Evolving Approaches to Metastatic Breast Cancer Previously Treated with Anthracycline

[Rich66]

1: Clin Breast Cancer. 2009 Jun 1;9:S58-S65.Links

Evolving Approaches to Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes.

Murphy CG, Seidman AD.
Department of Breast Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
Despite major advances in the adjuvant treatment of breast cancer, many women will develop metastatic disease, either de novo or following optimal adjuvant therapy. Further effective therapeutic options are needed for women who progress following anthracycline- and taxane-containing regimens. Capecitabine is approved by the US Food and Drug Administration as monotherapy in this setting. Other agents such as gemcitabine or vinorelbine might be considered based on multiple phase II studies. Combination therapies generally increase response rates but with a concomitant increase in toxicity. Other agents that have been studied in this setting include etoposide, irinotecan, and pemetrexed. Novel agents undergoing testing include the fluorinated vinca alkaloid vinflunine and the halichondrin B analogue eribulin. Responses have been seen in taxane-pretreated patients with the use of another conventional taxane, novel formulations, or alternative schedules. Pegylated liposomal doxorubicin might be considered in some patients for whom there is a concern regarding cardiac toxicity with the conventional preparation. The epothilones are a novel group of microtubule-stabilizing agents. Ixabepilone is a member of this class that has been approved as monotherapy in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine. It is also approved with capecitabine in patients whose cancer is resistant to treatment with anthracyclines and taxanes. Decision-making regarding treatment selection must take into account multiple patient and tumor factors. The therapeutic indices of the available treatments should be considered in the context of the individual patient.

[Rich66]

1: Eur J Cancer. 2009 Jul 15. [Epub ahead of print] Links

The clinical efficacy of cytotoxic agents in locally advanced or metastatic breast cancer patients pretreated with an anthracycline and a taxane: A systematic review.

Jassem J, Carroll C, Ward SE, Simpson E, Hind D.
Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland.
INTRODUCTION: Currently available evidence does not provide definitive guidance regarding the optimal chemotherapy agents and combinations in anthracycline- and taxane-pretreated advanced breast cancer. We performed a systematic review of controlled clinical trials of the cytotoxic agents currently used for this population in Europe: capecitabine, gemcitabine, vinorelbine, docetaxel, paclitaxel and paclitaxel protein-bound particles. METHOD: A systematic review of randomised (RCT) and non-randomised controlled clinical trials (non-RCTs). The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS); secondary outcomes were duration of response (DR), overall response rate (ORR), adverse events and quality of life (QoL). Six electronic databases and grey literature sources were searched; reference tracking was performed on included publications. A narrative synthesis was conducted: heterogeneity of study design and interventions prevented meta-analysis. RESULTS: No randomised controlled trial (RCT) found any significant differences between any of the regimens in terms of OS. In terms of PFS, only gemcitabine plus vinorelbine performed significantly better than its comparator, vinorelbine alone. For secondary outcomes, only capecitabine plus bevacizumab had a significantly better outcome than its comparator, capecitabine alone, in terms of ORR. A low quality non-RCT found that both capecitabine monotherapy and a combination of capecitabine plus vinorelbine were significantly more effective than vinorelbine alone in terms of OS and ORR. Across all trials, median OS for these patients typically remained less than 16 months. CONCLUSION: The quantity and quality of the available evidence regarding the efficacy of the particular chemotherapy regimens in patients with advanced breast cancer pretreated with an anthracycline and a taxane is extremely limited. New effective therapies are sorely needed in this population.