Efficacy of biological agents in metastatic triple-negative breast cancer.

Metastatic triple-negative breast cancer (mTNBC) represents 15% of invasive breast cancers. Prognosis is poor, and there is no specific target therapy but biological agents combined with chemotherapy may be effective. To assess the role of biological agents in metastatic triple-negative breast cancer we performed a systematic review of phase III randomized controlled trials published from January 2006 to February 2013 and presentations at ESMO, ASCO, and SABCS congresses in 2010-2012. We consulted PubMed and ClinicalTrials.gov. Only studies comparing biological agents and chemotherapy versus chemotherapy alone were considered. Relevant statistical variables were log of the hazard ratio and relative variance for progression-free survival (PFS) and overall survival (OS). Of 353 PubMed publications and 229 studies registered on ClinicalTrials.gov, 10 trials were selected and 5293 patients were analyzed: 1546 had mTNBC. Biological agents considered were bevacizumab, sunitinib, sorafenib, lapatinib, iniparib and cetuximab. In addition, a meta analysis of the four studies containing bevacizumab was performed and it showed a PFS improvement with a relative risk reduction of 35% (95% CI: 25-43%). No effect on OS was observed. No PFS and OS benefit was detected with the other agents. No improvement of OS was detected in patients treated with biological agents plus chemotherapy, while a significant PFS improvement was observed only for bevacizumab and cetuximab. The overall impact of these agents on patient survival was not as great as expected, probably because the molecular basis of this illness needs to be better understood so that treatment can be more appropriately tailored.

Safe chemotherapy and hormone therapy for treating early breast cancer in a glucose 6-phosphate dehydrogenase-deficient patient: case report.

Breast cancer is the leading cause of neoplasia-related deaths among women, but no data are available in the literature on the safe use of oncological treatments in glucose 6-phosphate dehydrogenase (G6PD)-deficient patients. This case report describes, for the first time, the treatment of a G6PD-deficient woman diagnosed with breast cancer who underwent adjuvant treatment after quadrantectomy and axillary node dissection. After conservative surgery, many patients require adjuvant treatment with hormone therapy (HT) and/or chemotherapy. Anthracyclines are considered a cornerstone in this setting but, because of their oxidative properties, are contraindicated in G6PD-deficient patients. Despite the absence of data in the literature on their use in G6PD-deficient patients, we chose to use docetaxel and cyclophosphamide because these agents were not predicted to elicit oxidative stress. The patient completed six cycles of docetaxel and cyclophosphamide chemotherapy, and no adverse reactions were observed. Tamoxifen was excluded as a HT as a nonoxidative agent was required; therefore, an aromatase inhibitor was used as adjuvant therapy. Considering the high frequency of breast cancer and G6PD deficiency worldwide, there are little data available in the literature on the oxidative properties of oncological drugs. The oncological community must report cases in which patients with hereditary enzymatic deficiencies are treated successfully with anticancer agents. This would enable clinicians to have access to data that would be very useful in the choice of a safe treatment program.

A mono-institutional prospective study on the effectiveness of a specialist psychotherapeutic intervention (POI) started at the diagnosis of cancer.

PURPOSE: We evaluated the effectiveness of an early POI in newly diagnosed cancer patients in reducing the occurrence of psychiatric disturbances. METHODS: We designed a mono-institutional prospective study involving all new patients admitted to the Oncology Department of Fatebenefratelli and Ophtalmic Hospital in Milan from January 2005 until September 2008. During the first visit, the oncologist could offer support with a psycho-oncologist. The patients who accepted had a first interview (T0), during which they took a self-evaluation test (HADS, Hospital Anxiety and Depression scale). On the basis of the score, the psycho-oncologist could offer psychotherapy and/or pharmacological intervention, if necessary. At the end of the eight sessions (T1), the patient repeated the self-evaluation test with the HADS, and we analysed both the difference in the HADS score between T0 and T1 and the clinical evaluation of the psycho-oncologist. RESULTS: Three hundred eighteen patients were evaluated with a psychoanalytical psychotherapy approach by two psycho-oncologists through a first interview and 90 of them were eligible for the present study also for the evaluation of HADS. The average HADS score in T0 was 15.26 for depression (sd=3.21) and 13.86 for anxiety (sd = 2.05). The reassessment at the end of the psychotherapy (T1) showed an average HADS score of 5.94 for depression (sd = 3.11) and 6.58 for anxiety (sd = 2.88). Only five patients were treated with a pharmacological approach alone. CONCLUSIONS: Considering all the limits of our study, we may conclude that an early POI significantly reduces patients' psychiatric symptoms and the risk of a negative evolution of pathological situations in those patients who are motivated and express a need for psychological help.

Maintenance or consolidation therapy in small-cell lung cancer: a systematic review and meta-analysis.

OBJECTIVE: To assess the role of maintenance or consolidation therapy in the treatment of small-cell lung cancer (SCLC), a meta-analysis of all published randomized clinical trials (RCTs) was performed in order to provide an overall meta-analysis and indirectly compare the effect of chemotherapy, interferons, and other biologic agents. METHODS: Electronic databases were searched for publication reporting of RCTs comparing maintenance or consolidation therapy versus placebo or follow-up alone until December 2008. Hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), with their relative 95% confidence intervals (CI), were derived. In the calculation of HRs, the "no maintenance" arm served as a reference. The a priori value of p<0.05 was chosen as significant level for statistical tests. RESULTS: Twenty-one RCTs, encompassing 3,688 patients, were eligible for the present analysis: 11 RCTs employing chemotherapy, 6 interferons (4 alpha and 2 gamma), and 4 other biological agents. Overall, no statistical advantage in OS (HR 0.93, 95% CI 0.87-1.00; p = 0.05) or in PFS (HR 0.98, 95% CI 0.91-1.06; p = 0.63) was reported for maintenance or consolidation therapy. Statistical evidence of different effects among the four types of therapy was detected for OS (χ(2) test for heterogeneity: 8.07 [3 df]; p = 0.04), but not for PFS. A statistically significant reduction of mortality was detected in those studies assessing the efficacy of chemotherapy (HR 0.89, 95% CI 0.81-0.98; p = 0.02) and of interferon-alpha (HR 0.78, 95% CI 0.64-0.96; p = 0.02). CONCLUSIONS: The maintenance or the consolidation approach failed to improve the outcomes of SCLC. A survival advantage is suggested for maintenance chemotherapy and interferon-alpha, but its clinical impact needs to be confirmed by further studies.

Biological and clinical features in predicting efficacy of epidermal growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), developed for patients with advanced non-small cell lung cancer (NSCLC), give modest results similar to those with chemotherapy. There is evidence of a greater survival benefit from TKIs in patients with certain molecular and clinical features, but results are conflicting. To assess the role of these factors in predicting TKI efficacy, a pooled analysis was performed on data from randomized trials in NSCLC. MATERIALS AND METHODS: An electronic search of all randomized trials comparing the efficacy or activity of TKIs and a pooled analysis were performed. The hazard ratio (HR) with 95% confidence interval (CI) was calculated for each level of the factors and an interaction test was used to detect differences in treatment effect related to the different levels. RESULTS: Of ten randomized trials identified, five were considered for analysis. Smoking was shown to be the only clinical factor to have a predictive effect (non smokers: overall survival (OS) HR 0.53, 95% CI 0.42-0.67; smokers: HR 0.91, 95% CI 0.81-1.02; p-value for interaction <0.001). A negative predictive value was suggested for K-ras mutations (K-ras(+): HR 1.97 95% CI 1.16-3.33; K-ras(-): HR 0.79, 95% CI 0.59-1.05; p-value for interaction 0.003). CONCLUSION: At the present time, none of the biological features which have been evaluated in patients who have undergone therapy using TKIs is proven to be of predictive value; only K-ras mutations and smoking habits can be considered as a possible criteria for selection. Results of prospective randomized trials on biological markers are awaited.

Osteonecrosis of the jaw (ONJ) in cancer patients treated with Bisphosphonates: how the knowledge of a phenomenon can change its evolution.

GOALS OF THE WORK: Osteonecrosis of the jaw (ONJ) is a severe complication of bisphosphonates treatment. Bisphosphonates reduce skeletal adverse events and give a clinical benefit to cancer patients. Therefore, it is necessary to identify appropriate procedures to reduce ONJ injures by using a successful monitoring program. In a retrospective study we analyzed the impact of a prevention program based on clinical oral cavity examination, dentists, and patients' education. The aim of the study was to evaluate if this approach might improve ONJ outcome in patients receiving pamidronate or zoledronate. MATERIALS AND METHODS: We analyzed retrospectively two different groups of patients treated at our Institution: patients treated from October 2003 to June 2005 (group A) and patients treated from June 2005 to April 2007 (group B). In June 2005 the prevention program started for all our patients. MAIN RESULTS: One hundred and eighty-six cancer patients with bone involvement, treated with bisphosphonates, were considered. Sixteen of them developed ONJ: eight before and eight after June 2005. We observed a consistent difference in the evolution of the two groups. In the first group, four patients underwent a major surgery (one partial maxillectomy, complicated by septic shock and oronasal communication; two partial mandibulectomies; and one segmental mandibular resection), with an important impairment of their quality of life; while the eight new ONJ cases, diagnosed after June 2005, were successfully treated without aggressive dental interventions, and achieved a good control of symptoms. CONCLUSIONS: Bisphosphonates-related ONJ is a frequent adverse event (8.6%). The monitoring program proved very efficient to improve the clinical outcome of ONJ, avoiding an aggressive treatment and using a conservative approach and medical therapy.

An oxaliplatin + 5-fluorouracil bolus + folinic acid (BFOL) regimen as first-line treatment in metastatic colorectal cancer patients.

AIMS AND BACKGROUND: The purpose of the study was to evaluate the outcome of metastatic colorectal cancer patients treated, as first line, with 5-fluorouracil bolus/leucovorin + oxaliplatin, in terms of response, progression-free and overall survival. MATERIALS AND METHODS: A retrospective cohort of consecutive metastatic colorectal cancer patients, treated from 2003 to 2006, was identified and analyzed. All patients, without a central venous device, were treated with oxaliplatin + 5-fluorouracil and leucovorin. RESULTS: Twenty-five metastatic colorectal cancer patients were treated. No 3-4 grade toxicity was observed. Five of 23 patients achieved a partial response: one of them resulted in a complete response after radiofrequency and another one after surgery. Fifteen of 23 patients had stable disease (one underwent radical surgery after chemotherapy, obtaining a complete remission) and 3 had progressive disease. Median progression-free survival was 7.2 months, and median overall survival was 30 months. CONCLUSIONS: Based on this case-series study, the regimen seems to offer a good control of disease (86.9%) and can be considered as an alternative choice for patients who cannot receive continuous infusion.