15617 Background: SM is a tyrosine kinase inhibitor recently approved for treatment of mRCC. Side effects of treatment have been investigated in 51 pts with mRCC and 35 out 51 enrolled pts resulted evaluable for response. Methods: Pts were clinically evaluated before therapy and each month during SM treatment; haematological and biochemical parameters were measured after each cycle. Thyroid function was also evaluated measuring thyroid-stimulating-hormone (TSH), serum free thyroxine (FT4) and triiodothyronine (FT3), before the start and after 6 months of treatment. Results: Toxicity was evaluated according to NCI-CTC. Neutropenia grade 3 was observed in 7 pts (13,7%), grade 2 in 13 (25%); anemia grade 3 was found in 3 pts (5,8%) and grade 2 in 6 (11,7%); thrombocytopenia grade 3 was found in 6 pts (11,7%), grade 2 in 5 (9,8%). Mucositis resulted a frequent side effect. In fact, 4 (7,8%) pts showed a grade 3 toxicity, 16 (31,3%) grade 2 and 10 (19,8%) grade 1 Among 29 out 35 (82,8%) pts who responded to therapy, 3 had mucositis grade 3, 15 grade 2, 9 grade 1. Conversely, among 6 out 35 (17,1%) pts who had progressive disease during treatment, mucositis was observed in only 2 pts. 24 pts out 35 who received 6 months SM treatment were reevalueted for thyroid function. No patient had thyroid dysfunction before treatment. Conversely, 8 pts showed severe ipothyroidism (TSH, FT3 and FT4 out of the normal range) and 6 others intermediate ipothyroidism (only TSH increased over 20 μU/ml) after at least 6 cycles of therapy. Conclusions: SM therapy represents a new interesting approach to the treatment of mRCC, but shows noteworthy side effects. Regular monitoring of thyroid function with administration of levothyroxin substitutive treatment at the appearance of the thyroid disfunction is required. A direct correlation between grade 2–3 mucositis and clinical response to treatment could be postulated on the basis of our data, although a statistical analysis on a greater cohort of subjects is required to confirm this observation. No significant financial relationships to disclose.

The aim of this study was to assess whether a combination of gemcitabine (GEM) with either paclitaxel (PTX) or vinorelbine (VNR) could be more effective than GEM or PTX alone in elderly or unfit advanced non-small-cell lung cancer (NSCLC) patients. A total of 264 NSCLC patients aged >70 years with ECOG performance status (PS)⩽2, or younger with PS=2, were randomly treated with: GEM 1200 mg m −2 on days 1, 8 and 15 every 28 days; PTX 100 mg m −2 on days 1, 8 and 15 every 28 days; GEM 1000 mg m −2 plus PTX 80 mg m −2 (GT) on days 1 and 8 every 21 days; GEM 1000 mg m −2 plus VNR 25 mg m −2 (GV) on days 1 and 8 every 21 days. In all arms, an intra-patients dose escalation was applied over the first three courses, provided that no toxicity of WHO grade ⩾2 had previously occurred. At present time, 217 (82%) patients had died. The median (months) and 1-year survival probability were 5.1 and 29% for GEM, 6.4 and 25% for PTX, 9.2 and 44% for GT, and 9.7 and 32% for GV. Multivariate analysis showed that PS⩽1 (hazard ratio (HR)=0.67; 95% CI 0.51–0.90), and doublet treatments (HR=0.76; 95% CI 0.59–0.99) were significantly associated with longer survival. Doublets produced no more toxicity than single agents. GT should be considered a reference regimen for elderly NSCLC patients with PS⩽1.

Gemcitabine plus vinorelbine (GV) or paclitaxel (GT) vs gemcitabine (G) or paclitaxel (T) alone in elderly or unfit non-small cell lung cancer (NSCLC) patients. SICOG 9909 phase III trial / Bianco, Andrea; Frasci, G; Comella, P; De Cataldis, G; Del Gaizo, F; Lorusso, V; Panza, N; Mazzarella, G; Muci, D; Buzzi, F; Gambardella, A; Marsico, A. Comella G.. - In: EUROPEAN RESPIRATORY JOURNAL. - ISSN 0903-1936. - 22, ::Suppl 45(2003), p. 527s (3312) … Non ci sono file associati a questo prodotto … I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione … Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2018-2020 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori …

Immune function in acromegalic patients has been poorly investigated. The aim of this study was to evaluate the main surface antigen clusters of circulating lymphocytes in acromegaly. One hundred patients with active acromegaly (55 women and 45 men, aged 20–70 yr) and 200 healthy subjects sex- and age-matched with the patients (110 women and 90 men, aged 20–70 yr) were enrolled in this study. All patients and controls were born and live in Southern Italy. No patient had received octreotide, bromocriptine or corticosteroids for at least 3 months before entering the study. The analysis of lymphocyte subset pattern was performed by flow cytometry and fluorescein isothiocyanate or phycoerythrin directly conjugated monoclonal antibodies specific for the cell surface antigen clusters (CD) representing T-cell population as a whole (CD3), T helpers (CD4), T suppressors (CD8), natural killer cells (CD16) and B-cell population as a whole (CD19). Acromegalics had significantly increased levels of CD3 (67.1±7.2 vs 64.3±8.8%; p =0.03) and CD4 (37.8±3.5 vs 36.4±4.3%; p =0.004) and decreased levels of CD8 (31.4±3.3 vs 33.7±8.2%; p lt0.01) and CD19 (12.1±3.1 vs 15.2±5.1; p =0.01) without age-difference. The results of the current study demonstrate an increase in T-cell activity together with a decrease in B-cell activity in a very large series of patients with active acromegaly. These data further support the existence of abnormalities of the immune system in patients with chronic GH/IGF-I excess.

BACKGROUND:The aim of our study was to determine the maximum tolerated dose of paclitaxel combined with a fixed dose of gemcitabine and vinorelbine in the treatment of non-small-cell lung cancer (NSCLC) and to evaluate in a phase II trial the efficacy of this combination.PATIENTS AND METHODS:Sixty-two patients with stage IIIB/IV NSCLC were treated with paclitaxel in escalating doses from 40-80 mg/m(2) combined with gemcitabine and vinorelbine at fixed doses of 1000 mg/m(2) and 25 mg/m(2), respectively. All drugs were given intravenously on day 1 and 8 every 3 weeks.RESULTS:In a phase I trial, carried out on 21 patients, grade 4 neutropenia, as dose-limiting toxicity, occurred at the dosage level of paclitaxel 80 mg/m(2). In a phase II trial, with paclitaxel administered at 70 mg/m(2), 27 out of 41 (66%) assessable patients responded (10% complete responses and 56% partial responses). Objective response was observed in 13 of 16 patients (81%) with stage IIIB disease and in 14 of 25 (56%) with stage IV disease. The median time to treatment failure was 26 weeks (range 3-72 weeks; 32 weeks and 20 weeks for stages IIIB and IV, respectively) and median survival 62 weeks (range 4-176 weeks; 72 weeks and 56 weeks for stages IIIB and IV, respectively). One-year survival was 64% for all patients (72% for patients with stage IIIB and 52% for those with stage IV). Grade 3 and 4 neutropenia were observed in 11 (27%) and seven (17%) cases, respectively; grade 3 thrombocytopenia was observed in three patients (7%) and grade 3 anemia in four patients (10%). The most relevant non-hematological toxicity was grade 2/3 asthenia, which was observed in 12 patients (29%). Alopecia was almost universal, whereas nausea and vomiting were absent.CONCLUSIONS:The combination of paclitaxel, gemcitabine and vinorelbine is effective and tolerable in the treatment of NSCLC. The high activity and low toxicity of this regimen warrant randomized studies with platinum-containing combinations.

The present study was aimed at defining the antitumour activity of the cisplatin-paclitaxel-topotecan (CPT) weekly administration with G-CSF support in chemo-naive SCLC patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients received cisplatin 40 mg/m2, paclitaxel 85 mg/m2, and topotecan 2.25 mg/m2weekly, with G-CSF (5 μg/kg days 3–5) support, for a maximum of 12 weeks. 37 patients were treated, for a total of 348 cycles delivered. 8 complete responses (22%) and 22 partial responses (59%) were recorded, giving an 81% [95% CI = 65–92%] ORR. At a 13-month (range, 4–26) median follow-up, median progression-free and overall survival were 8 months and 12.5 months, with 1-year and 2-year projected survivals of 55% and 21%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 3 patients, respectively. Only one case of neutropenic sepsis was recorded, while haemorrhagic thrombocytopenia was never observed. Diarrhoea, paraesthesias and fatigue were the main nonhaematologic toxicities being severe in 6, 2 and 10 patients, respectively. The weekly CPT combination with G-CSF support represents a well tolerated therapeutic approach in chemo-naive ED-SCLC patients. The activity rate seems at least similar to that achievable with the standard front-line approaches. © 2001 Cancer Research Campaign http://www.bjcancer.com

Bajardi, E., see Valerio, MR 34 (4), S31 Bania, H., see Agelaki, S. 34 (4), S77 Belli, M., see Frasci, G. 34 (4), S65 Bianco, A., see Frasci, G. 34 (4), S65 Blazoyiannakis, G., see Agelaki, S. 34 (4), S77 Boccieri, MG, see Tumolo, S. 34 (4), S37 Bruschi, G., see Tumolo, S. 34 (4), S37

IRIS è la soluzione IT che facilita la raccolta e la gestione dei dati relativi alle attività e ai prodotti della ricerca. Fornisce a ricercatori, amministratori e valutatori gli strumenti per monitorare i risultati della ricerca, aumentarne la visibilità e allocare in modo efficace le risorse disponibili … " Gemcitabine + Vinorelbine (GV) Vs Gemcitabine + Paclitaxel (GT) Vs Gemcitabine (G) Vs Paclitaxel (P) in elderly NSCLC patients" … " Gemcitabine + Vinorelbine (GV) Vs Gemcitabine + Paclitaxel (GT) Vs Gemcitabine (G) Vs Paclitaxel (P) in elderly NSCLC patients" / Frasci, G; Comella, P; Lo Russo, V; Panza, N; Nicolella, G; Bianco, Andrea; G., De Cataldis; M., Belli; A., Iannelli; B., Massidda; S., Mancarella; P., Masullo; G., Comella; De Lena, M; on behalf of Southern Italy Cooperative Oncology, Group. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 11, Suppl 2(2000), p. 6 (A22) … " Gemcitabine + Vinorelbine (GV) Vs Gemcitabine + Paclitaxel …

PURPOSE To evaluate whether the addition of gemcitabine (G) to vinorelbine (V) improves survival and quality of life (QoL) among elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with NSCLC aged >/= 70 years with advanced disease were randomly allocated to receive V 30 mg/m(2) on days 1 and 8 every 3 weeks or G 1,200 mg/m(2) + V 30 mg/m(2) on days 1 and 8 every 3 weeks. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned based on the first 60 patients per arm. RESULTS In May 1999, the survival data were analyzed of 120 eligible patients (V group = 60; G + V group = 60) who had been randomized from June 1997 to February 1999. Forty-nine patients had stage IIIB disease, and 71 had stage IV. At a median potential follow-up of 14 months (range, 3 to 22 months), 93 patients had died (G + V group = 41; V group = 52). In the G + V group, median survival time was 29 weeks and projected 1-year survival was 30%; these values were 18 weeks and 13% in the V group. According to multivariate Cox analysis, the risk of death in the G + V arm compared with the V arm was 0.48 (95% confidence interval, 0. 29 to 0.79; P <.01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The overall response rates were 22% and 15% in the G + V and V groups, respectively. CONCLUSION In elderly patients with NSCLC, G + V treatment is associated with significantly better survival than is V alone.

PURPOSE:In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non-small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG). PATIENTS AND METHODS:From April 1997, patients with locally advanced or metastatic NSCLC, an age of < or = 70 years, and an Eastern Cooperative Oncology Group performance status < or = 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m(2), gemcitabine 1,000 mg/m(2), and vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m(2) on days 1 and 29 and vinorelbine 30 mg/m(2)/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival. RESULTS:The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P <.01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen. CONCLUSION:The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.

PURPOSE: To determine the maximum-tolerated dose of gemcitabine when combined with a fixed dose of vinorelbine in the treatment of non–small-cell lung cancer (NSCLC) and to evaluate in a phase II trial the activity of this combination. PATIENTS AND METHODS: Sixty-eight patients with stage IIIB/IV NSCLC were treated with vinorelbine at fixed dose of 30 mg/m2 intravenously and gemcitabine at increasing dose levels from 800 to 1,500 mg/m2 intravenously on days 1 and 8 every 3 weeks. RESULTS: In phase I, dose-limiting toxicity occurred at the dosage of 1,500 mg/m2 gemcitabine, with three of five patients developing grade 4 thrombocytopenia. In phase II, with gemcitabine at 1,200 mg/m2, 19 (36%) of 52 assessable patients responded. Objective response was observed in 11 (39%) of 28 patients with stage IIIB disease and in eight (33%) of 24 patients with stage IV. The median time to progression was 29 weeks (range, 2 to 41 weeks; 35 weeks and 16 weeks for stages IIIB and IV, respectively), and median survival was 54 weeks (range, 2 to 84+ weeks; 63 weeks and 42 weeks for stages IIIB and IV, respectively). One-year survival was 64% for patients with stage IIIB disease and 29% for those with stage IV. Clinical benefit response was observed in 29 (59%) of 49 assessable patients. Grade 4 leukopenia and thrombocytopenia were uncommon (6% and 8% of cases, respectively); however, grade 3/4 leukothrombocytopenia occurred more frequently in patients aged more than 70 years (52% and 24%, respectively). CONCLUSION: The combination of vinorelbine and gemcitabine is effective and tolerable in the treatment of NSCLC, thus deserving randomized trials with cisplatin combination regimens.

BACKGROUND:To investigate the safety and effectiveness of the combination of paclitaxel, cisplatin and gemcitabine as second-line in patients with advanced non-small cell lung cancer (NSCLC) sensitive to first-line cisplatin-based chemotherapy.PATIENTS AND METHODS:From June 1997 to December 1998, 26 patients with stage IIIB or IV NSCLC received paclitaxel 125 mg/m2, as a one-hour infusion, followed by cisplatin 50 mg/m2 and gemcitabine 1000 mg/m2, intravenously, on day 1 and 8, every 3 weeks. Twenty-three patients were male; the median age was 59 years (range 44-70); The Eastern Cooperative Oncology Group performance status was 0 to 1 in 88% of patients; 16 patients had stage IV disease and 7 patients had 3 or more sites of disease. The predominant histology was adenocarcinoma in 14 patients. Prior treatment involved cisplatin plus vinorelbine in 14 patients and cisplatin plus mitomycin C plus vindesine in 12 cases.RESULTS:Seven (27%; exact 95% confidence limits: 11.6-47.8%) patients achieved a partial response to treatment whilst 7 (27%) had stable disease. The median duration of response was 22 weeks (range, 18 to 34 weeks). The median overall survival was 24 weeks (range, 8 to 36 weeks). The main toxicities were: grade 3-4 neutropenia in 9 (34%) patients; grade 2-3 peripheral neuropathy in 10 (38%); and grade 2-3 asthenia in 15 (57%) cases.CONCLUSION:The paclitaxel, cisplatin and gemcitabine combination is active as a second-line regimen in patients with advanced NSCLC, but with mild toxicity. It seems suitable for patients with advanced NSCLC as a first-line treatment.