Treatment of metastatic breast cancer: state-of-the-art, subtypes and perspectives.

Current treatment of metastatic breast cancer (MBC) aims at achieving meaningful clinical responses, improved quality of life, long-term remissions, prolonged survival, and dares to hope for a cure in a small percentage of cases. This article will discuss both consensus and controversies in the management of MBC in the context of the new evolving breast cancer molecular classification. Hormonal therapy remains the mainstay of management of MBC Luminal A and B.

Safety and pharmacokinetics of sorafenib combined with capecitabine in patients with advanced solid tumors: results of a phase 1 trial.

Sorafenib (twice daily [bid]) plus capecitabine (2 weeks on schedule/1 week off schedule) safety and pharmacokinetics were investigated in patients with advanced solid tumors (N = 35). Cohort 1 (n = 13) included sorafenib 200 mg bid and capecitabine 1050 mg/m(2) bid; cohort 2 (n = 4), sorafenib 400 mg bid and capecitabine 1050 mg/m(2) bid; cohort 3 (n = 6), sorafenib 200 mg bid and capecitabine 1050 mg/m(2) bid (cycles 1 and 2), then 400 mg bid and capecitabine 1050 mg/m(2) bid (cycle 3 onwards); and cohort 4 (n = 12), sorafenib 400 mg bid and capecitabine 850 mg/m(2) bid. The combination of sorafenib and capecitabine was generally well tolerated.

The use of chemotherapy regimens carrying a moderate or high risk of febrile neutropenia and the corresponding management of febrile neutropenia: an expert survey in breast cancer and non-Hodgkin's lymphoma.

Background: The use of chemotherapy regimens with moderate or high risk of febrile neutropenia (defined as having a FN incidence of 10% or more) and the respective incidence and clinical management of FN in breast cancer and NHL has not been studied in Belgium. The existence of a medical need for G-CSF primary and secondary prophylaxis with these regimens was investigated in a real-life setting.

Methods: Nine oncologists and six hematologists from different Belgian general hospitals and university centers were surveyed to collect expert opinion and real-life data (year 2007) on the use of chemotherapy regimens with moderate or high risk of febrile neutropenia and the clinical management of FN in patients aged <65 years with breast cancer or NHL.

Prevention and management of major side effects of targeted agents in breast cancer.

Targeted therapies have evolved dramatically over the last few years. The heterogeneity of breast cancer is now understood on a molecular level, and different targeted therapeutic strategies have been approved in an attempt to tailor treatment strategies. Although the incidence of side effects is expected to be low due to target specificity, this is not always the case.

Is VEGF a predictive biomarker to anti-angiogenic therapy?

Tumor growth and metastasis are dependent on angiogenesis. Inhibiting angiogenesis has therapeutic potentials for treating cancer. Researchers have identified many of the pathways involved in angiogenesis and proposed selective targeted strategies.

A phase 1 study of BMS-275183, a novel oral analogue of paclitaxel given on a daily schedule to patients with advanced malignancies.

Purpose: BMS-275183 is an oral C-4 methyl carbonate analogue of paclitaxel that has the same mechanism of action, stabilization of tubulin polymerization. The present study was designed to: (i) assess the safety and tolerability of BMS-275183, and (ii) determine a suitable Phase II dose of BMS-275183 when given on a continuous daily schedule to patients with advanced solid tumor(s).

Methods: This was a multi-institutional, open-label, Phase I, single-arm dose escalation study in which cohorts of eligible patients with advanced malignancies were treated with BMS-275183 orally on a continuous daily schedule.

Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine.

Purpose: The activity and safety of eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, were evaluated in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, taxane, and capecitabine.

Patients And Methods: Eligible patients in this single-arm, open-label phase II study received eribulin mesylate (1.4 mg/m(2)) administered as a 2- to 5-minute intravenous infusion on days 1 and 8 of a 21-day cycle.

Febrile neutropenia: a critical review of the initial management.

The present state of the art for management of patients with febrile neutropenia has been reviewed as well as potential ways to improve it in the future. A major advance has been the possibility to predict, accurately and early, the risk of complications and death in those patients. While the algorithm for therapy in low-risk patients is presently straightforward, significant progresses are needed for patients who are at higher risk of presenting severe complications.

Molecular targeted therapy in prevalent tumors: learning from the past and future perspectives.

Important advances have been achieved with molecular targeted agents in clinical oncology. Breast, colon, and lung cancer, are now commonly treated with a combination of chemotherapy and targeted agents. In this article the authors discuss the limitations of targeted therapy development, failures of previous studies, and possible strategies for an intelligent drug development.

Management of metastatic HER2-positive breast cancer progression after adjuvant trastuzumab therapy - current evidence and future trends.

Trastuzumab is now considered the standard of care for the adjuvant treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients, yet a sizable number of HER2-positive patients do not benefit from this treatment. For patients who progress on or after completion of adjuvant trastuzumab therapy, the standard of care is uncertain. Newer tyrosine kinase inhibitors and monoclonal antibodies are being evaluated in clinical trials for optimisation of treatment in this group.

Prevention of febrile neutropenia in chemotherapy-treated cancer patients: Pegylated versus standard myeloid colony stimulating factors. Do we have a choice?

The pertinent literature on clinical studies comparing the respective value of myeloid colony stimulating factors to pegfilgrastim as a prevention of febrile neutropenia in chemotherapy-treated cancer patients has been reviewed. Pegfilgrastim is definitely not inferior to filgrastim or other myeloid colony stimulating agents with respect to duration of grade IV neutropenia and delivery of full chemotherapy dose on time; several comparative studies indicate a trend to less frequent febrile neutropenia with pegfilgrastim.

AACR-NCI-EORTC International Conference 2009.

The AACR-NCI-EORTC international conference held on 15-19 November 2009 in Boston (MA, USA) was a unique opportunity to discuss basic and translational research and the therapeutic implications in relation to molecular targets in cancer. The conference was divided into plenary and educational sessions, keynote presentations, special lectures, proffered papers and poster sessions. This conference is a joint effort of prestigious organizations (EORTC, NCI and AACR) that have been involved for several years in basic and clinical cancer research.

Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer.

Purpose: Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer-those with and those without prior trastuzumab treatment-in an open-label, multicenter, phase II trial.

Patients And Methods: Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily.

Is tailored adjuvant treatment for colon cancer possible?

High-risk stage II and stage III colon cancers are associated with significant recurrence rates after surgical resection. Adjuvant chemotherapy has demonstrated a significant disease-free and overall survival benefit for patients, even if not helpful for all. Currently, there are limited clinical and molecular markers that can predict response to chemotherapy and clinical outcome in advanced colon cancer.

Changing the clinical picture of challenging tumors: tales becoming reality?

The treatment of neoplastic diseases has become increasingly dependent on tumor biology and is focused on targeted therapy. Understanding complex networks of intracellular signaling pathways, blockades of specific targets and a myriad of other approaches has brought new fuel to the battle against many types of cancer. Unfortunately, the degree of benefit achieved in this new era of cancer treatment has not been distributed homogeneously among the different disease types.

Management of head and neck cancer in elderly patients.

Head and neck cancer (HNC) represents a heterogeneous group of tumours requiring multimodality approaches. It is debatable whether HNC treatment in geriatric patients should be different to that delivered for younger patients. Furthermore, the risk of death seems to be higher in HNC patients with higher co-morbidity status.

Larotaxel: broadening the road with new taxanes.

Significant advances in cancer treatment have been achieved with novel targeted and state-of-the-art treatments. While the targeted treatments have received much attention in recent years, the more 'traditional' chemotherapeutic agents continue to play an important role in several malignancies. Former taxanes such as docetaxel and paclitaxel, with their broad anticancer activity, have contributed significantly to the improved treatment of a number of neoplastic diseases.

Evaluation of the prognostic significance of serum galectin-3 in American Joint Committee on Cancer stage III and stage IV melanoma patients.

Galectin-3 (Gal-3) is a member of the beta-galactoside-binding lectins family and has been implicated in angiogenesis, tumor invasion, and metastatic process in vitro and in vivo. As we showed recently that advanced melanoma patients presented high serum level of Gal-3, we investigated the association of this protein with the outcome of melanoma patients. Whether this protein could be a biomarker has not been assessed, and we compared the prognostic value of serum Gal-3 in multivariate analysis with lactate dehydrogenase, C-reactive protein and S100B.

Should the indications for the use of myeloid growth factors for the prevention of febrile neutropenia in cancer patients be extended?

Purpose Of Review: Prevention of infectious complications of chemotherapy-induced granulocytopenia is a major issue in preventive medicine, as febrile neutropenia is still associated with an overall 10% mortality and extensive morbidity and cost.

Recent Findings: The prescription of granulocyte colony-stimulating factors should not be determined according to a risk prediction of febrile neutropenia considering solely type of chemotherapy and according to cost-effectiveness; other factors appear now to be important for making the decision, namely age and the presence of various comorbid factors.

Summary: It is likely that the consideration of these newly recognized risk factors and the availability of more affordable granulocyte colony-stimulating factors will lead, in the near future, to an extension of the presently recognized indications for the prescription of granulocyte colony-stimulating factors.

Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study.

Background: Inflammatory breast cancer is an aggressive and biologically distinct form with a higher frequency of HER2 overexpression than other breast cancers. For patients with resistance to conventional anthracycline or taxane and trastuzumab treatment, options are limited. Lapatinib, an oral reversible inhibitor of epidermal growth factor receptor tyrosine kinases, previously had a 50% response rate in a cohort of 30 patients with HER2-overexpressing (HER2+) recurrent or anthracycline-refractory inflammatory breast cancer.

Concomitant chemo-radiotherapy as standard therapy in limited-stage small-cell oesophageal cancer: a summary of 3 clinical cases and review of the literature.

Small-cell carcinoma of the oesophagus (SCCO) is a rare and aggressive malignant tumour associated with a poor prognosis. Between 1994 and 2002, three patients with SCCO were treated in our institution, representing 1.96% (3 out of 153) of all oesophageal malignancies seen during this period.

Hypoxia-inducible factor in cancer angiogenesis: structure, regulation and clinical perspectives.

Tumor hypoxia is a common feature of many cancers. A master regulator of hypoxic response is the transcription factor hypoxia-inducible factor-1 (HIF-1). It functions as a master regulator of oxygen and undergoes conformational changes in response to varying oxygen concentrations.

Pemetrexed combined with paclitaxel: a dose-finding study evaluating three schedules in solid tumors.

The objectives of this phase I study were to determine the maximum tolerated dose (MTD), recommended phase II dose (RD), antitumor activity, safety, and pharmacokinetics of pemetrexed-paclitaxel combination. Patients (N = 95) with advanced solid tumors were assigned to three schedules (21-day cycles [q21d]). Starting doses for each schedule of pemetrexed and paclitaxel, respectively, were: (S1) 400 and 135 mg/m(2) on d1; (S2) 400 mg/m(2) d1 and 40 mg/m(2) d1 and d8; S3) 400 mg/m(2) d8 and 30 mg/m(2) d1 and d8.