Final results of the real-life observational VICTOR-6 study on metronomic chemotherapy in elderly metastatic breast cancer (MBC) patients.

Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT's activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75-98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3-4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.

Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study.

PURPOSE: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. METHODS: We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). RESULTS: Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9-7.2) and 12.1 months (95% CI: 9.6-16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0-18.4), 6.1 months (95% CI: 4.0-8.9) for CTX-based and 5.3 months (95% CI: 4.1-9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3-16.7 and CTX-based ones (95%CI: 8.7-52.8). Tumour response, PFS and OS decreased proportionally in later lines. CONCLUSION: This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Metronomic chemotherapy for advanced breast cancer patients in the real world practice: Final results of the VICTOR-6 study.

Metronomic chemotherapy (mCHT) 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. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

[186Re]HEDP in the palliation of painful bone metastases from cancers other than prostate and breast.

AIM: Palliative therapy using [186Re]hydroxyethylidene diphosphonate (HEDP) has been widely tested in patients with bone metastases from prostate and breast cancers. Whereas, to the best of our knowledge, only few cases of bone metastases from tumors other than prostate and breast treated with [186Re]HEDP have been reported. The aim of this paper is to report our experience with 186Re-HEDP in the palliation of painful bone metastases from tumors other than prostate and breast. METHODS: In this study 41 patients (17 non-small cell lung cancer-NSCLC, 1 small cell lung cancer, 1 lung neuroendocrine tumor, 8 bladder cancer, 3 kidney cancer, 3 gastric cancer, 1 uterine carcinoma, 1 colon cancer, 1 rhinopharynx carcinoma, 1 medullary thyroid carcinoma, 1 ovarian cancer, 1 esophagus cancer, 2 carcinoma of unknown origin) are evaluated. All patients had lesions with increased [99mTc]MDP uptake and none had radiological findings of mainly osteolytic lesions. A total of 46 therapeutic cycles were performed using a [186Re]HEDP activity of 1 295 MBq for each administration. After treatment, patients were followed up for 3 months or to the time of pain recurrence (if longer than 3 months). Responses were evaluated using a validated method considering the modifications of pain index, analgesic intake and performance status. RESULTS: Treatment efficacy was complete in 49% (20/41) of patients, partial in 36% (15/41) and negative in 15% (6/41). Namely, we observed 35% (6/17) complete, 41% (7/17) partial and 24% (4/17) negative responses in patients with NSCLC and 63% (5/8) complete, 25% (2/8) partial and 12% (1/8) negative responses in patients affected by bladder cancer. The median duration of pain relief in responder patients was 10 weeks. A mild platelet toxicity occurred in 32% (13/41) of patients. CONCLUSIONS: Pain palliation with [186Re]HEDP seems highly effective and safe also in patients with bone metastases from cancers other than prostate and breast. Patients who can benefit from the treatment with [186Re]HEDP can be selected on the basis of [99mTc]MDP bone scan and radiological examination findings.

Ipsilateral supraclavicular lymph nodes metastases from breast cancer as only site of disseminated disease. Chemotherapy alone vs. induction chemotherapy to radical radiation therapy.

BACKGROUND: To define the role of radiotherapy (RT) in the treatment of ipsilateral supraclavicular lymph-nodes metastases (ISLM) from breast cancer as only site of disseminated disease, we started a prospective non-randomized clinical trial in 1989. Here we report the final results with a median follow-up of 8.75 years. PATIENTS AND METHODS: Thirty-seven patients (pts), with ISLM from breast cancer, were consecutively enrolled into two arms. Arm A (18 pts): chemotherapy (CT) for six courses. Arm B (19 pts): CT for three courses followed by RT to the site of ISLM at 'radical' dose of 50-60 Gy. RESULTS: In arm A, a median Time to Progression (TtP) of 7 months with a median Overall Survival (OS) of 28 months was recorded. In comparison, patients in arm B had a longer median TtP with 20 months as well as a better median OS with 41 months, respectively. An actuarial five-year disease-free survival of 5.5% was obtained in arm A vs. 21% in arm B. A statistically significant difference in TtP was demonstrated between the two groups (P = 0.01). CONCLUSIONS: These data demonstrate that a better event-free survival could be achieved in patients with ISLM submitted to induction CT and radical irradiation. This also translated into a longer survival although this did not achieve statistical significance. We want to stress the importance of local control by RT since it does imply that not all of these patients have micrometastases at the time of relapse in the supraclavicular fossa.

[Acute myocardial infarction complicated by ventricular aneurysm during pregnancy. A clinical case and review of the literature]. / Infarto acuto del miocardio complicato da sviluppo di aneurisma ventriculare in gravidanza. Descrizione di un caso e revisione della letteratura.

Acute myocardial infarction is an uncommon complication in pregnant women. The case of a 30-years-old patient who suffered of an acute myocardial infarction during the first trimester of pregnancy, with secondary development of left ventricular aneurysm is presented. She had a sudden death 3 months after delivery, while waiting for coronary arteriography.

Cisapride and dexamethasone in the prevention of delayed emesis after cisplatin administration.

Management of delayed emesis (DE) remains unsatisfactory, and only 50% of the patients achieve complete protection. Cisapride is a strong prokinetic gastrointestinal drug that could have a role in the prevention of DE. We enrolled 31 adult naive outpatients who were scheduled to receive cisplatin chemotherapy at doses of > or = 75 mg/m2. All patients received the same prophylactic treatment for acute emesis (20 mg dexamethasone and 8 mg ondansetron i.v.) and, as preventive therapy for DE, oral cisapride, 10 mg every 8 h on days 2-4, combined with dexamethasone i.m., 8 mg twice daily on days 2 and 3, and 4 mg twice daily on day 4. All patients were evaluable for activity. Complete protection from acute vomiting was 80.7%, from nausea 71% and from nausea/vomiting 64.5%. The overall protection from DE (days 2-4) was 74.1% for vomiting, 64.5% for nausea and 58% for nausea/vomiting. In our study the combination of cisapride and dexamethasone was effective, giving 58% of complete protection from DE, and it is therefore worthy of further studies.

Oxaliplatin and raltitrexed in the treatment of inoperable malignant pleural mesothelioma: results of a pilot study.

AIMS AND BACKGROUND: The treatment of inoperable malignant pleural mesothelioma is a challenge for the oncologist. Available chemotherapy regimens achieve poor results, therefore new agents or combinations are needed. In a phase I study, the combination of oxaliplatin and raltitrexed was shown to be active against malignant pleural mesothelioma. We herein report the results of a pilot study about the treatment of this disease. METHODS: From April 1999 to June 2000, we enrolled 11 chemotherapy-naïve patients with inoperable malignant pleural mesothelioma suitable to receive the following combination chemotherapy: raltitrexed, 3 mg/m2 iv, and oxaliplatin, 130 mg/m2, as a 2-hr infusion every 3 weeks. RESULTS: Four partial responses, 1 regression of disease (objective response rate, 45%; 95% CI, 15.6-74.4%), 4 stable diseases and 2 progressions of disease were observed. An improvement in disease-related symptoms was recorded in all responders and in 2 patients with stable disease. Toxicity was mild, with no toxic-related death and only 1 episode of grade 4 neurotoxicity. CONCLUSIONS: We consider the combination promising and worthy of further studies.

Multicenter evaluation of the XT modular coronary stent: clinical and angiographic results.

BACKGROUND: In the past few years, the indications for stent implantation have broadened, along with a larger number of available designs. The Bard XT stent is a new modular stent with an original structure and design. METHODS: To evaluate the new Bard XT stent, we studied its use in a multicenter experience in 163 patients, with a total of 168 lesions and 180 implanted units. RESULTS: Despite the predominance of complex lesions, the procedural success rate was 98%, with only a 2% failure of stent implantation. There was only one death (no-reflow phenomenon in a rescue primary PTCA in a patient in cardiogenic shock) without other major periprocedural complications. Centralized QCA showed a statistically significant increase of MLD (from 0.73 +/- 0.43 mm to 2.71 +/- 0.40 mm, p < 0.0001) and DS reduction (from 73.8 +/- 15.1% pre-treatment to 7.8 +/- 0.4% after stent implantation; p < 0.0001). Aspirin and ticlopidine were routinely administered after the procedure. Thirty-day follow-up reported only one case of subacute stent thrombosis (in the first day), treated with re-PTCA. CONCLUSIONS: In a group of patients with complex lesions, we obtained a high rate of success with a low incidence of complications. The Bard XT stent had a high-performance profile with normalization of vessel diameter and angiographic results similar to the ones obtained with the "slotted tube" stents.

Combined epirubicin and interleukin-2 regimen in the treatment of malignant mesothelioma: a multicenter phase II study of the Italian Group on Rare Tumors.

The Italian Group on Rare Tumors undertook a phase II study of a combination of epirubicin and interleukin-2 in 21 chemotherapy-naive patients with malignant mesothelioma. All patients had bidimensionally measurable disease at CT scan. Treatment included Intravenous administration of epirubicin at a dose of 110 mg/m2 i.v. on day 1, and interleukin-2 at a dose of 9 MU subcutaneously from day 8 to day 12 and from day 15 to day 19. Cycles were repeated every three weeks, up to six times in the absence of progressive disease. Treatment response was evaluated after two cycles of therapy. Only one patient achieved a partial response, resulting in an overall response rate of 5% (1/21) with a median progression-free and overall survival of 5 and 10 months, respectively. Toxicity was relevant and caused treatment discontinuation in many patients. These results do not support the use of such a combination in the management of malignant mesothelioma.

Left ventricular function and exercise tolerance in patients with type II diabetes mellitus.

BACKGROUND: Left ventricular (LV) preload changes may alter exercise tolerance (ET), probably lessening activation of the Maestrini-Starling mechanism. Reduced LV filling (pre-load) during the diastolic phase, usually impaired in diabetic patients, could affect ventricular function. HYPOTHESIS: To evaluate the relationship between some echocardiographic LV function indices and ET, 24 patients (age 43-75 years, mean 54 +/- 13 years, Group A) with type II diabetes mellitus (DM), not suffering from other pathologies, and for whom the ergometric stress test (EST) resulted in an early interruption because of muscular fatigue and/or dyspnea, and 14 patients (age 38-70 years, mean 53 +/- 12 years, Group B) with type II DM and maximal ergometric stress test, used as control group, were studied. METHODS: The EST was performed by increasing the load by 25 W every 2 min; its duration was used as an ET index and correlated with clinical parameters of LV function obtained with M-mode, two-dimensional, and Doppler echocardiography. RESULTS: No patients in either Group A or Group B showed a high systolic blood pressure value at rest and/or an LV hypertrophy and/or an alteration of systolic functional indices. In neither group was there significant correlation between ET and duration of DM, basal heart rate, basal and max systolic blood pressure, and EF values. Linear regression analysis showed a significant correlation between Doppler parameters of the diastolic function and ET index in Group A, while there was no significant correlation in Group B. CONCLUSION: From these data we can deduce that in absence of left systolic ventricular dysfunction the impairment of LV relaxation in DM can influence exercise tolerance, probably by limiting activation of the contractile reserve.

Left ventricular performance and autonomic dysfunction in patients with long-term insulin-dependent diabetes mellitus.

Cardiac autonomic neuropathy (CAN) is a very frequent complication of insulin-dependent mellitus type 1, affecting the sympathetic or parasympathetic sections or both. The different impairment in the two sections might modify left ventricular function early. To evaluate this relationship, we studied 61 patients (mean age 39.6 +/- 7 years) with type 1 diabetes for more than 10 years, without coronary artery disease (CAD); negative ergometric stress test) and without other pathologies that could interfere with ventricular function. All patients underwent MONO-, 2-dimensional and Doppler echocardiographic examination and radionuclide angiography with 99Tc (RNA). According to the outcome of the Ewing tests, patients were divided into two groups: group A with two or more tests altered (26 patients with CAN) and group B with one or no tests altered (35 patients without CAN). No significant differences between the two groups were found in the systolic function parameters with either technique. In contrast, a pattern of abnormal relaxation was found for the diastolic function parameters: in group A a decrease in E-wave velocity and its time-velocity integral and an increase in A-wave and its time-velocity integral were detected with echocardiography. Moreover, RNA showed a reduced peak filling rate and an increased isovolumic relaxation time. When compared with normal values, an abnormal diastolic filling, defined as two independent echocardiography plus one RNA variable impairment, was found in 15 patients (57.6%) in group A and in only 4 patients (11.4%) in group B (P < 0.001). Our findings suggest an early involvement of diastolic function in patients with CAN.

[Clinical value of multiplane transesophageal echocardiography in the diagnosis of lipomatous hypertrophy of the interatrial septum. Report of two clinical cases]. / Utilità clinica dell'ecocardiografia transesofagea multiplanare nella diagnosi di ipertrofia lipomatosa del setto interatriale. Descrizione di due casi clinici.

Lipomatous hypertrophy of interatrial septum is a very rare condition associated with supraventricular arrhythmias and sudden death. The authors describe two clinical cases of lipomatous hypertrophy and underline usefulness of multiplane transesophageal echocardiography in the diagnosis of this affection.

[Atrial septal aneurysm. Report of two clinical cases and review of the literature]. / Aneurisma del setto interatriale. Descrizione di due casi clinici e revisione della letteratura.

We report two cases of atrial septal aneurysm, one associated with paroxysmal supraventricular tachycardia, the second with atrial septal defect. In both cases there were verified some transitory ischemic attacks. Carotid ultrasonography excluded atherosclerosis lesions. Two-dimensional transthoracic echocardiography showed an atrial septal aneurysm which, in the second case, was associated with atrial septal defect as demonstrated by color Doppler. The therapy is discussed in the case of septal atrial aneurysm associated with transitory ischemic attack, anticoagulant therapy is indicated; in the other, surgical correction of the defect is necessary.

[Asymptomatic atrial septal aneurysm: is anticoagulant therapy always necessary? Considerations on a clinical case and evaluation of a correct cost-benefit ratio]. / Aneurisma del setto interatriale asintomatico: è sempre necessaria la terapia anticoagulante? Considerazioni su di un caso clinico e sulla valutazione di un corretto rapporto costo-beneficio.

Atrial septal aneurysm is a cardiac abnormality with thromboembolic potential; in patients with this lesion and parameters of risk of embolic events long-term anticoagulant therapy is indicated. A clinical case of a young woman with atrial septal aneurysm and low risk parameters of cardioembolic stroke was presented.

[Ambulatory monitoring of arterial pressure in the diagnosis and therapeutic evaluation of dysautonomic diseases: observations in a case of Shy-Drager syndrome]. / Il monitoraggio dinamico della pressione arteriosa nella diagnosi e valutazione terapeutica delle affezioni disautonomiche: osservazioni in un caso di sindrome di Shy-Drager.

Shy-Drager syndrome is a very rare disease affecting the autonomic nervous system. Usefulness of beta-adrenergic chronic therapy has already been focused in these cases. Ambulatory blood pressure monitoring may help to study the cardiocirculatory adaptation in Shy-Drager syndrome patients.

[Cardiovascular adaptation to the stress test in subjects with Cooley's disease]. / Adattamenti cardiovascolari al test da sforzo in soggetti affetti da morbo di Cooley.

Thalassaemia major determines an impaired effort tolerance because of a condition of severe anaemia, progressive left ventricular dysfunction, pulmonary circulation compromise. The aim of our study is to evaluate haemodynamic response to exercise in thalassaemic patients without clinical features of heart failure. We have selected 13 patients affected by thalassaemia major (Thal+; 10-18 years). Each patient was transfused when haemoglobin values were < 9-9.5 g/dl and was treated with desferrioxamine (40 mg/kg sc) when serum ferritin values were > 2,000 ng/ml. Thal+ patients were compared with normal subjects (Thal- 10-16 years). No patient assumed hypotensive therapy, no had familiar history of hypertension. Both groups have undergone an ergometric stress test at the cycloergometer, with increase of 25 W every 2 min, up to the reaching of the maximum age-related heart rate, or up to muscle exhaustion or unbearable dyspnea, followed by a 10 min recovery phase. The following parameters were taken in consideration: systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), the product of the heart rate by the systolic blood pressure (DP), at rest, at the maximum common work (MCW), at maximum stress and in the recovery phases. At rest, only DP showed significant differences between the two groups: in Thal+ patients higher than in Thal- (p = 0.045). At the MCW, Thal+ patients had SBP (p = 0.019), DBP (p = 0.01), HR (p = 0.035) and DP (p = 0.003) higher than Thal- patients. At maximum stress only DBP showed significant differences in Thal+ patients (p = 0.019), although Thal+ patients achieved lower levels of workload (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of lithium carbonate on cytokine production in patients affected by breast cancer.

It has been reported that lithium salt compounds influence hematopoiesis, which is known to be regulated by a number of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6). Since lithium can induce TNF production in human monocytes, we wished to determine if lithium carbonate treatment of neutropenic patients affected by breast cancer results in increased cytokine production. Serum levels of TNF alpha, IL-1 and IL-6 were measured before and at 7 and 180 days after treatment with lithium carbonate. Results indicate that this therapy produced TNF alpha and IL-6, but not IL-1 alpha, elevations in patients affected by unmetastasized breast cancer. Conversely, TNF alpha, but not IL-6, elevations were detected in metastatic patients. Studies are under way to investigate the mechanisms by which lithium salts affect cytokine production in monocytes from cancer patients.

[Arterial pressure in obese subjects during ergometric stress test and recovery]. / Comportamento della pressione arteriosa in soggetti obesi durante sforzo e nel recupero.

In obesity, the systemic resistances (SR) are reduced while the blood volume is increased. The rise of cardiac output (CO), stress-induced, produces an increase in blood pressure (BP), as an hypertensive behavior of the stress-response. The aim of our study is to evaluate if, in obese subjects, the considerable increase of BP is more related to the rise of CO than to the rise of SR. For this reason we studied the behavior of BP through indexes derived from the ratio of SBP values at the 1st, 3rd, 5th, 10th minutes of the recovery by the SBP value at the acme of stress. These indexes are under neurovegetative control, and were shown to be impaired in hypertensive pts. The results of ergometric stress test (EST) of 37 obese subjects (Ob+) (27 males and 10 females, mean age 46.2 +/- 7.3 years), determined according to Lorentz's formula, was compared with the parameters deduced from the EST of 18 normal subjects (Ob-) (13 males and 5 females, mean age 36.7 +/- 8.5). The exercise showed an increase, more pronounced in Ob+ subjects, of SBP and DBP, and this also persisted in the recovery phase. Although BP was significantly higher in the Ob+group, the SBP indexes did not differ in the two groups. Then, from these data it can be deduced that, although during EST in obese subjects there is an absolute increase of BP and this persists in the recovery phase, the behavior of this parameter probably cannot be related to alteration of neurovegetative system as demonstrated by the normal SBP indexes.