Current status of cediranib: the rapid development of a novel anti-angiogenic therapy.

Angiogenesis, the process whereby tumors develop new blood vessels to facilitate growth and metastasis, is a pivotal event in tumorigenesis. It is tightly regulated by the VEGF system. Cediranib (AZD2171, Recentin; AstraZeneca, London, UK) is a novel and potent small-molecule inhibitor of VEGF signaling, with activity against the three VEGF receptors, as well as other targets. This article provides a comprehensive and up-to-date synopsis of all pertinent preclinical and clinical studies detailing this promising new therapy.

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer.

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37-1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10-0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46-2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC.

Adjuvant treatment of breast cancer in postmenopausal women: role of exemestane.

Adjuvant hormonal therapy significantly reduces the risk of recurrence and death following surgery for estrogen receptor (ER)-positive early breast cancer. Previously, the gold standard hormonal therapy was tamoxifen, a selective modulator of the ER. However, large clinical trials conducted over the past decade have defined the efficacy of an alternative class of hormonal agent, namely the third-generation aromatase inhibitors (AIs): exemestane, letrozole, and anastrozole. On the basis of the pivotal International Exemestane Study (IES), exemestane, a steroidal third-generation AI, was licensed for the adjuvant treatment of postmenopausal women with ER-positive early breast cancer following 2-3 years of tamoxifen to complete a total of 5 years of adjuvant hormonal therapy. Here, we consider recent data to emerge primarily from the IES and Tamoxifen Exemestane Adjuvant Multicenter trials and consider their implications for the role of exemestane in the adjuvant treatment of breast cancer.

New approaches in the management of advanced breast cancer - role of combination treatment with liposomal doxorubicin.

Metastatic breast cancer (MBC) remains a major cause of morbidity and mortality in women worldwide. For three decades doxorubicin, alone or in combination with other cytotoxic agents, has been a mainstay of systemic therapy for MBC. However, its use is limited by cumulative cardiotoxicity. More recently liposomal formulations of doxorubicin have been developed which exhibit equal efficacy but reduced cardiotoxicity in comparison to conventional doxorubicin. The novel toxicity profile of liposomal doxorubicins has prompted their evaluation with various cytotoxic agents in patients with MBC. In addition, their favorable cardiac safety profile has prompted re-evaluation of concomitant therapy with doxorubicin and trastuzumab, a regimen of proven efficacy in MBC but previously considered to be associated with significant cardiotoxicity. We review clinical trial data addressing combination therapy with both pegylated and non-pegylated liposomal doxorubicin in patients with MBC.

Recombinant human epoetin beta in the treatment of chemotherapy-related anemia.

Anemia is a common complication of systemic anti-cancer treatment. In this context epoetin beta, like other erythropoiesis-stimulating agents (ESAs), has demonstrable efficacy in raising Hb concentration and reducing the requirement for red cell transfusion. Consequently ESA therapy has gained increasing prominence in the management of chemotherapy-related anemia. However, recent trial data have suggested a higher rate of thromboembolic events, enhanced tumor progression and reduced survival in some patients with cancer who receive ESA therapy. In response, regulatory authorities have mandated increasingly restrictive label changes. In light of these new developments we consider the current role of epoetin beta in the management of chemotherapy-related anemia.