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Edmondo Terzoli

Publications and source records attributed to Edmondo Terzoli.

At least 19 recordsLinked to original sources
PubMed2007

Troponin-T and myoglobin plus echocardiographic evaluation for monitoring early cardiotoxicity of weekly epirubicin-paclitaxel in metastatic breast cancer patients.

Increased serum level of troponin-T and myoglobin has been recently reported to be related to cumulative anthracycline exposure. Left ventricular ejection fraction seems accurate in monitoring systolic function according to the latest version of Toxicity Criteria by chemotherapeutics 3.0. From January 2002, 20 patients with untreated advanced breast cancer received epirubicin (25 mg/m/week) and paclitaxel (80 mg/m/week) for 24 weeks. Troponin-T, myoglobin and biochemical serum enzymes circulating levels were measured immediately before and 4 h after epirubicin administration every week. Patients underwent electrocardiography and echocardiography at weeks 0, 8, 16 and 24. The number of courses administered was 352 (median 18, range 4-24). Epirubicin median dose administered was 600 mg/m and paclitaxel median dose administered was 1760 mg/m. Troponin-T never overcame the upper normal limit; one patient experienced troponin-T elevation without any clinical or instrumental sign of cardiac failure. Myoglobin never significantly increased with the exception of a patient who underwent several abdominal fluid drainages. Creatine kinase MB and C-reactive protein never moved outside the upper normal limit. No symptomatic cardiac event was recorded. In 55 performed echocardiograms at weeks 0, 8, 16 and 24, neither left ventricular ejection fraction nor early peak flow/atrial flow velocity registered any significant decrease. No troponin-T or myoglobin serum elevations and Left ventricular ejection fraction/early peak flow/atrial flow velocity changes were registered in our series of nonsymptomatic women during epirubicin/paclitaxel weekly chemotherapy in the absence of clinical cardiac toxicity. Longer follow-up is needed, however, to understand whether the troponin-T or myoglobin circulating level measurement is able to detect subclinical, early-stage doxorubicin-induced cardiotoxicity.

Aged↗
PubMed2006

Weekly docetaxel as second line chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials.

BACKGROUND: Docetaxel has to be considered as the reference control arm for second line chemotherapy for advanced NSCLC. Weekly docetaxel has been compared to standard 3-weekly schedule in a randomized fashion to determine if such schedule improves survival and quality of life. We performed a literature-based meta-analysis of all randomized clinical trials (RCTs) comparing weekly over 3-weekly docetaxel in advanced NSCLC. METHODS: All randomized trials were considered eligible. A literature-based meta-analysis was accomplished, and event-based relative risk ratios (RR) with 95% confidence interval (CI) were derived. A fixed- and a random-effect model according to the inverse variance and the Mantel-Haenszel method were applied. Heterogeneity test was applied as well. RESULTS: We found six RCTs (three phase III, two phase II, 1018 patients), in which data for overall survival (OS), overall response rate (ORR) and grade 3-4 (G3-4) WHO neutropenia were available. When considering only phase III RCTs, OS did not significantly differ between the two arms (RR 1.01, 95% CI 0.76, 1.42, p=0.785) with no significant heterogeneity (p=0.42). Regarding activity, no significant differences in favour of weekly docetaxel were found, although a trend for 3-weekly schedule was observed (RR 0.81, 95% CI 0.47, 1.40, p=0.485), with no significant heterogeneity (p=0.27). No differences were found in the overall population also considering the phase II trials. Regarding G3-4 neutropenia, a significant homogenous advantage in favour of weekly docetaxel was found, with an absolute benefit of 15-19%. CONCLUSIONS: Although considering all drawbacks related to literature-based meta-analyses, weekly docetaxel seems not to improve survival when compared to 3-weekly docetaxel. The significant benefit in grade 3-4 neutropenia seems to suggest this approach in patients with NSCLC pretreated for advanced disease. The quality of life of both schedules needs to be evaluated in an individual patient data meta-analysis.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Persistence of high-dose oxaliplatin-induced neuropathy at long-term follow-up.

Oxaliplatin (L-OHP) has become a standard treatment for advanced colorectal cancer and a valid option for patients in the adjuvant setting. Compared with cisplatin, L-OHP has no renal toxicity, only mild hematological and gastrointestinal toxicity, while neurotoxicity is the limiting toxicity. This side effect has been described as a transient distal dysesthesia, enhanced by exposure to cold, and as a dose-related cumulative mild sensitive neuropathy. We studied two groups of patients (18 and 13) with advanced colorectal cancer, treated with median cumulative doses of L-OHP 862 mg/m2 and 1,033.5 mg/m2. All the patients had been evaluated previously, during treatment, after discontinuation and after a long follow-up of 5 years to verify the incidence and the characteristics of the neuropathy induced by this antineoplastic agent. The clinical and neurophysiological examinations showed an acute and transient neurotoxicity and a cumulative dose-related sensory neuropathy in nearly all the patients. The reversibility of these effects was studied. Five patients continue to manifest symptoms and signs of neurotoxicity after a long follow-up, indicating persistence of this peculiar type of neuropathy.

Action Potentials↗
PubMed2006

Early switch with aromatase inhibitors as adjuvant hormonal therapy for postmenopausal breast cancer: pooled-analysis of 8794 patients.

BACKGROUND: The magnitude of the survival benefit of aromatase inhibitors (AIs) after 2-3 years of tamoxifen as adjuvant hormonal therapy for early breast cancer is still unclear. We performed a literature-based meta-analysis, to look how much advantages adjuvant the "early switch" strategy add over standard tamoxifen for 5 years. METHODS: A pooled analysis of all phase-III trials was accomplished, and event-based relative risk ratios (RR) with 95% confidence interval (CI) were derived. Significant differences in primary outcome (EFS and RFS, event- and relapse-free survival), and secondary outcomes (OS, overall survival, deaths without progression, other cancers and toxicities), were explored. Magnitude outcome measures were absolute benefits and number of patients needed to treat. Heterogeneity test was applied as well. RESULTS: Five trials (8794 patients) were gathered. The risk of any event is reduced with AIs of 23%, with an absolute benefit of 3.8% (RR 0.67, 95% CI 0.59, 0.76). Again, RFS (RR 0.68, 95% CI 0.59, 0.79) or both LRFS and DFRS, were significantly improved with AIs. OS was significantly prolonged with AIs, with an absolute benefit of 1.2% (RR 0.76, 95% CI 0.62, 0.93), without significant heterogeneity. Bone fractures were significantly higher in patients receiving AIs (RR 1.50, 95% CI 1.12, 2.02), and endometrial cancer in patients who continued to receive tamoxifen (RR 0.32, 95% CI 0.13, 0.77), without significant heterogeneity. CONCLUSIONS: The early switch strategy improves survival over standard tamoxifen for 5 years, with a different toxicity profile. The lack of significant heterogeneity in the analysis underscores the homogenous effect across all trials.

Aged↗
PubMed2006

Does granulocyte colony-stimulating factor worsen anemia in early breast cancer patients treated with epirubicin and cyclophosphamide?

PURPOSE: We report on the effects of granulocyte colony-stimulating factor (G-CSF) on hemoglobin (Hb) value in early breast cancer patients receiving high-dose epirubicin and cyclophosphamide (EC) adjuvant treatment. METHODS: Five hundred and six stage I or stage II female breast cancer patients were treated with E 120 mg/m2 and C 600 mg/m2 with or without G-CSF and randomly assigned to receive in a factorial 2 x 2 design: EC; EC + lonidamine; EC + G-CSF; EC + lonidamine + G-CSF. Five consecutive G-CSF schedules tested 100 randomly assigned patients each: (1) 480 microg subcutaneously on days 8 to 14; (2) 480 microg on days 8, 10, 12, 14; (3) 300 microg on days 8 to 14; (4) 300 microg on days 8, 10, 12, and 14; and (5) 300 microg on days 8 and 12. The mean Hb level of 246 patients receiving EC plus G-CSF was compared with that of 240 patients receiving EC alone. The data presented are derived from an exploratory hypothesis-generating analysis. RESULTS: The EC dose intensity did not statistically differ between the G-CSF and the control arm. From the third cycle onward, the mean Hb value resulted significantly lower in G-CSF arm compared with control at each time point of each cycle (P < .0001). No statistically significant difference in the mean Hb level was observed between schedule 5 and control. Of interest, from the second course onward, the mean Hb level tended to be lower in patients receiving seven or four G-CSF injections compared with those patients who received only two injections. CONCLUSION: Our data suggest that a G-CSF dose-related effect may play a role in worsening anemia in patients receiving adjuvant EC.

Anemia↗
PubMed2006

Benefit of taxanes as adjuvant chemotherapy for early breast cancer: pooled analysis of 15,500 patients.

BACKGROUND: The magnitude of the survival benefit of taxanes as adjuvant chemotherapy for early breast cancer is still unclear. A pooled analysis of Phase III trials was performed to assess the advantages that adjuvant taxane chemotherapy has over standard chemotherapy. METHODS: All Phase III trials were considered eligible. A pooled analysis was accomplished and event-based relative risk ratios (RR) with 95% confidence intervals (95% CI) were derived. The significant differences in disease-free survival (DFS) and overall survival (OS) were explored. Magnitude outcome measures were absolute benefits and the number of patients needed to treat. A heterogeneity test was applied as well. A sensitivity analysis in 6 subpopulations was also performed. RESULTS: Nine trials designed to assess if paclitaxel or docetaxel improve survival (15,598 patients) were gathered. One of the 9 trials did not report OS results. Significant differences in favor of taxanes were seen in DFS in the overall (RR: 0.86; 95% CI, 0.81-0.90 [P<.00001]) and lymph node-positive population (RR: 0.84; 95% CI, 0.79-0.89 [P<.0001]), and in OS in the overall (RR: 0.87; 95% CI, 0.81-0.83 [P<.0001]) and lymph node-positive population (RR: 0.84; 95% CI, 0.77-0.92 [P<.0001]). The absolute benefits in DFS and OS in favor of taxanes ranged from 3.3% to 4.6% and from 2.0% to 2.8%, respectively. CONCLUSIONS: Considering all the available Phase III trials, taxane-based adjuvant chemotherapy for early breast cancer seems to add a significant benefit in both DFS and OS over standard chemotherapy. The lack of significant heterogeneity in the sensitivity analysis underscores the homogeneous effect across all trials.

Antineoplastic Agents, Phytogenic↗
PubMed2006

A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer.

BACKGROUND: Many emerging new drugs have recently been trialled for treatment of early and advanced breast cancer. Among these new agents paclitaxel and gemcitabine play a crucial role, mostly in patients with relapsed and metastatic disease after failure of chemotherapy with antracyclines. METHODS: A phase II study was started in order to evaluate the activity and toxicity of a combination of paclitaxel and gemcitabine in a biweekly schedule on metastatic breast cancer patients previously treated with antracyclines. RESULTS: Twenty-five patients received paclitaxel (150 mg/mq) by 3-hours infusion, followed by gemcitabine (2000 mg/mq) given as a 60 min i.v. infusion (day 1-14) for a maximum of eight cycles. In all patients treatment was evaluated for toxicity and efficacy; four patients (16%) achieved a complete response, 12 (48%) a partial response giving an overall objective response rate of 64%. Stable disease was documented in 5 patients (20%) and progressive disease occurred in 4 patients (16%). CONCLUSION: The schedule of treatment was safe and tolerable from a haematological and non-haematological point of view. These data confirm that the combination of gemcitabine and paclitaxel on a biweekly basis is an effective and well-tolerated regimen in breast cancer patients with prior therapeutic exposure to antracyclines.

Adult↗
PubMed2006

An integrated psychological strategy for advanced colorectal cancer patients.

BACKGROUND: There is evidence regarding the usefulness of psychosocial intervention to improve health related quality of life (HRQOL) in adult cancer patients. The aim of this report is to describe an integrated approach and to evaluate its feasibility in routine clinical practice in 98 advanced colorectal cancer (ACC) patients during chronomodulated chemotherapy. METHODS: A prospective non-randomised design was developed and applied in a cancer out-patient setting. The intervention consisted of an integrated approach, whereby the psycho-oncologist had an active role in the health care team with the physician and routinely included psychological understanding in the medical treatment program. The psychological evaluation assessed: a) adaptation, awareness, psychopathological disorders through a psychodynamic interview; b) anxiety and depression using the HAD scale; c) subjective perception of care quality through a structured interview and d) HRQOL evaluation assessment with the EORTC QLQ C30. Outcomes data were collected before and after 18 weeks of chemotherapy. RESULTS: After 18 weeks of chemotherapy a significant improvement of adaptation and awareness was observed. The HADs results showed a significant decrease in anxiety when compared to pre-treatment. The structured interview showed a significant increase of patients who positively experienced the impact of medical treatment on HRQOL, anxiety, depression, interpersonal relationships, free-time and who positively experienced the care quality. Indeed, a majority of patients positively experienced the team relationship modality during the whole treatment. All scales on the EORTC questionnaire remained unchanged during the entire treatment. CONCLUSION: Our results suggest that it is feasible to carry out an integrated approach during chemotherapy. These results seem to support the integrated approach as a tool in aiding advanced colorectal cancer patients' ability to cope with their diagnosis and treatment although an appropriately designed study is required to confirm this.

Adaptation, Psychological↗
PubMed2006

Randomised phase II study of standard versus chronomodulated CPT-11 plus chronomodulated 5-fluorouracil and folinic acid in advanced colorectal cancer patients.

In this study, a randomised phase II trial explored the effects of 6-h chronomodulated CPT-11 infusion in advanced colorectal cancer patients. Sixty-eight pre-treated patients were randomly assigned to CPT-11 administered at 180 mg/m2 on day 1, by 1-h infusion (Arm A) or 6-h sinusoidal infusion with peak timing at 5:00 a.m. (Arm B). All patients also received chronomodulated folinic acid/5-fluorouracil (FA/5-FU). Patients in Arm B obtained a 25.7% response rate for 7.0 months duration, a progression-free survival for 8.0 months and a median survival of 28 months. The same data in Arm A were 18.2%, 4.5, 6.0 and 18 months, respectively. No differences in drugs dose-intensity or increased toxicity with prolonged chronomodulated infusion were detected. Major grade 3-4 toxicity was diarrhoea: 10 patients in Arm A and 13 in Arm B. In conclusion, this study has shown that chronomodulated infusion of CPT-11 and FA/5-FU is safe, active and can be integrated with oxaliplatin (EORTC 05011) for the treatment of advanced colorectal cancer.

Adenocarcinoma↗
PubMed2006

Weekly paclitaxel, 5-fluorouracil and folinic acid with granulocyte colony-stimulating factor support in metastatic breast cancer patients: a phase II study.

We conducted a phase II study to determine the activity and tolerability of weekly paclitaxel, 5-fluorouracil (5-FU) and folinic acid plus granulocyte colony-stimulating factor (G-CSF) support in anthracycline-pre-treated or -resistant metastatic breast cancer patients. The phase II study was designed following the Simon optimal-two stage method. Patients received paclitaxel 80 mg/m, folinic acid 10 mg/m and bolus infusion of 5-FU 300 mg/m every week plus G-CSF on day 3 for 24 consecutive weeks in the absence of disease progression. From May 1998 to May 2000, 51 patients entered the study. Patients received a median relative dose intensity of 97.5% (range 81-100%). No severe toxicities were observed. Seven patients (14%) experienced neutropenia grade 2. Seven patients (14%) experienced grade 2 anemia. Two patients (4%) experienced severe asthenia. Three out of 50 evaluable patients [6%, 95% confidence interval (CI) 2-12.6%] showed a complete response, whereas 23 (46%, 95% CI 32.2-59.8%) had a partial response, with an overall response rate of 52% (95% CI 38.2-65.8%). In addition, eight patients (15.7%) had stable disease. In the 13 patients untreated for metastatic disease, the overall response rate was 92.3% (CI 77.8-100), with one complete response and 11 partial responses (84.6% CI 65-100%). In the whole group, the median time to progression and overall survival were 8 (range 1-18) and 14 months (95% CI 11-17), respectively. Thus, in metastatic breast cancer patients pre-treated with anthracyclines, the weekly administration of paclitaxel, 5-FU and folinic acid with G-CSF support seems to be extremely tolerable and active.

Adult↗
PubMed2006

Ten years of experience with weekly chemotherapy in metastatic breast cancer patients: multivariate analysis of prognostic factors.

Weekly chemotherapy administration represents an emerging option for the treatment of metastatic breast cancer. In order to identify clinical and biological prognostic factors for outcome, we performed a multivariate analysis in a 10-year experience of weekly chemotherapy for metastatic breast cancer patients. The original databases of phase II trials of metastatic breast cancer patients who had undergone first-line weekly chemotherapy were collected. Clinical and biological covariables were screened for a possible relationship with time to progression and overall survival in a Cox model. From 1990 to 2003, 184 patients were enrolled in three consecutive phase II studies, to evaluate activity and tolerability of weekly epirubicin with lonidamine or vinorelbine or paclitaxel. All patients were evaluable for clinical variables; histological samples were available in 40 patients. At a median follow-up of 24 months, median time to progression was 9 months (95% confidence interval 8-10) and median overall survival was 34 months (95% confidence interval 24-42). Independent variables were response (hazard ratio 2.34, P<0.0001), receptor status (hazard ratio 1.62, P=0.01) and performance status (hazard ratio 2.31, P<0.0001) for time to progression, and response (hazard ratio 1.86, P=0.005), performance status (hazard ratio 2.81, P<0.0001), dominant metastatic site (hazard ratio 2.27, P<0.0001) and enrollment period (hazard ratio 2.51, P=0.001) for overall survival. Although no biological factors were entered into the Cox model owing to the small sample size, some subpopulations showed a negative trend in survival. In our series of patients who had undergone weekly chemotherapy for metastatic breast cancer, independent prognostic factors for survival improvement were responders, performance status 0-1, nonvisceral dominant metastatic site and enrollment period. A greater sample population is needed to extensively screen for biological prognostic factors.

Adolescent↗
PubMed2006

Is recurrent venous thromboembolism after therapy reduced by low-molecular-weight heparin compared with oral anticoagulants?

PURPOSES: To evaluate whether the incidence of recurrent venous thromboembolism (VTE) events after therapy differs for patients treated with long-term low-molecular-weight heparin (LMWH) or oral anticoagulant therapy (OAT). METHODS: All randomized studies were searched through computerized queries of MEDLINE, the Cochrane Controlled Trials Register, the American Society of Hematology abstract database, and the American Society of Clinical Oncology abstract database. RESULTS: Eleven studies including 2,907 patients were identified. Seven studies evaluated a period of 3 to 9 months after cessation of the allocated treatment: 5.4% of patients in the LMWH group vs 4% in the arm allocated to OAT had an episode of recurrent symptomatic VTE. Combined analysis showed a nonsignificant trend in lowering recurrent symptomatic VTE in favor of OAT (relative risk [RR], 1.29; 95% confidence interval [CI], 0.82 to 2.02; p = 0.27). By contrast, during active treatment, a statistically significant reduction of the risk of recurrent symptomatic VTE in favor of LMWH over OAT was registered (RR, 0.63; 95% CI, 0.47 to 0.83; p = 0.001). Regarding cancer patients only, 37 of 569 patients (6.5%) in the LMWH group had recurrent symptomatic VTE vs 69 of 546 patients (12.6%) in the OAT group, with a statistically significant reduction of the risk of recurrent symptomatic VTE in favor of LMWH (RR, 0.52; 95% CI, 0.35 to 0.76; p = 0.001). CONCLUSIONS: Despite the significant reduction of the risk of recurrent symptomatic VTE in favor of LMWH over OAT during treatment, patients treated with long-term LMWH do not seem to have more frequently recurrent VTE events compared with OAT after cessation of therapy. The significant difference favoring LMWH over OAT among all patients receiving treatment comes mostly from studies enrolling cancer patients.

Anticoagulants↗
PubMed2005

New aromatase inhibitors as second-line endocrine therapy in postmenopausal patients with metastatic breast carcinoma: a pooled analysis of the randomized trials.

BACKGROUND: New aromatase inhibitors (AI) (second-generation: formestane and fadrozole; third-generation: letrozole, anastrozole, vorozole, and exemestane) have been tested in several controlled clinical trials after tamoxifen failure in metastatic breast carcinoma (MBC). They have resulted in better survival compared with megestrol acetate (MEG) in a number of studies. The authors performed a pooled analysis including all the Phase III trials published between 1996 and 2004 evaluating the AIs approved or not by the Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medical Products (EMEA) as second-line endocrine therapy (ET) for patients with MBC. METHODS: The overall response rate (ORR) and time to disease progression (TTP) were considered the primary end points, whereas toxicity was regarded as a secondary objective. Relative risk, 95% confidence interval, and heterogeneity were derived using 2 methods. RESULTS: No significant differences in ORR and TTP were noted in the entire group of 9 trials comparing AI with MEG (3908 patients) and in the 6 trials comparing nonsteroidal AI and MEG (2415 patients). AI yielded significantly more hot flashes than MEG (P = 0.004) but caused significantly less toxicity than MEG in weight gain (P = 0.001), dyspnea (P = 0.008), and peripheral edema (P = 0.03). Significant heterogeneity for nausea, weight gain, dyspnea, and peripheral edema was registered. When steroidal AIs were excluded from the toxicity analysis, nausea maintained its strongly significant heterogeneity (P = 0.0002), whereas weight gain, dyspnea, and peripheral edema lost their significance. CONCLUSIONS: This pooled analysis suggested that AIs in second-line ET for patients with MBC do not seem to add any significant benefit to MEG in terms of ORR and TTP. With regard to toxicity, the findings in the current study showed that weight gain, dyspnea, and peripheral edema are more frequent with the use of MEG, whereas hot flashes were more represented using AI.

Aged↗