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Biomedical subjects

G V Scagliotti

Publications and source records attributed to G V Scagliotti.

At least 19 recordsLinked to original sources
PubMed2006

ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine.

BACKGROUND: Pivotal studies indicate a role of excision repair cross-complementation 1 (ERCC1) gene and ribonucleotide reductase M1 (RRM1) gene in conferring a differential sensitivity to cytotoxic chemotherapy and epidermal growth factor receptor (EGFR) gene has been recently extensively investigated in non-small-cell lung cancer (NSCLC). DESIGN: Formalin-fixed, paraffin-embedded bronchoscopic/fine needle aspiration biopsies obtained from 70 patients with advanced NSCLC were retrospectively collected to investigate the expression level of ERCC1, RRM1 and EGFR by real-time PCR. Sufficient amounts of messenger RNA (mRNA) were successfully extracted from 61 (87%) specimens, reverse transcribed and amplified with intron-spanning primers. Forty-one patients had stage IV disease and 43 received cisplatin/gemcitabine chemotherapy. RESULTS: A strong correlation between ERCC1 and RRM1 mRNA levels (r(s) = 0.624, P < 0.0001) was found. Median survival time in patients with low ERCC1 was significantly longer (17.3 versus 10.9, P = 0.0032 log-rank test) as well as in patients with low RRM1 (13.9 versus 10.9, P = 0.0390 log-rank test). Concomitant low expression levels of ERCC1 and RRM1 (n = 33) were predictive of a better outcome (14.9 versus 10.0, P = 0.0345 log-rank test). Among cisplatin-treated patients, a low ERCC1 level was highly predictive of a longer survival (23.0 versus 12.4, P = 0.0001 log-rank test). No correlation between gene expression levels and histology was reported. No significant correlation between EGFR expression level and survival was found. At multivariate analysis, performance status, response to chemotherapy, presence of weight loss and ERCC1 were independent prognostic factors for survival. CONCLUSIONS: This retrospective study further validates ERCC1 and RRM1 genes as reliable candidates for customized chemotherapy and shows a higher impact on the survival of NSCLC patients treated with cisplatin/gemcitabine for ERCC1. Prospective pharmacogenomic studies represent a research priority in early and advanced NSCLC.

Adult↗
PubMed2006

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer.

This trial aimed to assess the feasibility and tumour control of concurrent chemoradiotherapy or radiotherapy alone after docetaxel-based induction chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy with docetaxel (85 mg m(-2), day 1) plus cisplatin (40 mg m(-2), days 1 and 2). Patients without disease progression on day 43 were randomised to radiotherapy (2 Gy for 5 days week(-1); total 60 Gy) alone or with docetaxel 20 mg m(-2) once weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104 were evaluable for response. After induction chemotherapy, the overall response rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were subsequently randomised to local treatment. After randomised therapy, the ORR was 53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and 14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities during induction chemotherapy and randomised therapy were grades 3-4 neutropenia and grade 3 lymphocytopenia, respectively. Docetaxel-cisplatin induction therapy followed by concurrent docetaxel and thoracic radiotherapy is a feasible treatment option, showing good clinical activity and tolerability, for locally advanced NSCLC.

Adolescent↗
PubMed2006

A randomized phase II trial evaluating standard (50 mg/min) versus low (10 mg/min) infusion duration of gemcitabine as first-line treatment in advanced non-small-cell lung cancer patients who are not eligible for platinum-based chemotherapy.

PURPOSE: Gemcitabine is one of the most active drugs against non-small-cell lung cancer (NSCLC). Preclinical data suggested that gemcitabine efficacy could be improved by increasing the dose or by increasing the infusion duration. This study has been designed in order to explore two different approaches of gemcitabine dose intensification in patients with advanced NSCLC. PATIENTS AND METHODS: A total of 121 chemonaive patients with locally advanced or metastatic NSCLC not suitable for a platinum-based chemotherapy were randomly allocated to chemotherapy with gemcitabine 1500 mg/m2 on days 1 and 8 every 3 weeks by standard 30 min intravenous infusion (arm A), or gemcitabine 10 mg/m2/min for 150 min on days 1 and 8 every 3 weeks by intravenous infusion at fixed dose rate (arm B). RESULTS: One hundred and seventeen patients were fully analyzed. No difference in response rate (16.1% versus 9.9%, p=0.28), median time to disease progression (4 months versus 4.5 months, p=0.34) median survival (9.8 months in both arms), and 1-year survival (42.6% versus 39.0% p=0.98) was detected in arms A and B, respectively. No treatment-related deaths occurred. Main hematological toxicities were grade 3-4 neutropenia observed in 17.9% of patients in group A and in 49.2% of individuals in group B (p=0.0002). The incidence of febrile neutropenia was 3.3% in arm A and 0% in arm B (p=0.17). Grade 3-4 thrombocytopenia was more frequently observed in arm B patients (9.9% versus 1.8%, p=0.057). Non-hematological toxicity was similar in both arms, and consisted in grade 1-2 gastrointestinal toxicity observed in 48.2% of patients in arm A and 41.0% in arm B. CONCLUSION: Intensification of standard doses or prolonged infusion schedule did not result in efficacy improvement. Gemcitabine infusion duration does not warrant further investigation in patients with advanced NSCLC.

Aged↗
PubMed2006

Prevalence of adrenal incidentaloma in a contemporary computerized tomography series.

Adrenal incidentalomas, defined as masses discovered incidentally during imaging investigation of non-adrenal disorders, have become a rather common finding in clinical practice. The prevalence is not well characterized and varies among studies. The aim of the present study was to perform a prospective evaluation of the prevalence of adrenal incidentalomas among subjects undergoing computerized tomography (CT) scan of the chest in a screening program of lung cancer (Tic TAC study) in Piedmont, a region of Northwestern Italy. This evaluation included 520 subjects (382 males and 138 females, aged between 55-82 yr), referred to our hospital from April to December 2001. Twenty-three patients with adrenal masses were identified: 21 adrenal adenomas, 1 myelolipoma, and 1 metastasis of lung cancer. Therefore, the overall prevalence of adrenal lesions was 4.4%, and that of benign adrenal masses was 4.2%. This prevalence is higher than those found in previous CT scan series reported in the literature, probably because of the use of high-resolution CT scanning technology. Another factor that influenced our results is that subject age is skewed towards the decades characterized by a greater occurrence of adrenal masses. The outcome of this study confirms that we are presently able to identify incidentally discovered adrenal masses more often than in early years and that the prevalence of adrenal incidentalomas on CT images is approaching that of autopsy series. The present study provides a reliable estimate of the prevalence of adrenal incidentaloma with currently used CT scanners. Notwithstanding that our subjects were at increased risk of lung cancer, the rate of adrenal metastases was low. We think that the present results can be generalized even if we may disclose the lack of histological diagnosis.

Adrenal Gland Neoplasms↗
PubMed2006

Treatment of advanced non-small cell lung cancer.

In the last decade the treatment of advanced-metastatic non-small cell lung cancer has substantially improved. If in the early 90s there was still concern about the real efficacy of chemotherapy over best suppotive care alone in the advanced setting, constant developments in clinical research have demonstrated the survival advantage of active anti-cancer drugs not only in the first-line setting, but, lately, even in patients with recurrent disease after failure of two previous chemotherapy lines. With the premises of high throughput technologies, translational research is aiming to characterize patients and tumors on a molecular basis. With pharmacogenomics it would then be possible to accurately predict patient outcome and tailor the treatment strategy according to the geno-phenotype of single patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Phase II study of gemcitabine plus oxaliplatin as first-line chemotherapy for advanced non-small-cell lung cancer.

This phase II study evaluated the response rate and tolerability of gemcitabine-oxaliplatin chemotherapy in non-small-cell lung cancer (NSCLC) patients. Chemonaive patients with stage IIIB or IV NSCLC received gemcitabine 1000 mg m(-2) on days 1 and 8, followed by oxaliplatin 130 mg m(-2) on day 1. Cycles were repeated every 21 days for up to six cycles. From February 2002 to May 2004, 60 patients were enrolled into the study in seven Italian institutions. We observed one complete response (1.7%) and 14 partial responses (23.3%), for an overall response rate of 25.0% (95% confidence interval, 14.7-37.9%). The median duration of response was 5.9 months (range 1.5-17.1 months). With a median follow-up of 6.7 months, median time to progressive disease and overall survival were 2.7 (range 1.9-3.4 months) and 7.3 months (range 7.2-8.6 months), respectively. The main grade 3-4 haematological toxicities were transient neutropenia in 11.7% and thrombocytopenia in 8.3% of the patients. Nausea/vomiting was the main grade 3-4 nonhaematological toxicity, occurring in 10.0% of the patients. Two (3.3%) patients developed grade 3 neurotoxicity. Our results show that gemcitabine-oxaliplatin chemotherapy is active and well tolerated in patients with advanced NSCLC, deserving further study, especially for patients not eligible to receive cisplatin.

Adult↗
PubMed2005

Three-year findings of an early lung cancer detection feasibility study with low-dose spiral computed tomography in heavy smokers.

BACKGROUND: Low-dose spiral computed tomography (sCT) showed a four-fold increase in the detection rate in high-risk subjects and a higher percentage of stage I lung cancer in comparison with chest X-ray. However, there is a considerable discrepancy among studies in the percentage of lung nodules, overall lung cancer and stage I detection rate. SUBJECTS AND METHODS: From April to December 2001, 520 asymptomatic volunteers aged >or=55 years with a history of cigarette smoking >or=20 pack-years and no previous cancer were enrolled to receive an annual sCT of the chest for five consecutive years. RESULTS: Seventy three per cent were male, median age was 59 years and 91% were current smokers. At baseline, nodules >or=5 mm were detected in 114 (22%) undergoing sCT; the size of lung nodules ranged from 5 to 9.9 mm in 81.5% of the cases. Five (1%) cases of lung cancer were detected. In two additional cases a pathological diagnosis of atypical adenomatous hyperplasia was made. Three new cases of lung cancer were detected in the second and third year of the study. One interval case was detected during the third year. CONCLUSIONS: Despite some promising data, convincing evidence from ongoing randomized trials is needed to support the routine use of sCT as a recommended tool for screening of lung cancer.

Aged↗
PubMed2005

Cost-minimisation analysis comparing gemcitabine/cisplatin, paclitaxel/carboplatin and vinorelbine/cisplatin in the treatment of advanced non-small cell lung cancer in Italy.

A retrospective cost-minimisation analysis was conducted comparing novel chemotherapies for the treatment of chemo-naive patients with locally advanced, recurrent, and/or metastatic non-small cell lung cancer (NSCLC). Resource use information was obtained from a Phase III randomised trial investigating the efficacy and toxicity of gemcitabine/cisplatin (Gem/Cis), paclitaxel/carboplatin (Pac/Carbo) and vinorelbine/cisplatin (Vin/Cis) combination regimens in 612 patients with advanced NSCLC. Since there were no statistically significant differences between the three treatments in terms of progression-free or overall survival in this trial, a cost-minimisation analysis was considered to be the appropriate type of economic evaluation. The perspective was that of the national healthcare provider in Italy. Medical resource use was obtained from the clinical trial database, from which mean cost streams were calculated for each treatment group. The mean total treatment costs per patient were 8094 euros, 11,203 euros and 9320 euros for the Gem/Cis, Pac/Carbo and Vin/Cis regimens, respectively. Based on resource consumption in a clinical trial, Gem/Cis had the lowest overall mean costs of the three chemotherapy regimens. Gem/Cis therefore has the potential to save costs in the treatment of advanced NSCLC in Italy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Pemetrexed: a new cytotoxic agent in the development for first-line non-small-cell lung cancer.

Pemetrexed is a new cytotoxic agent that is a standard of care for the second-line treatment of non-small-cell lung cancer (NSCLC) and treatment of malignant pleural mesothelioma. It is currently in clinical development for the first-line treatment of NSCLC. In untreated advanced NSCLC, single-agent activity has been demonstrated in phase II trials. Pemetrexed has encouraging response rates and a favorable toxicity profile. Pemetrexed also has promising activity and acceptable toxicity when combined with platinum compounds or gemcitabine. Dietary supplementation with low-dose folic acid and vitamin B(12) significantly reduces the incidence and severity of toxicities without compromising the antitumor activity of pemetrexed. With its innovative mode of action, proven efficacy, favorable toxicity profile and convenient administration, pemetrexed represents a new therapeutic option for the treatment of advanced NSCLC.

Antimetabolites, Antineoplastic↗
PubMed2004

Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer.

BACKGROUND: We designed a prospective study to test epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) in resected stage I-IIIA non-small-cell lung cancer (NSCLC) and to correlate overexpression with survival. PATIENTS AND METHODS: EGFR expression was evaluated in 130 consecutive NSCLC patients after radical surgery (60 squamous cell carcinomas, 48 adenocarcinomas, 22 large cell carcinomas: stage I, 41 (31%); stage II, 37 (29%) and stage IIIA, 52 (40%). RESULTS: Overall, 101 of 130 (78%) specimens expressed EGFR, and with a cut-off value of 10% positive cells 48 cases (37%) were classified as positive. At univariate analysis, EGFR was significantly more expressed in stage III (50%) than stage I (20%) and stage II (25%) (P <0.03). No correlation with histotype was found. After a median follow-up of 84 months, both median survival time (18 versus 50 months), 2-year (43% versus 70%) and 5-year (31% versus 46%) survival rates of positive cases were significantly lower than negative ones [P <0.001; hazard ratio 1.96; 95% confidence interval (CI) 1.16-3.30]. At the multivariate analysis, EGFR overexpression and stage emerged as independent factors for cancer-related mortality. CONCLUSION: In patients with radically resected stage I-IIIA NSCLC, EGFR overexpression predicts shorter survival, thus representing a valuable prognostic factor.

Adenocarcinoma↗
PubMed2002

Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer.

PURPOSE: To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin (reference regimen) in response rate for patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to receive gemcitabine 1,250 mg/m(2) days 1 and 8 plus cisplatin 75 mg/m(2) day 2 every 21 days (GC arm), or paclitaxel 225 mg/m(2) (3-hour infusion) then carboplatin (area under the concentration-time curve of 6 mg/mL x min), both on day 1 every 21 days (PCb arm), or vinorelbine 25 mg/m(2)/wk for 12 weeks then every other week plus cisplatin 100 mg/m(2) day 1 every 28 days (VC arm). RESULTS: Six hundred twelve patients were randomized to treatment (205 GC, 204 PCb, and 203 VC). Overall response rates for the GC (30%) and PCb (32%) arms were not significantly different from that of the VC arm (30%). There were no differences in overall survival, time to disease progression, or time to treatment failure. Median survival for the GC, PCb, and VC groups was 9.8, 9.9, and 9.5 months, respectively. Neutropenia was significantly higher on the VC arm (GC 17% or PCb 35% v VC 43% of cycles, P <.001), as was thrombocytopenia on the GC arm (GC 16% v VC 0.1% of cycles, P <.001). Alopecia and peripheral neurotoxicity were most common on the PCb arm, as was nausea/vomiting on the VC arm (P <.05). CONCLUSION: Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.

Adult↗
PubMed2002

Challenging the platinum combinations in the chemotherapy of NSCLC.

In previously untreated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) the combination of docetaxel and gemcitabine is active and well tolerated. In the phase II setting using a 3-week schedule, response rates (RR) ranged from 25 to 50%, and median survival from 11 to 13 months. Preliminary data with weekly and bi-weekly schedules indicate maintained efficacy while reducing the risk of neutropenia. A randomized phase III trial has shown that the combination of docetaxel and gemcitabine is as active as docetaxel plus cisplatin, achieving a 1-year survival rate of 39%, with significantly less neutropenia and gastro-intestinal toxicity. The combination of docetaxel with vinorelbine is equally active and the associated toxicities are manageable. In phase II studies the average response rate is 40%, and in one study using a 2-week schedule the 1-year survival rate was 60%. With this combination neutropenia is the commonest adverse event while clinically significant neuropathy is infrequent. In a randomized phase II trial, docetaxel plus cisplatin was compared to docetaxel plus irinotecan. The non-platinum doublet achieved comparable levels of activity, though with a different toxicity profile (more diarrhea but less nausea and vomiting). The combination of docetaxel with irinotecan and carboplatin has achieved 1-year survival of 55%. All three docetaxel combinations (gemcitabine, vinorelbine, and irinotecan) could provide a valuable alternative to platinum-based chemotherapy and should be further evaluated in phase III setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer.

Resistance to chemotherapy is common in non-small cell lung cancer. The aim of this study was to investigate the prognostic impact of in vitro established drug resistance markers on the response to chemotherapy in patients with advanced non-small cell lung cancer. Samples of 38 patients were analyzed by immunohistochemical staining, for topoisomerase IIalpha and IIbeta, Ki-67, MRP and LRP. In addition, mutation analysis of the topoisomerase IIalpha gene, the B/DNBS and the Tyr804 region, was performed. Lung tumor biopsies were taken prior for treatment with one of the following regimens; cisplatin/paclitaxel, cisplatin/VM26 or VP16, or carboplatin/VP16/ifosfamide. Seventeen patients obtained a partial response, 12 had stable disease and nine patients had progressive disease. None of the investigated markers was related with overall response rate. In one sample a point mutation in the B/DNBS region of the topo IIalpha gene was detected which substitutes IIe(510) with Val. This tumor had a partial response to four courses of cisplatin/VP16 treatment. The survival analysis showed that the patients with high topo IIalpha expressing tumors had a significantly worse survival compared with the patients with low or intermediate topo IIalpha expressing tumors. In conclusion, no relation was observed between expression of topoisomerase IIalpha, IIbeta, Ki-67, MRP or LRP and response rate. Furthermore, worse survival was seen in patients with high topoisomerase IIalpha expressing tumors. In one tumor sample, a newly described mutation in the B/DNBS region of the topo IIalpha gene was detected, which does not appear to be related to drug resistance.

ATP-Binding Cassette Transporters↗
PubMed2001

Phase II study of high-dose paclitaxel and carboplatin in previously untreated, unresectable non-small cell lung cancer.

INTRODUCTION: This phase II study was designed to assess the activity and tolerability of the carboplatin-paclitaxel combination, given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. PATIENTS AND METHODS: Sixty patients (15 stage IIIb and 45 stage IV) received paclitaxel 225 mg/ml on day 1, followed by carboplatin AUC 6 mg/ml per minute (Calvert formula) every 3 weeks. Paclitaxel was administered as a 3-h intravenous infusion followed by carboplatin over 30 min, on completion of paclitaxel administration. RESULTS: The combination showed a good safety profile with Grade 4 neutropenia occurring in 31% of patients without any serious infectious episodes requiring hospitalization. Moderate to severe anemia and thrombocytopenia seldom occurred. Sensorimotor peripheral neuropathy (Grade 2-3) and myalgia (Grade 3-4) were documented in 34 and 20% of the patients, respectively. Among 59 evaluable patients, there was one complete response and 26 partial responses for an overall response rate of 46% (95% C.I.: 34-59%). With a minimum follow-up duration of 16.5 months, the median overall survival time is 52 weeks and the 1-year survival rate is 50%. Median duration of response is 20 weeks (range: 4-52) and progression-free survival is 22 weeks (range: 5-77). CONCLUSION: In advanced NSCLC, the combination carboplatin-paclitaxel at doses of AUC 6 mg/ml per minute and 225 mg/ml every 3 weeks, is both active and relatively well-tolerated.

Adult↗
PubMed2001

Role of erythropoietin in the treatment of lung cancer associated anaemia.

Cancer-related causes of anaemia include anaemia of chronic disorders, infections, autoimmune haemolysis associated with malignant conditions, bone marrow invasion by the tumour or clonogenic marrow dysfunction, iron, folate, or vitamin B 12 deficiency and bleeding from tumour erosion. Treatment-related anaemia results from chemotherapy, radiotherapy and bone marrow fibrosis. Severe anaemia increases the burden of treatment, contributes to fatigue, reduces the quality of life and may also delay or limit further treatment. Blood transfusion is currently the most common form of treatment and patients rarely require transfusion unless the haemoglobin is less than 8 g/l. It is often difficult to predict which patients will develop anaemia and require treatment, but the proportion of patients receiving transfusions increases markedly if the pre-treatment haemoglobin concentration is below 10 g/dl. Four studies have systematically evaluated the effects of erythropoietin on anaemia in lung cancer patients and each of these trials is likely to contribute information concerning the clinical benefit of erythropoietin in treating or preventing treatment-related or disease-related anaemia. Most of the improvements in quality of life observed with erythropoietin administration occurred with haemoglobin levels between 10 and 12 g/dl, and not with levels between 7 and 10 g/dl, with a plateau effect above 12 g/dl. Consequently, a 'functional' level of haemoglobin that appears to be more important is 12 g/dl, because it may be favourably associated with a significant improvement in fatigue compared with lower haemoglobin levels. This 'functional' level would be in keeping with the body's physiological erythropoietin response.

Anemia↗