E. Pozzi

Which patients with metastatic breast cancer benefit from subsequent lines of treatment? An update for clinicians.

The outcome of patients with metastatic breast cancer (MBC) has clearly improved over the past decades and the proportion of women living with their disease for several years is increasing. However, the usefulness of multiple lines of treatment is still debated and under evaluation. The available data from both randomized trials and large retrospective series are reviewed and discussed in order to analyze management practices, with emphasis on potential prognostic and predictive factors for clinical outcome. At present, evidence-based medicine provides some support for the use of second-line and to a lesser degree and in selected cases, third-line chemotherapy in human epidermal growth factor receptor 2 (HER2) negative MBC. Beyond third-line treatment, messages from recently reported retrospective studies also suggest a clear potential gain for women receiving further therapies after disease progression, since each line can contribute to a longer survival. In HER2-positive disease, the data from observational and retrospective studies support a clinical benefit from the use of trastuzumab beyond disease progression and emerging evidences from randomized controlled trials are leading to the introduction of newer HER2-targeted therapies in multiple lines. The question ‘How many lines of treatment should we give patients?’ clearly needs further research through prospective, high-quality clinical trials, aiming for a better definition of factors with prognostic and predictive role. In the meantime, the ‘optimal’ treatment strategy should probably be to use as many therapeutic options as possible, either in sequence or combination, to keep the best efficacy/toxicity balance, considering MBC as a chronic disease.

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life

Background A prospective, multicenter trial was undertaken to assess the activity, safety, and quality of life of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer (MBC). Patients and methods Fifty-two women with HER2-negative MBC who were candidates for second-line chemotherapy for the metastatic disease were enrolled and treated at three centers in Northern Italy. All patients had previously received taxane-based chemotherapy in the adjuvant or first-line metastatic setting. Single-agent nab-paclitaxel was given at the dose of 260 mg/m2 as a 30-minute intravenous infusion on day 1 each treatment cycle, which lasted 3 weeks, in the outpatient setting. No steroid or antihistamine premedication was provided. Treatment was stopped for documented disease progression, unacceptable toxicity, or patient refusal. Results All of the enrolled patients were evaluable for the study endpoints. The objective response rate was 48% (95% CI, 31.5%–61.3%) and included complete responses from 13.5%. Disease stabilization was obtained in 19 patients and lasted >6 months in 15 of them; the overall clinical benefit rate was 77%. The median time to response was 70 days (range 52–86 days). The median progression-free survival time was 8.9 months (95% CI, 8.0–11.6 months, range 5–21+ months). The median overall survival point has not yet been reached. Toxicities were expected and manageable with good patient compliance and preserved quality of life in patients given long-term treatment. Conclusion Our results showed that single-agent nab-paclitaxel 260 mg/m2 every 3 weeks is an effective and well tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC patients, and that it produced interesting values of objective response rate and progression-free survival without the concern of significant toxicity. Specifically, the present study shows that such a regimen is a valid therapeutic option for that ‘difficult to treat’ patient population represented by women who at the time of disease relapse have already received the most active agents in the adjuvant and/or metastatic setting (ie, conventional taxanes).

Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization

Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

Vinflunine in Advanced Transitional Cell Cancer of the Urothelial Tract: A Potential Option for Maintenance Therapy? A Case Series

Introduction: Vinflunine is a microtubule inhibitor approved in Europe as second-line treatment of advanced transitional cell cancer of the urothelium (TCCU). The inability to continue with a first-line platinum-based regimen beyond 6 cycles suggested investigating the use of vinflunine as switch maintenance therapy in patients with response or stable disease after first-line therapy. Methods: Patients with advanced TCCU and documented disease control after 3-6 cycles of first-line platinum-based chemotherapy received vinflunine maintenance therapy within 6 weeks of the last cycle. Our analysis aimed to examine the performance of vinflunine in terms of activity and safety in such a patient population. Results: 28 consecutive patients were studied. After a median follow-up of 25 months, vinflunine was associated with a median progression-free survival of 9 months (range 4 to > 16 months) and a disease control rate of 64%; median overall survival was not reached. Treatment was well tolerated, with no unexpected safety events. The most common adverse events of grade ≥ 3 were neutropenia (21%) and constipation (14%); no toxicity-related death occurred. Conclusions: Our results suggest that vinflunine may be a suitable maintenance treatment option for TCCU patients who received a maximum of 6 cycles of platinum-based chemotherapy commonly used as first-line treatment.

Analisi retrospettiva della prevalenza di complicanze correlate alle procedure di chemioembolizzazione intra-arteriosa epatica (TACE) nelle differenti classi di rischio

Transcatheter hepatic chemoembolization (TACE) is widely used in the treatment of unresectable hepatic tumors. Although considered relatively safe, TACE has been associated with several complications. The aim of this study was to determine the prevalence of complications and correlate them with some know risk factors. Between 2004 and 2009 we treated 155 patients (106 men and 49 women) with 297 sessions of TACE. 193 patients had primitive liver tumor and 104 had metastases from different primitivities. The patients were aged 49–86 years. TACE procedures were performed either with drug loaded microspheres (136 sessions with DCBead®; 124 with Hepasphere®) and with iodized oil (33 with Lipiodol®). The chemoterapeutic agent used was Epidoxorubicin in 217 sessions, Irinotecan in 30 and Oxaliplatin in 50. Our data showed that major complications occurred in 16.5% of patients. Specifically we found acute pancreatitis (2.7%), liver abscess (3%), cholecystistis (3.7%) and autoimmune thrombocytopenia (3.4%). Around 80 % of patients had postembolization syndrome that is not considered a complication but rather an expected outcome of embolotherapy. Complications occurred more frequently in diabetic than in non diabetic patients (26.7% vs 13.1%; p=0.006). Conversely we didn’t find any statistically significant differences according to the embolization agents used (Lipiodol® vs microspheres), the chemotherapic agent (Epidoxorubin vs Oxalplatin vs Irinotecan ), the age of the patients and the histology (primary vs metastatic tumors). All patients received antibiotic therapies before and after TACE; no statistically significant differences were found among the different classes of antibiotics used. Also no more complications were found with combined therapies (TACE+RFTA) than with TACE alone. Among the know risk factors only diabetes increases the prevalence of complications of TACE. TACE with Lipiodol® is more painful than drug loaded microspheres.