Multidisciplinary evaluation at baseline and during treatment improves the rate of compliance and efficacy of deferasirox in elderly myelodysplastic patients.

BACKGROUND: Deferasirox (DFX) is used to reduce iron levels in patients with myelodysplastic syndrome (MDS) who develop iron overload after chronic red blood cell infusions. However, DFX can be associated with renal and gastrointestinal toxicities, which may cause treatment interruption or discontinuation. This study aimed to determine the effectiveness and safety of DFX in patients with MDS. METHODS: This multicenter, retrospective, observational study was conducted at two hospitals in Italy. Elderly patients with transfusion-dependent MDS received DFX for up to 12 months and were divided into two groups: group A comprised patients who were not under multidisciplinary assessment; group B comprised patients under multidisciplinary control. Treatment effectiveness was estimated by monitoring the serum ferritin (SF) levels throughout the study. Any treatment-related adverse events (AEs), clinically relevant analytical alterations, and reasons for treatment discontinuation were monitored. RESULTS: The study included 44 patients (13 female, 31 male; median age 77.0 years). At 3 months, SF levels decreased by ≥20 % in 29 and 31 % of patients in groups A and B, respectively, in 17 and 36 % of patients at 6 months, and in 22 and 58 % at 12 months. The most common AEs were diarrhea and increased serum creatinine, which were more frequent in group A. The discontinuation rate after renal AE was 15 and 5 % in groups A and B, respectively. CONCLUSION: Multidisciplinary evaluation can be an effective strategy for monitoring renal function in patients on DFX therapy, to improve treatment adherence and overall efficacy in elderly patients with MDS.

Is soluble mesothelin-related protein an upfront predictive marker of pleural mesothelioma? A prospective study on Italian workers exposed to asbestos.

OBJECTIVE: Soluble mesothelin-related peptide (SMRP) may be useful in the diagnosis and detection of early stage mesothelioma. We investigated the SMRP upfront predictive role for mesothelioma in asbestos-exposed workers. METHODS: A total of 1,715 subjects underwent a first visit and were invited for a follow-up after 1 and 2 years, with a clinical examination and blood sampling. SMRP was measured by an ELISA assay. RESULTS: Median SMRP at the first visit was 0.45 [interquartile range (IQR) i.e. 25th-75th percentile: 0.30-0.67 nmol/l]. In all, 1,676 subjects (97.8%) were followed up for a median period of 47.1 months. SMRP was measured at the first visit and at both follow-up visits in 1,536 subjects. At follow-up, 3 subjects were diagnosed with an epithelioid mesothelioma. In these cases, SMRP at the first visit ranged from 0.17 to 0.52 nmol/l. Malignant pleural mesothelioma was diagnosed 9-17 months after the last SMRP evaluation. No SMRP variation was observed during the follow-up. Other 61 miscellaneous cancers were diagnosed (median SMRP at first visit: 0.50 nmol/l, IQR: 0.34-0.71 nmol/l). CONCLUSIONS: Our results did not support the usefulness of SMRP as an early marker for the detection of the disease for a time interval of 1 year.

Safety of First-line Chemotherapy with Metronomic Single-agent Oral Vinorelbine in Elderly Patients with NSCLC.

BACKGROUND/AIM: The optimal therapeutic use of metronomic vinorelbine has not yet been defined. We aimed to assess the safety of metronomic oral vinorelbine in first-line treatment of elderly patients with advanced lung cancer who were unfit for polychemotherapy. Progression-free survival, response rate and overall survival were secondary end-points. PATIENTS AND METHODS: Seventy-six patients received 50 mg of oral vinorelbine three times per week, until disease progression, patient refusal or unacceptable toxicity. Patients were evaluated for response and toxicity after one cycle of chemotherapy. The treatment was considered feasible with a grade 3/4 toxicity rate lower than 20%. RESULTS: Clinical benefit was observed in 50% of patients. Median overall survival was 8.0 months. Grade 1/2 toxicity was observed in 53 patients (69.7%), grade 3 toxicity in eight patients (10.5%). One patient had grade 4 diarrhea. CONCLUSION: Metronomic oral vinorelbine is safe in elderly patients, allowing for long-term disease stabilization with optimal patient compliance.

Clinical Features and Treatment Outcome of Malignant Pleural Mesothelioma.

BACKGROUND: Malignant pleural mesothelioma is a problematic condition due to poor prognosis and difficulties in management. We evaluated the treatment and outcome of 378 mesothelioma patients referred to 6 Italian Oncology Departments. METHODS: Demographic and clinical data were collected. Treatment was assessed in terms of chemotherapy (line of treatment, pemetrexed-based regimen, other therapies), surgery, and radiotherapy. Response to therapy, progression-free survival, and overall survival were evaluated. RESULTS: 36 and 342 patients received best supportive care and active treatment, respectively; 86 patients underwent surgery, and 26 received trimodal therapy. Disease control after first-line chemotherapy was achieved in 74.2% of patients (75.7% in patients treated with pemetrexed combined with other drugs and 69% with pemetrexed as monotherapy). The disease control rate was 82.6% in pemetrexed re-challenged individuals. Median survival time was 11.6 months with supportive care, 16.2 months with chemotherapy only, 32.4 months with surgery plus chemotherapy, and 47.2 months with trimodal therapy. A more favorable prognosis was observed in responders to first-line therapy who were then actively treated with second-line (24.8 vs. 11.8 months in non-responders, p < 0.001) and third-line chemotherapy (28.9 vs. 17.8 months in non-responders, p = 0.005). CONCLUSION: Mesothelioma patients benefited from chemotherapy alone only when retreated in the second line after response to first-line therapy.

Cardiovascular adverse events complicating the administration of rituximab: report of two cases.

Rituximab is a murine/human chimeric monoclonal antibody directed against the CD20 antigen. It is widely used in combination with polychemotherapy regimens for the treatment of hematological disorders. There is no evidence of direct cardiotoxicity of the drug but a few cases of cardiovascular adverse events have been reported in the literature. We report on two patients affected by stage IV non-Hodgkin lymphoma with bone marrow infiltration and peripheral blood involvement who experienced cardiovascular accidents temporally related to rituximab infusion. In both cases the monoclonal antibody was administered in association with a polychemotherapy regimen but administration was postponed several days later in order to avoid severe cytokine release syndrome because of the high tumor burden. The first case concerns an episode of atrial fibrillation in a patient with a diagnosis of small B-cell lymphoma. The episode happened immediately after rituximab infusion. In the second case there was an episode of chest pain associated with fever and chills during rituximab infusion in a patient with a diagnosis of mantle cell lymphoma. In both cases we noticed an unusual correlation between symptom recurrence and the speed of rituximab infusion. Both patients presented several cardiovascular risk factors but preliminary cardiac function assessment excluded signs of heart dysfunction. The pathogenesis of cardiovascular events during rituximab infusion remains unclear. A key role might be played by cytokine release from B cells as a consequence of rituximab activity. Moreover, pre-existing silent cardiac damage could be co-responsible for the clinical manifestations we reported. We consider our clinical experience relevant because it raises an issue of good clinical practice: despite rituximab's good tolerability profile, patients with cardiovascular risk factors should undergo accurate cardiac assessment so that silent heart disease can be detected. If the suspicion of cardiac damage is high, more extensive cardiac assessment is recommended.

Individual predictors of increased serum mesothelin in asbestos-exposed workers.

The soluble mesothelin-related peptide (SMRP), a candidate marker for screening of subjects with asbestos exposure, is influenced by some individual and clinical factors. The aim of this study was to quantify the role of age, smoking, weight, presence of diseases and exposure to asbestos on serum SMRP levels in a large series of subjects exposed to asbestos, possible candidates for mesothelioma screening. One thousand seven hundred and four participants underwent clinical examination and were interviewed on medical anamnesis, occupation, smoking and weight. SMRP was measured by an ELISA assay. Overall, median SMRP was 0.4 (IQR 25-75: 0.3-0.7) nmol/l. It was higher in current smokers and in subjects with a cumulative asbestos exposure >50 ff/cc/years than in all the other subjects (p < 0.001 and p = 0.002, respectively). SMRP was positively correlated with age (ρ = 0.11, p < 0.001) and, inversely, with BMI (ρ = -0.15, p < 0.001). SMRP was lower in healthy subjects (n = 1,217: median 0.4 nmol/l) than in subjects with malignant tumors (n = 118: 0.5 nmol/l; p = 0.01), asbestos-related pleural lesions (plaques or thickenings, n = 152: 0.6 nmol/l; p < 0.001) and other benign diseases (n = 182: 0.5 nmol/l; p = 0.04). Multivariate analysis revealed significant predictors of increased SMRP: age >57 years, current smoking, a positive anamnesis for cancer and for asbestos-related pleural lesions, and BMI < 25. Some clinical and demographic variables are associated with serum SMRP levels. The degree of these associations is low, nevertheless they should be accounted for in the interpretation of SMPR as a candidate marker predictive of mesothelioma. The potential predictive value of serum SMRP in screening/surveillance programs must be validated in prospective studies.

Weekly standard doses of rh-EPO are highly effective for the treatment of anemic patients with low-intermediate 1 risk myelodysplastic syndromes.

For more than 20 years erythropoietin (rHEPO) has largely been used to treat anemia in myelodysplastic syndromes (MDS). Early clinical trials showed erythroid responses in no more than 15-25% of patients. In the last decade, a better selection of MDS patients suitable for a therapeutic challenge with rHEPO, alone or in combination with G-CSF, allowed for an increased response-rate, averaging around 40%. More recently, an even higher percentage of responses have been obtained using higher-doses of rHEPO (up to 80,000 IU/weekly) in lower-risk MDS patients. This treatment however, especially at such high doses, is costly and not easily affordable for prolonged periods. The aim of this study was to verify if the use of "standard" doses of rHEPO could induce a satisfying response-rate with a less expensive treatment schedule in IPSS-defined "lower-risk" MDS anemic patients. From January 2005 to December 2009 a total of 55 consecutive anemic (Hb ≤ 10 g/dL) patients (29 males, 26 females, median age 78 years) with low-intermediate-1 risk MDS were treated after informed consent with rHEPO (40,000 IU once a week subcutaneously) for at least 3 months; at the end of this period, erythroid response was assessed, and responders were allowed to continue the treatment indefinitely, whereas non-responders were considered "off study". Both efficacy and safety of the treatment were recorded and evaluated. After 3 months of treatment, 36 out of 55 (65.5%) patients achieved an erythroid response to rHEPO according to IWG 2006 criteria. Higher response-rates to rHEPO were related with both lower IPSS and particularly WPSS scores. Treatment was safe, and only 1 patient had to discontinue the treatment because of unmanageable side-effects. Among the 36 responders, 28 (77%) maintained the response after a median follow-up of 46 months. Our data indicate that standard doses of rHEPO are at least as effective as higher-doses for correcting anemia in lower-risk MDS patients; in this clinical scenario, this schedule allows for a consistent reduction of costs without precluding the achievement of a durable erythroid response.