Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group.

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1-16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought.

Present treatment and future expectations in advanced pancreatic cancer.

Advanced or metastatic pancreatic cancer is an incurable disease. The main treatment is chemotherapy with cytotoxic agents. On the basis of our experience in clinical trials, the objectives have been to determine response rate, life prolongation and clinical benefit. In our trials and in those of other authors, all of these objectives have been met. Responses remain low; 5-25% of patients have a partial response, life prolongation is significantly achieved versus best supportive care, and clinical benefit is observed in 40-60% of patients. Rarely do patients survive for over 2 years and no patient is cured. The standard cytotoxic treatment is the agent gemcitabine. The addition of other agents, such as cisplatin, irinotecan, oxaliplatin and taxanes, in combination with gemcitabine, has shown higher response rates but overall survival has not significantly increased. Research related to monoclonal or gene therapies for pancreatic cancer has created hope. The horizon has been broadened by a recent report on a tyrosine kinase inhibitor, erlotinib (EGFR inhibitor) which has shown significantly longer median survival, when combined with gemcitabine versus gemcitabine alone. Other anti-angiogenic agents, such as cetuximab and the anti-Her-2, herceptin, are now being tested in ongoing trials. Farnesyl transferase inhibitors represent another direction which research is taking; this is related to the Ras-oncogenes (K-, H- and N-ras) which are known to be involved in signal transduction pathways regulating cell growth and differentiation in many human cancers including pancreatic. Trials of these and other targeting therapies have not produced the expected effectiveness. The combination of monoclonal and/or gene therapies with cytotoxic agents suggests there is hope for the future.

Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status.

INTRODUCTION: To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse. METHODS: The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR. RESULTS: The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007-0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51-101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97-12.84; P = 0.001) were independent predictive factors for CNS relapse. CONCLUSION: CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs.

Utilization of Systemic Chemotherapy in Advanced Urothelial Cancer: A Retrospective Collaborative Study by the Hellenic Genitourinary Cancer Group (HGUCG).

BACKGROUND: Advanced urothelial cancer (AUCa) is associated with poor long-term survival. Two major concerns are related to nonexposure to cisplatin-based chemotherapy and poor outcome after relapse. Our purpose was to record patterns of practice in AUCa in Greece, focusing on first-line treatment and management of relapsed disease. METHODS: Patients with AUCa treated from 2011 to 2013 were included in the analysis. Fitness for cisplatin was assessed by recently established criteria. RESULTS: Of 327 patients treated with first-line chemotherapy, 179 (55%) did not receive cisplatin. Criteria for unfitness for cisplatin were: Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2, 21%; creatinine clearance ≤ 60 mL/min, 55%; hearing impairment, 8%; neuropathy, 1%; and cardiac failure, 5%. Forty-six patients (27%) did not fulfill any criterion for unfitness for cisplatin. The main reasons for these deviations were comorbidities (28%) and advanced age (32%). Seventy-four (68%) of 109 patients who experienced a relapse received second-line chemotherapy. The most frequent reason for not offering second-line chemotherapy was poor PS or limited life expectancy (66%). CONCLUSION: In line with international data, approximately 50% of Greek patients with AUCa do not receive cisplatin-based chemotherapy, although 27% of them were suitable for such treatment. In addition, about one third of patients with relapse did not receive second-line chemotherapy because of poor PS or short life expectancy. Enforcing criteria for fitness for cisplatin and earlier diagnosis of relapse represent 2 targets for improvement in current treatment practice for AUCa.

Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients.

PURPOSE: To evaluate the predictive and prognostic value of peripheral blood cytokeratin-19 (CK-19) mRNA-positive cells in axillary lymph node-negative breast cancer patients. PATIENTS AND METHODS: Peripheral blood was obtained from 167 node-negative breast cancer patients before the initiation of any systemic adjuvant therapy, and was analyzed for the presence of CK-19 mRNA-positive cells using a real time polymerase chain reaction assay. The association with known prognostic factors and the effect of CK-19 mRNA-positive cells on patients' prognosis was investigated. RESULTS: CK-19 mRNA-positive cells were detected in the blood of 36 (21.6%) of the 167 patients. There was no correlation between the detection of CK-19 mRNA-positive cells in the peripheral blood and the various known pathologic and clinical prognostic factors; only overexpression of HER2 receptor (score 2+/3+) on the primary tumor was associated with a higher incidence of CK-19 mRNA-positive cell detection (P = .033). Multivariate analysis revealed that detection of peripheral blood CK-19 mRNA-positive cells was associated with early clinical relapse (P < .00001) and disease-related death (P = .008). CONCLUSION: Detection of peripheral-blood CK-19 mRNA-positive cells is an independent predictive and prognostic factor for reduced disease-free interval and overall survival, respectively, in node-negative breast cancer patients.