Long-term outcome of neoadjuvant endocrine therapy with aromatase inhibitors in elderly women with hormone receptor-positive breast cancer.

BACKGROUND: Aromatase inhibitors (AIs) are more effective than tamoxifen as neoadjuvant endocrine therapy (NET) for hormone receptor (HR)-positive breast cancer. Here we report the surgical and long-term outcome of elderly postmenopausal patients with locally advanced, HR-positive breast cancer treated with preoperative AIs. METHODS: Between January 2003 and December 2012, 144 postmenopausal patients inoperable with breast conservative surgery (BCS) received letrozole, anastrozole, or exemestane as NET. Patients underwent breast surgery and received adjuvant AIs. Adjuvant systemic therapy, chemotherapy and/or trastuzumab, and adjuvant radiotherapy were administered as appropriate, but limited to high-risk patients with few or no comorbidities. RESULTS: After a median follow-up of 49 months, 4 (3.0 %) patients had local relapse, 18 (12.5 %) had distant metastases, and 24 (17.0 %) died. BCS was performed in 121 (84.0 %) patients. A tumor size <3 cm and human epidermal growth factor receptor 2 (HER2) negativity were predictors of BCS. The achievement of BCS and grade G1 were significantly associated with longer disease-free survival (DFS) (p = 0.009 and p = 0.01, respectively) and overall survival (p = 0.002 and p = 0.005, respectively). Residual tumor ≤2 cm (yT0-yT1) in the longest diameter after NET was also statistically associated with longer DFS (p = 0.005). CONCLUSIONS: The results of this retrospective study indicate that elderly breast cancer patients with a tumor size <3 cm at diagnosis and HER2 negativity have a higher probability of achieving BCS after NET. Moreover, patients treated with BCS and with grade G1 tumor have a reduced risk of recurrence and death in the long-term follow-up.

Effectiveness and response predictive factors of erlotinib in a non-small cell lung cancer unselected European population previously treated: a retrospective, observational, multicentric study.

AIMS AND BACKGROUND: Erlotinib approval was supported by the positive results of a large multicentric phase III trial (BR.21 study) that included 10% Asiatic patients and the remaining were North-American Caucasian. It is well-known that the efficacy of tyrosine kinase inhibitors is strongly influenced by ethnicity and other genetic factors. It is, therefore, relevant to establish whether the same profile of efficacy is seen in an unselected population and whether the results of BR.21 can be generalized to other patient populations, such as that described here. METHODS: In this retrospective, observational, multicentric study, we assessed effectiveness and potentially response predictive factors in 222 unselected Italian patients, with stage IIIB/IV non-small-cell lung cancer, with performance status from 0 to 3, who had received at least one line of chemotherapy, treated with the standard dose of erlotinib (150 mg once daily) until disease progression or unacceptable toxicity. RESULTS: The disease control rate was 60.9% (135 patients). Median progression-free survival and overall survival times were 3.1 months and 7.97 months, respectively. The characteristics of non-smoker, female gender, performance status 0 or 1 were associated with a significantly better prognosis in terms of disease control rate and were also predictive of longer overall survival and progression-free survival. The 1-year survival rate was 38.79%. Even though Italian patients baseline characteristics were strongly different to those reported in pivotal BR.21 trial in terms of age, performance status, line treatment and ethnic group, our study confirms the favorable effectiveness profile in real clinical practice of erlotinib according to results from the pivotal study BR.21. CONCLUSIONS: Today, we know that epidermal growth factor receptor (EGFR) status assessment is mandatory before starting first-line therapy and that the presence of only certain clinical characteristics initially associated with sensitivity to EGFR-tyrosine kinase inhibitors, as reported in this study, is not sufficient in selecting patients candidates to such treatments.

Rare diseases in Italy: analysis of the costs and pharmacotherapy.

Purpose of this research was to analyse the rare diseases drug supply paths in the Italian region of Campania (Health District 47 of the Local Medical Company Naples 1), with a particular focus on current regulations in this field, and quantify the economic incidence of such pathologies in each quarter of 2007 and 2008. Rare, or orphan, diseases are especially serious and onerous from every point of view. Patients meet significant difficulties in obtaining information and in identifying the most appropriate treatment path within the health care system. Pharmaceutical prescriptions were analysed in order to identify the number of patients for each pathology in each quarter of the years 2007 and 2008, the drugs used, the quantity of each drug, and the costs for treatments. Data show a significant increase of costs during each quarter of the year 2008, as well as from 2007 to 2008. In the absence of specific guidelines for the Campania Region, the Local Medical Company of Naples 1 has established a procedure for patients affected by rare diseases that enables them to receive at no cost products that otherwise would not be distributed for free by the health care system.

The impact of a pharmacist as a member of healthcare team on facilitating evidenced-based prescribing of innovative drugs in an Italian oncology department.

AIMS AND BACKGROUND: At the Oncology Department of the Chieti and Ortona Hospitals, the pharmacist designated by the Abruzzo Region to oversee the obligatory monitoring of innovative oncological drugs listed in the database of the Italian Medicines Agency (AIFA) collaborates with oncologists to educate them about evidenced-based prescribing for off-label uses of drugs and to optimize the efficiency of spontaneous reporting of adverse drug reaction (ADR) local system. METHODS: The contribution of the pharmacist as a member of the healthcare team was evaluated using the following indices: the percentage of off-label prescriptions of the innovative drugs monitored, the number of reported ADRs, and the percentage of pharmacist suggestions actually implemented by physicians. RESULTS: In the course of 3 years (2008-2010), the pharmacist monitored a total of 843 patients treated with 716 appropriate uses and 127 off-label uses of drugs, oversaw a reduction in the latter from 28.3% in 2008 to 9.6% in 2010, and contributed to almost tripling the number of reported ADRs, from 10 in 2008 to 27 in 2010. In 2010, the pharmacist identified 60 potentially inappropriate prescribing cases, and proposed more appropriate prescriptions for each case: 68.3% (41) of the suggestions were implemented by the physicians and only 31.7% (19) were not. According to answers to a questionnaire administered at the end of the 2010 to evaluate the usefulness of this particular collaboration, physicians are interested in continuous and extensive collaboration. CONCLUSIONS: This article demonstrates that a pharmacist, active in the department as part of the heath-care team, can facilitate evidenced-based prescribing for off-label uses of drugs and improve spontaneous reporting of ADRs.

Gemcitabine-induced posterior reversible encephalopathy syndrome: a case report.

Gemcitabine is a commonly used chemotherapeutic agent for a variety of tumors. Although this nucleoside analog antineoplastic agent is similar in structure to cytarabine, central nervous system toxicities have rarely been attributed to gemcitabine. The posterior reversible encephalopathy syndrome (PRES) is a condition characterized by reversible neurological and radiological findings that has been associated with use of chemotherapeutic and more recently novel targeted therapies. We describe one case of a 41-year-old woman with PRES under treatment for leiomyosarcoma because of the probable association with gemcitabine. Our case, to our knowledge, represents the seventh published report of this particular toxicity. Naranjo algorithm, efficacious method for assessing the causality of adverse drug reactions (ADRs) from a case report, suggests a direct casual relationship. PRES is probably a rare complication of gemcitabine, but the oncologist should take it into careful consideration, because PRES is reversible with treatment of current hypertension or removal of the causative agent. However, failure to quickly recognize the syndrome and discontinue the offending agent may result in profound and permanent central nervous system dysfunction or death.

Role of Hydroxamate-Based Histone Deacetylase Inhibitors (Hb-HDACIs) in the Treatment of Solid Malignancies.

Hydroxamate-based histone deacetylase inhibitors (Hb-HDACIs), such as vorinostat, belinostat and panobinostat, have been previously shown to have a wide range of activity in hematologic malignancies such as cutaneous T-cell lymphoma and multiple myeloma. Recent data show that they synergize with a variety of cytotoxic and molecular targeted agents in many different solid tumors, including breast, prostate, pancreatic, lung and ovarian cancer. Hb-HDACIs have a quite good toxicity profile and are now being tested in phase I and II clinical trials in solid tumors with promising results in selected neoplasms, such as hepatocarcinoma. This review will focus on their clinical activity and safety in patients with advanced solid neoplasms.

Long-term outcome of neoadjuvant systemic therapy for locally advanced breast cancer in routine clinical practice.

PURPOSE: The aim of this study is to evaluate the long-term outcome of patients with locally advanced breast cancer treated with neoadjuvant systemic chemotherapy (NST) in routine clinical practice. METHODS: Four hundred and nine patients were identified between January 1999 and December 2011. All patients received NST followed by surgery, adjuvant treatments and radiotherapy, as appropriate. RESULTS: At Kaplan-Meier analysis, patients with surgical stage III disease were more likely to develop distant metastasis and die from breast cancer (p < 0.001). Luminal A and luminal B/HER2-negative patients had better prognosis; moreover, patients with hormone receptor (HR)-positive tumors had a significantly longer DRFS (p < 0.0049) and OS (p < 0.0001) compared with patients with HR-negative tumors as well as patients who underwent breast-conserving surgery (DRFS and OS: p < 0.001). In multivariate analysis, HR negativity (p < 0.001 for both DRFS and OS), mastectomy (DRFS: p = 0.009; OS: p = 0.05) and stage III disease (DRFS: p < 0.001; OS: p = 0.003) were associated with shorter DRFS and OS. CONCLUSIONS: HR negativity, mastectomy and pathological stage III disease are the variables independently associated with a worse outcome in our cohort of patients. These data are of high interest since they derive from a very heterogeneous group of patients, treated with different neoadjuvant/adjuvant regimens outside of clinical trials and with a long follow-up period.