting Quiescent Tumor Cells via Oxygen and IGF-I Supplementation

Survival of metastatic breast carcinoma patients over a 20‐year period

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