triple therapy yields better results than standard of treatment for Stage IVs
 

ASCO 2009: ABSTRACT #1020: N0337: Phase II study of capecitabine in combination with vinorelbine and trastuzumab for the first or second treatment of HER2+ metastatic breast cancer [American Society of Clinical Oncology]
Background: Trastuzumab-containing regimes have dramatically improved outcome of patients with HER2+ breast cancer. Efforts to improve efficacy and tolerability of combination regimens with this monoclonal antibody are important for patient care. Thus, we conducted a multi-institutional phase II study of a triplet combination in patients eligible to receive either first- or second-line treatment for HER2+ metastatic breast cancer (MBC).
Methods: A phase II study designed to test that the true confirmed response rate (CRR) was at most 45% versus a true CRR of at least 65% was done (March 2005-June 2008). This design required that at least 25/45 confirmed responses in evaluable patients for the treatment to be considered promising. Patients received capecitabine 825 mg/m2 po (days 1-14), vinorelbine intravenously (IV) 25 mg/m2 days 1 and 8 every 3 weeks and trastuzumab IV 8mg/kg day 1, week 1, and then 6 mg/kg q 3 weeks. Tissue and blood have been collected for future studies on biomarkers.
Results: 47 women were accrued, one patient cancelled participation prior to receiving any study drug, and another had a major protocol violation. 45 patients were evaluable and 30 (67%) achieved a confirmed response, (26 patients, 58% had a confirmed partial response and 4 patients, 9% had a confrimed complete response). Median progression free survival was 11.3 months (95% CI 8.4-23.2 months), median overall survival was 27.2 months (95% CI: 26.6-NA months), and among the 30 responders, the median duration of response time was 15.5 months (95% 7.7-26.1 months). The most common grade 3 events include neutropenia 61%, fatigue 13%, skin reaction-hand-foot 11%, and leukopenia 11%. Alopecia was not noted with this regimen.
Conclusions: This triplet combination is effective, safe, and is promising in patients with HER2+ MBC. A phase III study should be conducted to compare the best doublet with this triplet combination whether this would lead to better clinical outcomes.

Any thought on whether this could work with someone who technically progressed on Capecitabine?

How funny, Rich...as I scrolled down to read your response, I was asking myself "I wonder if this combo would work for me..."
I progressed while on Navelbine + Herceptin, but wonder if adding Xeloda would bring NED around...?

I guess the question is whether the combo is additive or has synergy.

Jessica
I was thinking the same thing...i progressed on Xeloda, just wondering if it was added to the Navelbine I am on now it would work again....

The "triple therapy" idea has been around for many years.

For my raging mets I was put on a three-drug approach which included Herceptin and Navelbine mentioned in this study, with the addition of Taxol. (Capacitabine was still in development then.) I believe this was called "anti-microtubule" trial, with the addition of Herceptin for those of us HER2 positive.

These drugs did the trick for me. I took them on a weekly basis, and had red and white blood cell production support. It was a hard go, but worth it in the end. I happen to know that there are at least 2 of us still alive, and we both had Herceptin in addition to the other two drugs.

At the time, I was posting about this in 2003, most of the other members here said their docs did not support this type of chemo as it would impair "quality of life" too much. All these drugs were approved then and could have been given to anyone who wanted them.

Glad I bit the bullet and went ahead with that combo.

Yeah Steph,
You are certainly one of the success stories I come back to.
Capecitabine is known as antimetabolite..similar enough to Taxol?
For what it's worth, mom "progressed" on Xeloda in a couple of lung spots, not an overall kind of thing.
I wonder if the situation is heterogeneous, requiring blocking different pathways here and there. i.e. maybe the combo with Xeloda could work.

Thinking more about this since there seems to be steam behind the idea of cancer stem cells being ER-.
Still don't have answer on whther additive effects make it worthwhile even if Capecitabine alone didn't do the trick. Anyone else ask their oncs?

Rich,

Can you please provide a link to the literature discussing the hypothesis/research that cancer stem cells are ER-?

Thanks

Resistance to Endocrine Therapy: Are Breast Cancer Stem Cells the Culprits? Ciara S. O’Brien1, Sacha J. Howell1, Gillian Farnie1 and Robert B. Clarke1 http://www.springerlink.com/content/...35/contact.gif
(1) Breast Biology Group, School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK
http://www.springerlink.com/content/...35/contact.gif Robert B. Clarke
Email: robert.clarke@manchester.ac.uk Received: 16 December 2008 Accepted: 10 February 2009 Published online: 28 February 2009
Abstract From a developmental point of view, tumors can be seen as aberrant versions of their tissue of origin. For example, tumors often partially retain differentiation markers of their tissue of origin and there is evidence that they contain cancer stem cells (CSCs) that drive tumorigenesis. In this review, we summarise current evidence that breast CSCs may partly explain endocrine resistance in breast cancer. In normal breast, the stem cells are known to possess a basal phenotype and to be mainly ERα−. If the hierarchy in breast cancer reflects this, the breast CSC may be endocrine resistant because it expresses very little ERα and can only respond to treatment by virtue of paracrine influences of neighboring, differentiated ERα+ tumor cells. Normal breast epithelial stem cells are highly dependent on the EGFR and other growth factor receptors and it may be that the observed increased growth factor receptor expression in endocrine-resistant breast cancers reflects an increased proportion of CSCs selected by endocrine therapies. There is evidence from a number of studies that breast CSCs are ERα− and EGFR+/HER2+, which would support this view. CSCs also express mesenchymal genes which are suppressed by ERα expression, further indicating the mutual exclusion between ERα+ cells and the CSCs. As we learn more about CSCs, differentiation and the expression and functional activity of the ERα in these cells in diverse breast tumor sub-types, it is hoped that our understanding will lead to new modalities to overcome the problem of endocrine resistance in the clinic.

Full article:
http://www.springerlink.com/content/.../fulltext.html