Publications (13)101.11 Total impact
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Article: Weekly docetaxel vs. docetaxel-based combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer patients. The DISTAL-2 randomized trial.
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ABSTRACT: Doublet chemotherapy is more effective than single-agent as first line treatment of advanced non-small-cell lung cancer (NSCLC). No reliable information instead is available on the effect of doublets in second line treatment. The aim of DISTAL-2 study was to compare two doublets containing docetaxel with single agent docetaxel as second line treatment of patients with NSCLC (ClinicalTrials.gov id.:.NCT00345059). NSCLC patients, aged <75, PS 0-2, who had failed platinum-based chemotherapy, were randomly assigned with a 3:1:1 ratio to: arm A, weekly docetaxel (33.3mg/m(2) on days 1, 8, 15 q 4 weeks); arm B, weekly docetaxel (30 mg/m(2) on days 1, 8, 15) plus gemcitabine (800 mg/m(2) on days 1, 8 q 4 weeks) or plus vinorelbine (20mg/m(2) on days 1, 8 q 4 weeks) depending on which of the two had been used in first line; arm C, weekly docetaxel (as in arm B) plus capecitabine (625 mg/m(2) twice daily on days 5-18 q 4 weeks). Primary end-point was overall survival (OS). Two comparisons were planned: arm B vs. A and arm C vs. A. Overall, 375 patients had to be randomized. Response was assessed by RECIST, quality of life (QoL) by EORTC questionnaires. 84 patients were randomized from May 2005 to December 2006, when the trial was prematurely stopped due to the slow accrual. After 62 deaths, median OS was 40.0 weeks in arm A, 32.6 weeks in arm B (p=0.18 vs. A) and 39.7 weeks in arm C (p=0.90 vs. A). Response rate was 6.4, 16.7 and 5.3%, and median progression-free survival was 12.4, 13.1 and 11.9 weeks, for arms A, B and C, respectively. Patients in arm B had significantly more grade 3-4 haematological and non-haematological toxicity compared to arm A, and patients in arm C had significantly more grade 3-4 non-haematological toxicity compared to arm A. No relevant differences were found in QoL analysis, with the exception of significant worsening in appetite, vomiting and hemoptysis for patients in arm B. Due to early termination, the trial does not have the planned statistical power. However, available data do not support the role of docetaxel-based combination chemotherapy as second line in advanced NSCLC.Lung Cancer 02/2009; 63(2):251-8. · 3.43 Impact Factor -
Article: Incidence and clinical implications of venous thromboembolism in advanced colorectal cancer patients: the 'GISCAD-alternating schedule' study findings.
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ABSTRACT: To investigate the incidence and clinical implications of venous thromboembolism (VTE) in advanced colorectal cancer (ACC) patients treated and followed-up through a prospective randomised trial, comparing FOLFIRI chemotherapy given as an intermittent or as a continuous schedule. A total of 266 patients were randomised by 15 experimental centres: 168 (63.2%) were males, median age: 64.6 years, age range: 37-76 years. Almost all (95.5%) patients had metastatic disease, while the remainder were classified with locally advanced irresectable disease. For 138 (51.9%) of the patients, the chemotherapy treatment was intermittent FOLFIRI and the remaining patients received continuous treatment. All toxicities, including VTE, were prospectively collected. During the study protocol, the central data management gathered two cases of VTE. Our analysis retrieved 27 (10.2%) patients who developed a VTE, almost all (89%) during the course of chemotherapy treatment: 20 out of 27 during FOLFIRI, the remaining 7 during following lines or follow-up. VTE was the most frequent grade 3/4 toxicity. The incidence of VTE was significantly increased in the patients receiving continuous rather than intermittent treatment (HR 2.67, 95% CI 1.17-6.10; p<0.02). VTE is a common complication among advanced colorectal cancer patients and yet this type of toxicity is widely underestimated. In this randomised trial, VTE was the most frequent grade 3/4 toxicity. Use of an intermittent schedule is associated with a reduced risk of developing VTE.European journal of cancer (Oxford, England: 1990) 01/2009; 45(1):65-73. · 4.12 Impact Factor -
Article: Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial.
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ABSTRACT: Promising findings obtained using a weekly regimen of 5-fluorouracil (5-FU), epidoxorubicin, leucovorin (LV), and cisplatin (PELFw) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer (GISCAD) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients. From January 1998 to January 2003, 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion (stage pT3 N0) and/or lymph node metastasis (stage pT2 or pT3 N1, N2, or N3), were enrolled in a trial of adjuvant chemotherapies; 201 patients were randomly assigned to receive the PELFw regimen, consisting of eight weekly administrations of cisplatin (40 mg/m2), LV (250 mg/m2), epidoxorubicin (35 mg/m2), 5-FU (500 mg/m2), and glutathione (1.5 g/m2) with the support of filgrastim, and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU (375 mg/m2 daily) and LV (20 mg/m2 daily, 5-FU/LV). Disease-free and overall survival were estimated and compared between arms using hazard ratios (HRs) and Kaplan-Meier estimates. All statistical tests were two-sided. The 5-year survival rates were 52% in the PELFw arm and 50% in the 5-FU/LV arm. Compared with the 5-FU/LV regimen, the PELFw regimen did not reduce the risk of death (HR = 0.95, 95% confidence interval [CI] = 0.70 to 1.29) or relapse (HR = 0.98, 95% CI = 0.75 to 1.29). Less than 10% of patients in either arm experienced a grade 3 or 4 toxic episode. Neutropenia (occurring more often in the PELFw arm) and diarrhea and mucositis (more prevalent in the 5-FU/LV arm) were the most common serious side effects. Nevertheless, only 19 patients (9.4%) completed the treatment in the PELFw arm and 85 (43%) patients completed the treatment in the 5-FU/LV arm. Our study found no benefit from an intensive weekly chemotherapy in gastric cancer. The extent of toxicity experienced by the patients in the adjuvant setting suggests that, in gastric cancer, chemotherapy may be more safely administered preoperatively.CancerSpectrum Knowledge Environment 05/2007; 99(8):601-7. · 14.07 Impact Factor -
Article: Weekly paclitaxel, 5-fluorouracil and folinic acid with granulocyte colony-stimulating factor support in metastatic breast cancer patients: a phase II study.
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ABSTRACT: 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.Anti-Cancer Drugs 04/2006; 17(3):345-51. · 2.41 Impact Factor -
Article: Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study.
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ABSTRACT: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy. Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.Journal of Clinical Oncology 11/2005; 23(28):6865-72. · 18.37 Impact Factor -
Article: Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials.
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ABSTRACT: Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. We analysed data for 1265 patients who received chemotherapy (vinorelbine, gemcitabine, gemcitabine and vinorelbine, cisplatin and vinorelbine, or cisplatin and gemcitabine) within three randomised trials. Primary landmark analyses were restricted to 436 patients who received all six planned chemotherapy cycles and who were alive 180 days after randomisation. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1-2), or severe (grade 3-4). All statistical analyses were stratified by treatment allocation. Analyses were repeated in the out-of-landmark group (829 patients), stratifying by treatment allocation and number of chemotherapy cycles. The primary endpoint was overall survival. In the landmark group, hazard ratios of death were 0.65 (0.46-0.93) for patients with severe neutropenia and 0.74 (0.56-0.98) for those with mild neutropenia. Median survival after the landmark time of 180 days was 31.4 weeks (95% CI 25.7-39.6) for patients without neutropenia compared with 42.0 weeks (32.7-59.7) for patients with severe neutropenia, and with 43.7 weeks (36.6-66.0) for those with mild neutropenia (severe vs mild vs no neutropenia p=0.0118). Findings were much the same for the out-of-landmark group. Neutropenia during chemotherapy is associated with increased survival of patients with advanced non-small-cell lung cancer, and its absence might be a result of underdosing. Prospective trials are needed to assess whether drug dosing guided by the occurrence of toxic effects could improve efficacy of standard regimens.The Lancet Oncology 10/2005; 6(9):669-77. · 22.59 Impact Factor -
Article: Weekly docetaxel in pretreated metastatic breast cancer patients: a phase I-II study.
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ABSTRACT: We conducted a phase I-II study to determine the maximum tolerated dose (MTD), toxicity and activity of weekly docetaxel administration in pretreated metastatic breast cancer patients. In phase I, cohorts of 3 women with pretreated metastatic breast cancer were treated with a 1-hour infusion of docetaxelat 30, 35, 40 mg/m2/week after premedication with two doses of dexamethazone 8 mg 12 h apart. Subsequently, a cohort of 28 women was treated at the MTD for 24 consecutive weeks in a phase II setting and was assessed for toxicity and activity. Three patients were treated at each of the first two dose levels; 9 patients were treated at the 3rd level (40 mg/m2/week). Dose-limiting toxicities (DLTs) were experienced at that level by 2/6 patients of the first two accrued groups and in 2/3 patients of the 3rd (confirmation) group, thus establishing the subsequent phase II dose at 35 mg/m2/week. Two out of 28 evaluable patients (7.1%, 95% CI 0-16.7) showed complete responses, whereas 8 (28.6%, 95% CI 11.8-45.3) showed partial responses, and an objective response rate of 35.7% (95% confidence interval, CI 18-53.5%). In addition, 8 patients (28.6%) had stable disease. The median time to progression and overall survival were 5 (range 1-15) and 15 months (95% CI 7-23), respectively. One patient experienced 1 episode of grade 3 neutropenia. Severe asthenia was the main reason for interruption of chemotherapy (10 patients, 35.5%). In pretreated metastatic breast cancer patients, the sustained weekly administration of docetaxel, even though it demonstrated an activity similar to a 3-weekly schedule could not be maintained for the planned 24 weeks due to the progressive emergence of nonhematological side effects that approached DLTs.Oncology 02/2005; 68(4-6):356-63. · 2.27 Impact Factor -
Article: Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group.
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ABSTRACT: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient's quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity.Journal of Clinical Oncology 09/2003; 21(16):3025-34. · 18.37 Impact Factor -
Article: Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial.
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ABSTRACT: Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer (NSCLC). Some studies have also suggested that gemcitabine is well tolerated and effective in such patients. We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC. Patients aged 70 years and older, enrolled between December 1997 and November 2000, were randomly assigned to receive intravenous vinorelbine (30 mg/m(2) of body surface area), gemcitabine (1200 mg/m(2)), or vinorelbine (25 mg/m(2)) plus gemcitabine (1000 mg/m(2)). All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles. The primary endpoint was survival. Survival curves were drawn using the Kaplan-Meier method and analyzed by the Mantel-Haenszel test. Secondary endpoints were quality of life and toxicity. Of 698 patients available for intention-to-treat analysis, 233 were assigned to receive vinorelbine, 233 to gemcitabine, and 232 to vinorelbine plus gemcitabine. Compared with each single drug, the combination treatment did not improve survival. The hazard ratio of death for patients receiving the combination treatment was 1.17 (95% confidence interval [CI] = 0.95 to 1.44) that of patients receiving vinorelbine and 1.06 (95% CI = 0.86 to 1.29) that of patients receiving gemcitabine. Although quality of life was similar across the three treatment arms, the combination treatment was more toxic than the two drugs given singly. The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.JNCI Journal of the National Cancer Institute 04/2003; 95(5):362-72. · 13.76 Impact Factor -
Article: An interesting antitumor drug in the elderly patients over the age of 70: weekly docetaxel.
Tumori 88(1 Suppl 1):S41-3. · 0.86 Impact Factor -
Article: Adjuvant Treatment of High-Risk, Radically Resected Gastric Cancer Patients With 5-Fluorouracil, Leucovorin, Cisplatin, and Epidoxorubicin in a Randomized Controlled Trial
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ABSTRACT: Background Promising findings obtained using a weekly regimen of 5-fluorouracil (5-FU), epidoxorubicin, leucovorin (LV), and cisplatin (PELFw) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer (GISCAD) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients. Methods From January 1998 to January 2003, 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion (stage pT3 N0) and/or lymph node metastasis (stage pT2 or pT3 N1, N2, or N3), were enrolled in a trial of adjuvant chemotherapies; 201 patients were randomly assigned to receive the PELFw regimen, consisting of eight weekly administrations of cisplatin (40 mg/m2), LV (250 mg/m2), epidoxorubicin (35 mg/m2), 5-FU (500 mg/m2), and glutathione (1.5 g/m2) with the support of filgrastim, and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU (375 mg/m2 daily) and LV (20 mg/m2 daily, 5-FU/LV). Disease-free and overall survival were estimated and compared between arms using hazard ratios (HRs) and Kaplan–Meier estimates. All statistical tests were two-sided. Results The 5-year survival rates were 52% in the PELFw arm and 50% in the 5-FU/LV arm. Compared with the 5-FU/LV regimen, the PELFw regimen did not reduce the risk of death (HR = 0.95, 95% confidence interval [CI] = 0.70 to 1.29) or relapse (HR = 0.98, 95% CI = 0.75 to 1.29). Less than 10% of patients in either arm experienced a grade 3 or 4 toxic episode. Neutropenia (occurring more often in the PELFw arm) and diarrhea and mucositis (more prevalent in the 5-FU/LV arm) were the most common serious side effects. Nevertheless, only 19 patients (9.4%) completed the treatment in the PELFw arm and 85 (43%) patients completed the treatment in the 5-FU/LV arm. Conclusions Our study found no benefit from an intensive weekly chemotherapy in gastric cancer. The extent of toxicity experienced by the patients in the adjuvant setting suggests that, in gastric cancer, chemotherapy may be more safely administered preoperatively. -
Article: Response: Re: Adjuvant Treatment of High-Risk, Radically Resected Gastric Cancer Patients with 5-Fluorouracil, Leucovorin, Cisplatin, and Epidoxorubicin in a Randomized Controlled Trial
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Article: [The dilemma of first-line chemotherapy in advanced non-small-cell lung cancer: are third-generation drugs all the same?].
Tumori 94(3):5-14. · 0.86 Impact Factor
