Metronomic Chemotherapy in Triple-Negative Metastatic Breast Cancer: The Future Is Now?

Triple-negative breast cancer (TNBC) shows a very bad prognosis, even in early stages of disease. Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. In the present article, we review preclinical and clinical data of metronomic administration of chemotherapy agents with or without biological agents in TNBC cell lines and patients, contextually reporting data from the VICTOR-2 study in the subgroup of patients with TNBC, in order to stimulate new ideas for the design of clinical trials in this subset of patients.

Metronomic chemotherapy with oral vinorelbine (mVNR) and capecitabine (mCAPE) in advanced HER2-negative breast cancer patients: is it a way to optimize disease control? Final results of the VICTOR-2 study.

PURPOSE: The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients. The VICTOR-2 study was designed to confirm these results. METHODS: Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day, continuously. The primary endpoint was the clinical benefit rate (CBR); secondary endpoints were toxicity, objective response rate (ORR), and progression-free survival (PFS). RESULTS: Eighty patients were evaluable for the primary efficacy analysis. Median age was 65.3 years; most patients had HR-positive tumors (65 %). The CBR was 45.7 % (95 % CI 28.8-63.4) and 51.1 % (95 % CI 35.8-66.3) in first- and ≥ second-line therapy, respectively. The ORR was 35.5 % in first-line (95 % CI 19.2-54.6) and 25.6 % in ≥second-line (95 % CI 13.5-41.2). The median duration of response was 11.3 and 6.4 months and PFS rates at 1 year were 24.3 and 22.2 %, respectively. In triple-negative breast cancer patients (N = 28, 35 %) a lower, but clinically relevant CBR (35.7, 95 % CI 18.6-55.9) was observed. The main toxicities per cycle were non-febrile neutropenia (1.1 %), hand-foot syndrome (1.0 %), nausea and vomiting (1.0 %), leucopenia (0.8 %), fatigue (0.7 %), and diarrhea (0.4 %). CONCLUSION: The VICTOR-2 study confirms the clinical activity of mVNR and mCAPE in HER2-negative breast cancer patients, suggesting that the easy schedule of administration, which requires monthly blood tests and limits patients' dependence on hospitals, and the low cost of the drugs are valuable elements, even for countries with limited access to innovative or expensive drugs.

[Quality assessment of health promotion web sites]. / Analisi della qualità dei siti web riguardanti la promozione della salute.

The continuous expansion of the use of Internet has determined an increase in the number of web sites, including those related to health promotion. Even if this new tool provides a faster way to find the desired information, the high number of different sites can confuse the user especially when they present inconsistent data. For this reason, according to the principles contained in the Minerva Manual, we have built a template to evaluate the quality of health care related web sites, and we have verified its validity applying it to ten different sites. The results of this analysis show that the attention to the requirements varies according to the target users, the site focus and the sponsoring agency. Finally we have proposed an ideal web site, choosing, for each requirement in the evaluation grid, the approach that we considered best among the ones adopted by the ten examined sites.

Candidosis in the intensive care unit: a 20-year survey.

Deep-seated candidosis is a major problem in critically ill patients. Colonization with candida has been identified as an important independent risk factor for the development of candidaemia. Since the 1980s routine surveillance cultures have been performed on patients admitted for six or more days to the 'E. Vecla' intensive care unit (ICU) of the IRCCS Ospedale Maggiore di Milano. Colonization was observed on admission to the ICU in 59 of 117 (50%) patients in 2000 and 10 others developed colonization during their stay on the unit. A similar colonization rate was found in a survey performed 16 years earlier. The incidence of non-albicans Candida species, however, increased in 2000. In particular, 24 patients were culture positive for Candida glabrata at some point during their hospital stay, whereas this species was isolated from only one patient in 1983-1984. Antifungal susceptibility testing performed by Sensititre Yeast One revealed no resistance among 19 C. albicans strains tested. In contrast, fluconazole resistance was observed in two of 39 (5%) C. glabrata isolates from 23 patients. In the period 1983-2002, 28 candida bloodstream infections were identified and 12 were considered to be ICU-acquired (2.6/1000 hospitalized patients; 0.33/1000 patient days). The low rate of ICU-acquired candidaemia despite the inclusion of severely compromised patients in this study confirms the usefulness of routine mycological surveillance in preventing deep-seated candidosis.

Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study.

In order to update the epidemiological and mycological profile of candidaemia in Europe, the European Confederation of Medical Mycology conducted a prospective, sequential, hospital population-based study from September 1997 to December 1999. A total of 2,089 cases were documented by 106 institutions in seven European countries. Rates of candidaemia ranging from 0.20 to 0.38 per 1,000 admissions were reported. Candida albicans was identified in 56% of cases. Non-albicans Candida species were most frequently isolated from patients with haematological malignancies (65%). With increasing age, an increasing incidence of Candida glabrata was seen. The 30-day mortality rate was 37.9%. The survey results underline the burden of candidaemia in a wide range of patient populations, confirm the importance of non- albicans species, and provide baseline data for future surveillance studies at a European level.

European Confederation of Medical Mycology (ECMM) prospective survey of candidaemia: report from one Italian region.

An ECMM epidemiological prospective survey of candidaemia was performed in one Italian region (Lombardy; population: 8 924 870) by the National Society of Medical Mycology (FIMUA) from September 1997 to December 1999. In total, 569 episodes were reported with an overall rate of 0.38/1000 admissions, 4.4/100000 patient days. Predisposing factors included presence of an intravascular catheter (89%), antibiotic treatment (88%), surgery (56%), intensive care (45%), solid tumour (28%), steroid treatment (15%), haematological malignancy (7%), HIV infection (6%), fetal immaturity (4%). Mucous membrane colonization preceded candidaemia in 83% of patients. Candida albicans was identified in 58% of cases, followed by Candida parapsilosis (15%), Candida glabrata (13%), Candida tropicalis (6%). Septic shock occurred in 95 patients. Crude mortality was 35%, the highest in C. tropicalis fungaemia (44%), the elderly (64%) and solid tumour cancer patients (43%). Intravascular catheter removal was associated with higher survival rate (71 vs. 47%). This survey underscores the importance of candidaemia in hospital settings.