Dramatic response to regorafenib in early glioblastoma progression: case report and review of the literature.

BACKGROUND: Glioblastoma (GBM) is a highly lethal disease despite integrated treatment comprising radiotherapy plus concomitant and adjuvant temozolomide, with a median overall survival of less than 15 months. For recurrent glioblastoma, there is yet no standard therapy, considering that Bevacizumab have failed to improve overall survival (OS) while regorafenib had a little benefit over standard chemotherapy. In addition, the disease control rate is almost exclusively stability, with a poor objective response rate. CASE REPORT: Here we present a case of rapid response to regorafenib in early glioblastoma progression at the end of adjuvant radiotherapy: after a single cycle of regorafenib the patient observed an impressive improvement in clinical condition, disappearance of headaches and a clear reduction of neoplastic tissue in MRI. A brief review about new radiological patterns in Magnetic Resonance Imaging (MRI) related to the introduction in clinical practice of antiangiogenic drugs and tyrosine kinase inhibitors has also been carried out. CONCLUSIONS: Regorafenib was certainly a first turning point in the second-line treatment of GBM, showing longer response rates and mostly disease stability than bevacizumab. A switch-maintenance strategy with tyrosine kinase inhibitors may represent a valid second-line therapeutic option.

Risk stratification for arrhythmic events in patients with nonischemic dilated cardiomyopathy and nonsustained ventricular tachycardia: role of programmed ventricular stimulation and the signal-averaged electrocardiogram.

OBJECTIVES: This study investigated prediction of arrhythmic events by the signal-averaged electrocardiogram (ECG) and programmed stimulation in patients with nonischemic dilated cardiomyopathy. BACKGROUND: Risk stratification in patients with nonischemic dilated cardiomyopathy remains controversial. METHODS: Eighty patients with nonischemic dilated cardiomyopathy and spontaneous nonsustained ventricular tachycardia underwent signal-averaged electrocardiography (both time-domain and spectral turbulence analysis) and programmed stimulation. All patients were followed up for a mean of 22 +/- 26 months. RESULTS: Sustained monomorphic ventricular tachycardia was induced in 10 patients (13%), who all received amiodarone. The remaining 70 patients were followed up without antiarrhythmic therapy. Of the 80 patients, 15% had abnormal findings on the time-domain signal-averaged ECG, and 39% had abnormal findings on spectral turbulence analysis. Time-domain signal-averaged electrocardiography had a better predictive accuracy for induced ventricular tachycardia than spectral turbulence analysis (88% vs. 66%, p < 0.01). During follow-up, there were 9 arrhythmic events (5 sudden deaths, 4 spontaneous ventricular tachycardia/fibrillation) and 10 nonsudden cardiac deaths. Cox regression analysis showed that no variables predicted arrhythmic events or total cardiac deaths. The 2-year actuarial survival free of arrhythmic events was similar in patients with or without abnormal findings on the signal-averaged ECG or induced ventricular tachycardia. CONCLUSIONS: In patients with nonischemic dilated cardiomyopathy, 1) there is a strong correlation between abnormal findings on the time-domain signal-averaged ECG and induced ventricular tachycardia, but both findings are uncommon; and 2) normal findings on the signal-averaged ECG, as well as failure to induce ventricular tachycardia, do not imply a benign outcome.

The signal-averaged electrocardiogram and ventricular arrhythmias after thrombolysis for acute myocardial infarction.

The prevalence of an abnormal signal-averaged electrocardiogram (ECG) and ventricular arrhythmias on 24 h ambulatory electrocardiography was evaluated in 118 patients 13 +/- 2 days after acute myocardial infarction. Group 1 (46 patients) underwent intravenous thrombolysis within 6 h of the onset of symptoms, whereas Group 2 (72 patients) did not. An abnormal signal-averaged ECG was seen in 15% of patients in Group 1 and 21% of those in Group 2 (difference not significant). The number of ventricular premature complexes/h was lower in Group 1 than in Group 2: 2.58 +/- 1.63 versus 7.91 +/- 10.75 (p less than 0.01). However, complex arrhythmias (greater than or equal to 10 ventricular premature complexes/h or ventricular tachycardia) were equally common in Groups 1 and 2 (20% versus 22%, respectively). Their prevalence was similar in patients with or without an abnormal signal-averaged ECG (29% versus 18%, respectively, in Group 1 and 27% versus 21%, respectively, in Group 2). Comparison between patients with (n = 26) or without (n = 20) angiographic patency of the infarct-related coronary artery after thrombolysis showed no significant difference in the prevalence of an abnormal signal-averaged ECG (8% versus 25%, respectively) and complex ventricular arrhythmias (19% versus 20%, respectively). These data suggest that thrombolysis does not affect the prevalence of complex ventricular arrhythmias and an abnormal signal-averaged ECG or their relation after acute myocardial infarction.

Risk stratification and management of patients with organic heart disease and nonsustained ventricular tachycardia: role of programmed stimulation, left ventricular ejection fraction, and the signal-averaged electrocardiogram.

PURPOSE: Programmed stimulation, left ventricular ejection fraction, and signal-averaged electrocardiography were performed in patients with organic heart disease and spontaneous nonsustained ventricular tachycardia (VT) to determine the role of these techniques in risk stratification and management. PATIENTS AND METHODS: The study consisted of 90 patients: 63 had coronary artery disease and 27 had idiopathic dilated cardiomyopathy. Radionuclide ventriculography, signal-averaged electrocardiography, and programmed electrical stimulation were performed in all patients within 48 hours of index ambulatory electrocardiography. RESULTS: Fifty-three patients (59%) had an ejection fraction less than 40%. Programmed stimulation induced sustained monomorphic VT in 22 patients (24%), ventricular fibrillation (VF) in 10 patients (11%), and no sustained VT/VF in 58 patients (64%). The signal-averaged electrocardiogram (ECG) showed late potentials in 23 patients (26%). Sustained monomorphic VT could be induced in 65% of patients with late potentials and in 10% of those without late potentials. There was no case of inducible sustained monomorphic VT in 33 patients with no late potentials and an ejection fraction of 40% or greater. All patients with induced sustained monomorphic VT received antiarrhythmic therapy guided by the results of programmed stimulation. All 58 patients with no induced sustained ventricular tachyarrhythmias and eight patients with induced VF were discharged without receiving antiarrhythmic drugs. During a follow-up of 30 +/- 10 months, the three-year sudden death rate was 19% in patients with induced sustained VT, 0% in those with induced VF, and 9% in those with no induced sustained VT/VF. The three-year sudden death rate was the same (7%) in patients with no induced sustained VT/VF, both in those with an ejection fraction of 40% or greater or less than 40%. On the other hand, the three-year total cardiac mortality was significantly higher (27%) in those patients with ejection fractions less than 40% compared to those with ejection fractions of 40% or greater (7%). CONCLUSION: It is concluded that the signal-averaged ECG, ejection fraction, and programmed stimulation could be used for the risk stratification and management of patients with organic heart disease and nonsustained VT as follows: (1) Patients with no late potentials and with an ejection fraction of 40% or greater do not require invasive evaluation or antiarrhythmic therapy, since the incidences of induced VT and sudden death are very low. (2) Patients with late potentials as well as patients without late potentials but with an ejection fraction of less than 40% may be advised to undergo electrophysiologic evaluation.(ABSTRACT TRUNCATED AT 400 WORDS)

Spontaneous myocardial ischemia and the signal-averaged electrocardiogram.

The effects of transient myocardial ischemia on the signal-averaged electrocardiogram were investigated in 13 patients with coronary artery disease and spontaneous angina undergoing 3-channel ambulatory electrocardiography. Ischemia was seen as ST elevation in 2 patients or ST depression in 11; it was anterior in 5 patients, inferior in 4 and undefined in 4. Signal-averaged electrocardiograms with noise levels less than or equal to 1 microV were obtained from Holter tapes during 54 of 61 ischemic attacks recorded in the study group (88%), and compared with 54 tracings recorded within 60 minutes of the index attacks. Baseline tracings were normal in 8 patients (62%), showed a long QRS duration in 2 (15%), and both a long QRS duration and a late potential in the remaining 3 (23%). Comparison of recordings at baseline and during ischemic attacks revealed no significant changes in signal-averaged electrocardiographic parameters. Absence of significant differences was also noted when analysis was performed according to the type of ischemic attacks (associated with ST elevation [n = 14] or ST depression [n = 40]), their location (anterior [n = 21] or inferior [n = 23]), their duration (greater than 10 minutes [n = 29] or less than or equal to 10 minutes [n = 25]), and their magnitude (greater than 2 mm [n = 18] or less than or equal to 2 mm [n = 36]). It is concluded that spontaneous transient myocardial ischemia, independent of its type, location, duration and magnitude, does not generate a substrate for late potentials on the signal-averaged electrocardiogram.

Value of the signal-averaged electrocardiogram as a predictor of the results of programmed stimulation in nonsustained ventricular tachycardia.

A prospective assessment of several clinical variables, left ventricular function indexes, Holter recording characteristics and signal-averaged electrocardiogram (ECG) for their value in predicting the inducibility of sustained ventricular tachyarrhythmias was carried out in a consecutive series of 105 patients with nonsustained ventricular tachycardia (VT). The patients were divided into 3 groups based on the results of programmed electrical stimulation: group 1, 22 patients with induced sustained monomorphic VT; group 2, 14 patients with induced ventricular fibrillation (VF) and group 3, 69 patients with no induced sustained VT/VF. Left ventricular ejection fraction less than 0.40, history of syncope/presyncope and abnormal signal-averaged ECG were significantly more common in group 1 than in group 3. No significant difference was found between groups 2 and 3. The sensitivity, specificity and predictive accuracy of the signal-averaged ECG for the induction of sustained monomorphic VT were 64, 89 and 84%, respectively. Using stepwise discriminant function analysis, the signal-averaged ECG was found to be the single most accurate screening test to predict the inducibility of sustained VT in patients with nonsustained VT and its value was independent of the etiology of heart disease and the length of spontaneous runs. Because of the very high specificity and negative predictive accuracy, patients with normal signal-averaged ECGs may not require invasive evaluation.

Role of bandpass filters in optimizing the value of the signal-averaged electrocardiogram as a predictor of the results of programmed stimulation.

Normal values for the signal-averaged electrocardiogram (SAECG) at 11 different high-pass filter settings were obtained from 100 normal subjects (group I). The filtered QRS duration and the duration of low amplitude signals less than 40 microV, but not the root mean square voltage of the last 40 ms (RMS40), showed normal distribution. A normal distribution for RMS40 could be obtained by transforming each value to its natural logarithm. The normal values were used in a systematic approach to optimize the accuracy of the SAECG to predict the results of programmed stimulation in 80 patients with spontaneous nonsustained ventricular tachycardia (VT). Fifty-two patients with no inducible VT (group II) and 28 patients with inducible sustained monomorphic VT (group III) were investigated. The 3 SAECG parameters at each high-pass filter in groups II and III were categorized as normal or abnormal and were evaluated singly or in combinations of 2 or 3. There was no combination that provided a sensitivity greater than 82% that could also be obtained by single determinations of low amplitude signals less than 40 microV at 25 to 40 Hz or RMS40 at 40 Hz. On the other hand, there were 267 different combinations that provided a maximal specificity of 98%. The best total predictive accuracy of a single parameter was 85%, provided by RMS40 at 40 or 60 Hz. The total predictive accuracy could be improved to 89% by 1 of 32 different combinations. The top combinations were mostly in triplets and included SAECG parameters recorded at different high-pass filter settings. The only 2 paired combinations with the best total predictive accuracy were RMS40 at 20 or 25 Hz paired with RMS40 at 40 Hz. Frequencies at both ends of the analyzed high-pass filter settings (less than 20 Hz and greater than 60 Hz) were not represented in the top predictive combinations. The SAECG parameters analyzed at 40 Hz were most frequently represented in the top predictive combinations, suggesting that the SAECG may have the best predictive accuracy at this filter setting. In summary, the combination of SAECG parameters analyzed at different filter settings can enhance the accuracy of the technique as a screening test for the results of programmed stimulation in patients with spontaneous nonsustained VT.

Radiofrequency ablation for cardiac arrhythmias causing postcardiac injury syndrome.

We report 2 cases of exudative left pleural effusion following radiofrequency catheter ablation of cardiac arrhythmias complicated by cardiac perforation. We suggest that radiofrequency ablation may be a previously unsuspected cause of postcardiac injury syndrome.

Relation of prognosis in sick sinus syndrome to age, conduction defects and modes of permanent cardiac pacing.

A large population of sick sinus syndrome (SSS) patients was analyzed to determine whether age of patients, presence of conduction disturbances and mode of permanent pacing are related to the occurrence of supraventricular tachyarrhythmias, cerebral embolism and cardiac mortality. Three hundred thirty-nine patients permanently paced (135 AAI, 79 DDD, 125 VVI) because of SSS were followed for a mean period of 5 years (range 2 to 10). Patients were divided into 4 groups according to age (less than 70 or greater than 70 years) and the presence or absence of an associated conduction disturbance. Sixty-eight percent of VVI, 55% of AAI and 40.5% of DDD patients were greater than 70 years of age. In the VVI and DDD groups a conduction disturbance was present in 67 of 204 (33%) patients; conduction disturbances were more common in patients greater than 70 years old (46 of 111, 41%) than in those less than 70 years old (21 of 93,22%). The Wenckebach threshold (greater than 140 beats/min) remained unchanged during the follow-up period in 82% of AAI patients. In 9% of these patients, the Wenckebach threshold showed some degree of deterioration, but only in 2 patients was it less than 100 beats/min (1.5%). Spontaneous second-degree atrioventricular block was observed in 7 patients (5%); it disappeared in 6 of these patients when drug therapy was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence, time course and malignancy of ventricular arrhythmia during spontaneous ischemic ST-segment depression.

Ventricular arrhythmias during transient myocardial ischemia were studied in 60 patients with spontaneous angina and greater than or equal to 1 ischemic attack with ST-segment depression during 24-hour ambulatory electrocardiography. The patients were divided into 2 groups: group 1, 10 patients (17%) who developed ventricular arrhythmias during 26 of 92 (28%) ischemic attacks; and group 2, 50 patients who did not show this phenomenon. Daily ischemic attacks, total ischemic time and the proportion of symptomatic ischemic attacks were significantly greater (p less than 0.01) in group 1 versus group 2. In group 1 patients, ischemic attacks were found to have twice the duration in the presence of arrhythmias than in their absence (20.4 +/- 11.9 vs 9.1 +/- 8.4 minutes, p less than 0.01); arrhythmias were more common during symptomatic than during silent ischemic attacks (39 vs 13%, p less than 0.02). Arrhythmias occurred at the onset or peak of ST-segment depression (ischemia phase) in 6 cases (60%), during the resolution of ST-segment depression (recovery phase) in 2 cases (20%) and during both phases of ischemic attacks in the remaining 2 (20%). When compared to recovery phase arrhythmias, ischemia phase arrhythmias were characterized by a later onset time (173 +/- 144 vs 58 +/- 54 seconds, p less than 0.01) and a longer duration (105 +/- 107 vs 41 +/- 22 seconds, p less than 0.01). During the ischemia phase, 16 of 353 ventricular premature complexes initiated ventricular tachycardia, while during the recovery phase only 1 of 161 ventricular premature complexes resulted in ventricular tachycardia (4.5 vs 0.6%, p less than 0.02). Thus, ventricular arrhythmias may accompany spontaneous ischemic ST-segment depression, when the latter is recurrent, prolonged and symptomatic; arrhythmias are characterized by a greater frequency, duration and malignancy during the ischemia phase than during the recovery phase of ischemic attacks.

Incidence and prediction of induced ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy.

The value of time-domain and spectral turbulence analyses of the signal-averaged electrocardiogram (SAECG) for predicting induction of sustained monomorphic ventricular tachycardia (VT) was prospectively investigated in 70 patients with idiopathic dilated cardiomyopathy. Sustained VT was induced in 9 patients (13%). The prevalence of abnormal time-domain and spectral analyses was 16 and 37%, respectively. The total predictive accuracy of time-domain and spectral analyses for VT induction was 86 and 67%, respectively (p < 0.01). The predictive accuracy of time-domain and spectral analysis was similar in patients without an intraventricular conduction defect (94 and 84%, respectively). However, the predictive accuracy of time-domain was higher than that of spectral analysis in patients with an intraventricular conduction defect (65 vs 25%; p < 0.05). The poor concordance between spectral analysis and programmed stimulation results was mainly due to the high number of false-positive recordings in the presence of an intraventricular conduction defect (9 of 20 cases). With the use of stepwise discriminant function analysis, an abnormal time-domain SAECG was the only variable predicting the induction of sustained VT (p < 0.0003). In dilated cardiomyopathy, an abnormal time-domain SAECG and induced sustained VT are rare, both time-domain signal-averaged electrocardiography and spectral analysis have a high predictive accuracy for VT induction in patients without an intraventricular conduction defect, and spectral analysis does not improve VT prediction in those with a conduction defect.

Lack of correlation between transient myocardial ischemia and late potentials on the signal-averaged electrocardiogram.

The relation between transient myocardial ischemia and late potentials was investigated in 100 patients with coronary artery disease who underwent serial recordings of the signal-averaged electrocardiogram before, during and after dipyridamole infusion. During this test, 47 patients (group 1) developed transient myocardial ischemia (with ST elevation in 14 cases and ST depression in 33), whereas 53 patients (group 2) did not. Baseline signal-averaged electrocardiogram was abnormal in 20 patients (20%): a QRS duration greater than 115 ms was seen in 6 patients, a late potential (root mean square voltage of last 40 ms of QRS [RMS40] less than 25 microV) in 9, both abnormalities in 5, with no significant differences between groups 1 and 2 (26 vs 15%, respectively). In both groups, comparison of recordings obtained before, during and after dipyridamole test revealed no significant changes in QRS duration and RMS40. Absence of significant differences was also observed when patients with transient ischemic ST elevation or ST depression were examined separately. During the test, 100% of abnormal basal recordings remained abnormal and 98% of normal recordings remained within normal limits. In only 2 patients (from group 1) RMS40, which showed borderline values at baseline, decreased to abnormal values during dipyridamole test. These data suggest that electrophysiologic abnormalities induced by transient myocardial ischemia may not bear any relation with the substrate for chronic reentrant ventricular tachyarrhythmias, as reflected by late potentials on the signal-averaged electrocardiogram.

Alternans of the ST segment in variant angina. Incidence, time course and relation to ventricular arrhythmias during ambulatory electrocardiographic recording.

The ST alternans was recorded during at least one ischemic attack with ST elevation in nine of 65 patients with variant angina. The magnitude and duration of ST elevation during ischemic attacks were significantly greater in patients with than in those without ST alternans. It always appeared during the occlusion phase and disappeared during the reperfusion phase of ischemic attacks. In patients with episodic ST alternans, the ischemic attacks showed a greater ST elevation and a longer duration in the presence of ST alternans than in its absence. The incidence of occlusion phase ventricular arrhythmias was greater in patients with than in those without ST alternans; the incidence of reperfusion phase ventricular arrhythmias was similar in the two groups. The ST alternans always preceded the onset of occlusion phase arrhythmias. Thus, in variant angina, ST alternans represents an index of the severity of ischemia and a precursor of ventricular arrhythmias.

Phase I-II study of gemcitabine and paclitaxel in pretreated patients with stage IIIB-IV non-small cell lung cancer.

Gemcitabine and paclitaxel are among the most active new agents in non-small cell lung cancer (NSCLC) and are worth considering for second-line chemotherapy. In this phase I-II study, we combined gemcitabine and paclitaxel for second-line treatment of advanced NSCLC. Gemcitabine doses were kept fixed at 1000 mg/m2 on day 1 and 8, and paclitaxel doses were escalated from 90 mg/m2 on day 1 of the 21-day cycle. Thirty-seven patients were treated at six different dose levels. Grade 4 neutropenia was dose-limiting toxicity (DLT), since it occurred in two out of six patients treated at paclitaxel 240 mg/m2; the paclitaxel dose level just below (210 mg/m2) was selected for phase Il evaluation. Non-hematologic toxicity was mild. One complete response (CR) (3%) and 13 partial responses (PR) (36%) were observed in 36 evaluable patients for an overall response rate of 39% (95% C.I., 23-57%). Median duration of response was 35 weeks (range, 8-102). All of the observed objective responses occurred in the 19 patients who had previously responded to the first-line therapy. Median survival was 40 weeks (range, 8-108 weeks). The combination of gemcitabine and paclitaxel is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC; further evaluation, at least in selected patients, such as those previously responding to first-line chemotherapy, is definitely warranted.

Transient myocardial ischemia detected by Holter monitoring during the early post-infarction period.

BACKGROUND: On the basis of extensive studies concerning the prognostic value of Holter monitoring in patients with angina, we evaluated the clinical outcome of patients with transient ischemic episodes soon after myocardial infarction. METHODS: The incidence and clinical significance of myocardial ischemia, detected in the acute phase of myocardial infarction, were evaluated in 87 patients. Twenty-four-hour Holter recordings were obtained on the 2nd, 4th, 6th, and 12th hospital day. RESULTS: Myocardial ischemia was detected during at least one of the four recording periods in 28 patients (32%). A total of 157 ischemic episodes were documented. The proportion of recordings that showed transient myocardial ischemia progressively declined from 20% on the 2nd day to 5% on the 12th post-infarction day. Of the 157 ischemic episodes, 132 (84%) were silent and 25 (16%) were symptomatic. Transient ST-segment elevation was present in 99 of the 157 episodes (63%), while transient ST-segment depression occurred in the remaining 58 of the 157 cases (37%). One or more in-hospital cardiac events (reinfarction, acute pulmonary edema, ventricular tachycardia or fibrillation, cardiac death) were more frequent in patients with (group I) than in those without (group II) transient myocardial ischemia [nine out of 28 (32%) versus six out of 59 (10%); P < 0.03]. At follow-up (mean 11.5 +/- 2 months) the incidence of cardiac events (angina, reinfarction, heart failure, ventricular tachycardia or fibrillation, revascularization procedures, cardiac death, sudden death) was comparable in the two groups [four out of 24 (17%) versus 10 out of 49 (20%); NS]. Predischarge exercise testing, performed in 64 patients (74%), showed myocardial ischemia in 50%; the percentage did not vary significantly between group I and group II patients. Moreover, a positive exercise test was not predictive of major cardiac events at follow-up. CONCLUSION: Transient myocardial ischemia, frequently silent, is not uncommon in the acute phase of myocardial infarction and progressively decreases during the in-hospital stay. Its recognition in the subacute phase of myocardial infarction may lead to the identification of a subset of patients at the highest risk of early major complications, who may benefit from aggressive diagnostic and therapeutic strategies.

Phase I dose escalation study of gemcitabine and paclitaxel plus colony-stimulating factors in previously treated patients with advanced breast and ovarian cancer.

Gemcitabine and paclitaxel (PTX) are among the most active new drugs in advanced breast and ovarian cancer. In this Phase I study, we used fixed doses of gemcitabine administered on days 1 and 8 and escalating doses of paclitaxel on day 1 of a 21-day cycle in patients with pretreated metastatic breast or ovarian cancer. The dose of gemcitabine was fixed at 1,000 mg/m2; PTX was commenced in the first small patient group at a dose of 90 mg/m2, which was then escalated in subsequent groups by 30 mg/m2 per step. From the third dose level onwards, all patients received granulocyte colony-stimulating factor 300 microg by subcutaneous injection on days 5 and 6, and granulocyte macrophage colony-stimulating factor on days 15-18. Cohorts of at least 3 patients were treated at each dose level. Dose escalation was stopped if at least a third of the patients in a given cohort had dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia, or grade 3-4 non-haematological toxicity. The maximum tolerated dose (MTD) was defined as the dose level immediately below that causing DLT in one-third of the patients or more. Evaluation of the tumour response was performed every three cycles. Forty-five patients (31 with breast cancer, 14 with ovarian cancer) were treated at seven different dose levels. Only at the seventh PTX dose level was DLT observed after the first course of therapy: three grade 4 neutropenia, one grade 4 thrombocytopenia, and one grade 4 anaemia. DLT occurred in 5/6 patients at at PTX dose of 270 mg/m2; therefore dose escalation was stopped at that level and the dose immediately before it (PTX 240 mg/m2) was considered as the MTD and recommended for further studies. No toxic deaths occurred. Grade 3-4 uncomplicated neutropenia was observed in four patients. Three had uncomplicated grade 3-4 thrombocytopenia. One patient had grade 3 and one grade 4 anaemia. Nonhaematological side effects were generally mild. Among 30 evaluable patients with metastatic breast cancer, four complete responses (CR) (13%) and 12 partial responses (PR) (40%) were observed, for an overall response rate of 53% (95% confidence interval (CI) 34-72). The median duration of response was 31 weeks. Among 13 evaluable patients with advanced ovarian cancer, one CR (8%) and five PRs (38%) were observed, for an overall response rate of 46% (95% CI 19-78). The median duration of response was 32 weeks. Our study shows that gemcitabine and PTX can be administered in combination in patients with breast and ovarian cancer without unexpected toxicities and with encouraging therapeutic results.

Antiarrhythmic effects of oral indecainide in patients with ventricular tachyarrhythmias.

In order to assess the efficacy and safety of oral indecainide in patients with serious ventricular arrhythmias we studied 11 patients with high-grade ventricular ectopy and ventricular tachycardia (VT) which were refractory to therapy with at least one standard antiarrhythmic drug. Spontaneous arrhythmias were quantitated by 24-h Holter monitor before and during therapy with indecainide. Spontaneous VT was sustained in 4 patients and nonsustained in 7. Ten patients underwent baseline electrophysiologic study (EPS) and VT was induced in 9. The mean ejection fraction was 25 +/- 14%. Indecainide was given orally at a dose of 211 +/- 118 mg/day. The frequency of ventricular premature beats (VPBs) was significantly (greater than 85%) decreased in 90% of patients, while ventricular couplets frequency decreased in 78%. Spontaneous VT was abolished in 5 of 11 (45%). Sustained VT was induced in 5 of 7 (71%) patients who underwent follow-up EPS. The QRS duration was significantly prolonged during therapy (0.13 +/- 0.04 s) compared to control (0.10 +/- 0.02 s). The PR, QTc, and JTc intervals were not significantly changed. Indecainide was well tolerated, but 2 patients died of ventricular tachyarrhythmias while receiving the drug. Indecainide suppressed VPBs in a high percentage of patients, but was much less successful in controlling VT. Caution is necessary when using this drug because of its potential for exacerbation of arrhythmia.

Analysis of interleukin-2/interleukin-2 receptor system in advanced non-small-cell lung cancer.

AIMS AND BACKGROUND: The purpose of the study was to investigate the IL-2/IL-2 receptor system in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sera from 40 subjects and 80 patients with stage III and IV NSCLC were assayed for soluble interleukin-2 receptor (sIL-2R) and interleukin-2 (IL-2) by the enzyme-linked immunosorbent assay. Circulating CD25+ cells were analyzed by flow cytoflorimetry. The data were related to clinical status by comparing the levels of sIL-2R and IL-2 at diagnosis and during the treatment. RESULTS: The mean sIL-2R concentrations of the NSCLC patients were significantly higher than the control population (P=0.0001); the patients with metastatic disease had significantly higher levels than those with locally advanced disease (P=0.02). No correlation was seen between circulating CD25+ cells and sIL-2R levels. Disease progression was associated with an increase in sIL-2R levels and a decline in IL-2; the sIL-2R/IL-2 ratio showed a gradual increase with tumor progression. CONCLUSIONS: Our study demonstrates in a large series of patients that in advanced NSCLC there is an imbalance of the IL-2/IL-2 receptor system. Furthermore, circulating sIL-2R levels and the sIL-2R/IL-2 ratio may be useful as markers of disease activity and treatment response, suggesting a potential prognostic value.

Nonsustained ventricular tachycardia in ischemic heart disease: when and which pharmacological treatment?

Nonsustained ventricular tachycardia is not uncommon both in the presence and absence of organic heart disease and in the latter situation, is usually not associated with an increased risk. However, in patients with ischemic heart disease, especially in the post-infarction period, nonsustained ventricular tachycardia is associated with an increased risk of sudden, and possibly non-sudden, cardiac death. Several non-invasive and invasive tests have been utilized, individually or in combination, to risk stratify those patients. Left ventricular ejection fraction, the signal averaged electrocardiogram, and especially programmed ventricular stimulation have been commonly utilized to identify those patients at high risk for malignant tachyarrhythmias and to evaluate the potential benefit from antiarrhythmic treatment. At present, however, there is no consensus as to the best strategy to identify and treat high risk patients. Several ongoing multicenter clinical trials may eventually provide such guidelines. In the meantime, an algorithm for the management of those patients is suggested.

[Bronchoalveolar lavage in lower respiratory tract infections in patients with bronchopulmonary carcinoma. Our experience]. / Il lavaggio broncoalveolare nelle infezioni delle basse vie respiratorie nei pazienti con carcinoma broncopolmonare. Una nostra esperienza.

UNLABELLED: In order to evaluate the usefulness of the endoscopic procedures with BAL, we conducted a study on 92 patients with diagnosis of lung cancer, underwent to chemotherapy, identifying pathogenic species involved and the antibiotic sensibility and antibiotic resistance. Moreover, to evaluate possible modifications of alveolar cell population in neutropenic patients, we studied the specimens from BALs performed via fibreoptic bronchoscopy. METHODS: The cellular pattern of BALs in terms of concentration of total cells, concentrations of alveolar macrophages (AMs), of polymorphonucleates (PMNs) and lymphocytes (Ls) were compared in neutropenic and non-neutropenic patients. RESULTS: In the statistical analysis of our study we found a correlation, statistically significant, between patients with neutropenic episodes on the previous chemotherapy courses and incidence of LTRI. The mean concentrations x 100,000/ml of BAL fluid of total alveolar cells, AMs, PMNs and Ls were significantly lower, after chemotherapy, in group of neutropenic patients than in non neutropenic patients, respectively. CONCLUSIONS: In this study we found that during neutropenia the alveolar cell population was quantitatively deficient, confirming the hypothesis, proposed by other authors, of "lung aplasia" as a consequence or a concomitant event of chemotherapy-induced marrow toxicity.