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Biomedical subjects

G Paoletti

Publications and source records attributed to G Paoletti.

At least 19 recordsLinked to original sources
PubMed2006

High activity of salvage treatment with biweekly paclitaxel-gemcitabine combination in heavily pretreated breast cancer patients.

The treatment of refractory metastatic breast cancer is primarily palliative, without a significant impact on overall survival. Among the innovative combinations in this unfavourable setting, paclitaxel and gemcitabine showed a possible synergistic action and an encouraging activity in some clinical trials. This phase II study was carried out to evaluate paclitaxel-gemcitabine combination in very heavily pretreated advanced breast cancer on a bi-weekly schedule.Thirty-nine women with advanced breast cancer were treated with paclitaxel 150 mg/m2 as 3 hrs infusion, and gemcitabine 1,500 mg/m2 as 30 mins infusion, both drugs administered on days 1, 15, with cycles repeated every 28 days. All but two patients received granulocyte colony stimulating factor (G-CSF) on days 7 to 9 and 20 to 22 of every cycle. More than two third (71%) of the patients had previously received two or more chemotherapy regimens for advanced disease, including almost all active agents in this disease. Objective responses were observed in 18 out of 34 evaluable patients (53%; 95% CI, 36% to 70%). Disease remained stable in 7 patients (21%). Responses by sites were 67% in soft tissue and in bone, and 48% in visceral disease. Median time to progression and overall survival were 9 and 20 months, respectively. Treatment was well tolerated, with G3-4 neutropenia in 8%, and G 1-2 thrombocytopenia in 13% of the patients; non-hematological toxicities were mild, with G3 hepatotoxicity in 5% of the patients, and G3 peripheral neurotoxicity in 10% of the patients. Biweekly paclitaxel/gemcitabine combination with G-CSF support appears to be very active as salvage therapy in heavily pretreated breast cancer patients, with a very favourable safety profile.

Adult↗
PubMed2005

Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study.

The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73-1.09) for patients receiving FA and 0.99 (95% CI 0.80-1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80-1.30) and 0.94 (95% CI 0.73-1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients.

Adult↗
PubMed2005

Epirubicin, cisplatin and docetaxel combination therapy for metastatic gastric cancer.

BACKGROUND: Docetaxel is a new agent with activity in metastatic gastric cancer. This phase II study was designed to evaluate the activity and safety of an epirubicin, cisplatin and docetaxel combination in patients with this disease. PATIENTS AND METHODS: Forty-six patients with gastric adenocarcinoma with measurable distant metastasis were eligible for the study. Patients received epirubicin 50 mg/m(2) and docetaxel 60 mg/m(2), on day 1, and cisplatin 60 mg/m(2) on day 2. Granulocyte colony-stimulating factor 300 mug/day subcutaneously was given on days 5 and 6. Cycles were repeated every 3 weeks for a maximum of eight courses. RESULTS: All patients were evaluable for response and toxicity. Two complete and 21 partial responses were observed, with an overall response rate of 50% [95% confidence interval (CI) 36% to 64%]. Stable disease was observed in 13 patients (28%) and progressive disease in 10 patients (22%). The median time to progression was 6 months (95% CI 5-7) and the median overall survival was 11.2 months (95% CI 8.5-13.9). Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 46%, 7% and 13% of patients, respectively. There were five episodes of febrile neutropenia in four patients. Other grade 3 toxicities included mucositis in three patients (6.5%), vomiting in four patients (8.7%) and diarrhea in one patient (2%). There were no cardiac toxicity, severe neurotoxicity or treatment-related deaths. CONCLUSIONS: The epirubicin, cisplatin and docetaxel combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric cancer and deserves further evaluation in randomized studies.

Adenocarcinoma↗
PubMed2005

FOLFIRI regimen in advanced colorectal cancer: the experience of the Gruppo Oncologico dell'Italia Meridionale (GOIM).

PURPOSE: To verify the experience of the GOIM in the treatment of advanced colorectal cancer patients with the FOLFIRI combination therapy. PATIENTS AND METHODS: Patients entered in three consecutive trials of the GOIM (protocols no. 9706, 9901, and 2301) were reported in this analysis. A total of 287 chemotherapy-naive patients were treated with FOLFIRI regimen: Irinotecan 180 mg/m(2) on day 1 with LV5FU2 regimen (LV at 100 mg/m(2) administered as a 2-hour infusion before FU at 400 mg/m(2) as an intravenous bolus injection, and FU at 600 mg/m(2) as a 22-hour infusion immediately after 5FU bolus injection on day 1 and 2); the treatment was repeated every 2 weeks. RESULTS: 287 patients entered in these three trials, and 264 (92%) were evaluable for response. The overall response rate was 34.5% (95% confidence interval [CI]: 29% to 40%). When only assessable patients were analyzed, overall response rate was 37% (95% CI: 31% to 43%). Median time to progression, median duration of response and survival were 7 months, 10.5 months and 14 months, respectively. All but three patients were evaluable for toxicity which was globally mild; grade 3-4 toxicity was uncommon, and gastrointestinal disturbances were the most common. CONCLUSIONS: FOLFIRI regimen is effective and well-tolerated as first-line treatment in patients with advanced colorectal cancer. Further studies needed to evaluate the improvement in results with the addition of new drugs to this combination therapy.

Adult↗
PubMed2000

5-Fluorouracil and folinic acid with or without CPT-11 in advanced colorectal cancer patients: a multicenter randomised phase II study of the Southern Italy Oncology Group.

PURPOSE: The combination regimen CPT-11 plus bolus and infusion 5-fluorouracil (5-FU) with high-dose leucovorin (hybrid regimen LV5FU2) has been tested for activity and toxicity against advanced colorectal carcinoma in a randomised, multicenter phase II trial. PATIENTS AND METHODS: A total of 102 chemotherapy-naïve patients were randomised in a 1:2 fashion to receive: leucovorin 100 mg/m2 administered as a two-hour infusion before 5-FU 400 mg/m2 as an intravenous bolus, and FU 600 mg/m2 as a 22-hour infusion immediately after 5-FU bolus injection repeated on days 1 and 2 (LV5FU2 regimen, arm A, 34 patients) or CPT-11 at 180 mg/m2 (150 mg/m2 for patients of age > or = 70 and < 75 years) only on day 1 immediately before LV5FU2 therapy (LV5FU2 + CPT-11 regimen, arm B 68 patients). Both treatments were repeated every two weeks. The presence of a calibration arm assured consistency and more realistic evaluation of results achieved with the LV5FU2 + CTP-II regimen. RESULTS: Thirty-three and sixty-four patients were evaluable in arm A and B, respectively. The overall response rate was 18% in arm A (95% CI: 7%-34%) and 40% in arm B (95% CI: 28%-52%). Median time to progression, median duration of response and survival were similar in both groups. Responders (CR + PR) survived statistically longer than non-responders only in arm B (20 vs. 10 months, P = 0.0016). All patients were evaluable for toxicity which was mild in both groups; gastrointestinal disturbances were the most common. There were no treatment-related deaths. Grade 3-4 toxicity was uncommon in both arms. CONCLUSIONS: The addition of CPT-11 to the hybrid LV5FU2 regimen provided a significant overall response rate (40%) with relatively mild toxicity. The overall response rate was 18% in patients treated with LV5FU2 alone in the calibration arm. Thus, considering other encouraging data from the literature, the CPT-11 + FU-LV combination therapy can be regarded as a new, very effective treatment option for first-line treatment of advanced colorectal cancer patients.

Adult↗
PubMed1998

Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas.

PURPOSE: We conducted a randomized trial to evaluate primarily the cardioprotective effect of dexrazoxane (DEX) in patients with advanced breast cancer and soft tissue sarcomas (STS) treated with high-dose epirubicin (EPI). We wished also to determine the value of radioimmunoscintigraphy (RIS) in the assessment of anthracycline cardiotoxicity. PATIENTS AND METHODS: Patients with breast cancer (n = 95) or STS (n = 34) received EPI 160 mg/m2 by intravenous (I.V.) bolus every 3 weeks with or without DEX 1,000 mg/m2 I.V. Cardiac monitoring included multigated radionuclide (MUGA) scans with determination of resting left ventricular ejection fraction (LVEF), and RIS with indium 111 antimyosin monoclonal antibodies. RESULTS: In either disease, antitumor response rates, time to progression, and survival did not significantly differ between the two arms. There was little difference in noncardiac toxicity for the two treatment groups. All methods of cardiac evaluation clearly documented the cardioprotective effect of DEX. Four patients developed congestive heart failure (CHF), all in the EPI arm. The decrease in LVEF from baseline was significantly greater in the control group. An abnormal antimyosin uptake was observed early in both arms and progressively increased during treatment. However, this increase was significantly higher in the EPI group (P = .004). CONCLUSION: DEX significantly protects against the development of cardiotoxicity when high single doses of EPI are used. Apparently, there was no evidence of an adverse impact of DEX on antitumor activity. Although RIS is a sensitive technique in detecting anthracycline cardiac damage, its specificity is low and it cannot be considered a primary test for guiding anthracycline treatment.

Adult↗
PubMed1996

Insulin exerts opposite effects on platelet function at physiological and supraphysiological concentrations.

In this study, we investigated the effects of a 3-min insulin incubation both at physiological and at supraphysiological concentrations on platelet aggregation and intraplatelet cyclic guanosine monophosphate (cGMP) levels both in the absence and in the presence of phosphodiesterase inhibition. We observed that insulin at concentration in the range 0.25-2 nmol/L decreases platelet response to adenosine 5-diphosphate (ADP), being Effective Dose 50 (ED50) for ADP with 2 nmol/L insulin 164 +/- 15% of the basal value, p = 0.005; furthermore, insulin increases intraplatelet content of cGMP (from basal 7.3 +/-0.6 pmol/10(9) plts to 14.6 +/- 1.2 pmol/10(9) plts with 2 nmol/L insulin, p=0.0001) and does not affect the platelet cGMP increase induced by nitrates. On the contrary, at very elevated concentrations (25-200 nmol/L) insulin increases platelet aggregation to ADP (ADP ED50 with 200 nmol/L insulin being 81 +/- 4% of the basal value, p = 0.01), decreases intraplatelet content of cGMP (from basal 7.2 +/- 0.1 pmol/10(9) plts to 5.7 +/- 0.2 pmol/10(9) plts with 200 nmol/L insulin, p = 0.01) and attenuates the platelet cGMP increase induced by nitrates. When cGMP catabolism is inhibited by theophylline or the selective cGMP phosphodiesterase inhibitor zaprinast, insulin shows anti-aggregating effects also at highly supraphysiological concentration (25-200 nmol/L). These results indicate that insulin, depending on the concentrations employed, shows opposite effects on platelet function, and they provide information about the mechanisms involved: actually, insulin is able to increase both cGMP synthesis, through guanylate cyclase activation, and cGMP catabolism, through phosphodiesterase activation. At physiological or slightly supraphysiological concentrations the first phenomenon is prevailing, so that cGMP intraplatelet values increase and insulin shows antiaggregating properties, whereas, at supraphysiological concentrations, insulin reduces cGMP levels through a prevailing phosphodiesterase activation, as supported by the fact that, when cGMP catabolism is prevented, insulin shows anti-aggregating properties also at the highest concentrations used.

Adenosine Diphosphate↗
PubMed1995

Intrapatient comparison of single-agent epirubicin with or without lonidamine in metastatic breast cancer.

The aim of this study was to determine if lonidamine (LND) supplementation to single-agent epirubicin (EPI) could reverse anthracycline resistance in patients with metastatic breast cancer. 45 patients with metastatic breast cancer were treated with EPI 120 mg/m2 by intravenous (i.v.) bolus every 3 weeks. Patients who progressed were given the same chemotherapy regimen on day 4 in combination with oral LND, 150 mg on day 1, 300 mg on day 2 and 450 mg on days 3-5. Among the 40 evaluable patients, 6 complete responses (CR) and 14 partial responses (PR) were achieved with EPI treatment alone for an overall response rate of 50%. The median duration of response was 6.5 months. Among the 25 patients treated with EPI+LND, 5 PR (21% of 24 evaluable patients) were observed with a median duration of response of 7 months. The median survival in patients receiving both treatments was 20 months. The survival for all patients was 18 months. The survival of patients receiving LND was not significantly longer than for the other patients. Myelotoxicity was the most common side-effect followed by alopecia, nausea and vomiting, and stomatitis. LND-related toxic effects were mild-to-moderate epigastralgia and myalgia. Anthracycline-related toxicity was the same in the two treatment groups. This study indicates that LND may circumvent clinical resistance to EPI without altering the pattern or severity of the toxicity of this anthracycline. Continued investigation of the clinical modulation of EPI resistance by LND in breast cancer is warranted, hopefully in patients with known multidrug resistance status.

Adult↗
PubMed1995

Sequential biochemotherapy for metastatic colorectal cancer using fluorouracil, folinic acid, thymopentin and interleukin-2: clinical and immunological effects.

BACKGROUND: A phase II study was performed to evaluate the clinical and immunological effects of a regimen of fluorouracil (5-FU) and folinic acid (FA) combined with thymopentin (TP-5) and interleukin-2 (IL-2) in the treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Forty-five evaluable patients with measurable colorectal cancer and no prior therapy for metastatic disease were treated with 5-FU 400 mg/m2/d and FA 200 mg/m2/d i.v. on days 1-5, TP-5 50 mg s.c. on days 8-11, and IL-2 9 MU/m2 s.c. twice daily on days 12-16. Cycles were repeated at 4-week intervals if toxicity had resolved. Immunological changes were evaluated in 13 patients and compared with a well matched series of 13 patients treated with the same regimen without TP-5. RESULTS: Two complete responses and 17 partial responses were seen (42%; 95% confidence interval, 28% to 56%). Fifteen patients (33%) had stable disease. The median time to progression was 8.5 months and the median survival 13 months. Treatment was reasonably well tolerated, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Hematological and immunological changes during treatment were qualitatively similar to those expected with IL-2 +/- chemotherapy. Quantitatively, significant changes (higher levels of IL-2, CD25 and IFN-gamma, and lower levels of sIL-2R) were observed in patients given TP-5. CONCLUSION: The combination of 5-FU + FA and TP-5 + IL-2 is effective in advanced colorectal cancer with acceptable toxicity. Immunological data suggest that TP-5 may modulate the action of IL-2 in the clinical setting. However, improved treatment approaches are needed, and the interactions between thymic hormones and cytokines should be further explored.

Adult↗
PubMed1993

Phase II study of continuous intravenous infusion of recombinant interleukin-2 in patients with advanced renal cell carcinoma.

BACKGROUND: The goal of this study was to evaluate the therapeutic efficacy and toxicity of recombinant interleukin-2 (rIL-2) administered by continuous intravenous (CIV) infusion to patients with metastatic renal cell cancer (RCC). PATIENTS AND METHODS: Thirty patients with RCC were given rIL-2 18 MIU/m2/d CIV. The schedule consisted of two induction cycles and four maintenance cycles with a 3-week rest period between cycles. Each induction cycle consisted of two infusion periods lasting 120 and 108 hours, respectively, separated by a 6-day rest period. Each maintenance cycle consisted of a 120-hour infusion period. RESULTS: Among 29 assessable patients, the objective response rate was 14% (95% confidence interval, 2% to 26%); one patient achieved a complete response, and 3 partial responses. Ten patients (34%) had stable disease (SD). Median survival was 11 months. Toxicity was generally manageable. Hypotension was universal, but required dose reduction in only 2 patients. Increase in serum creatinine levels was observed in 20 patients, and returned to normal in all but 4 patients after discontinuation of treatment. CONCLUSION: Results confirm the efficacy of rIL-2 in patients with RCC and the feasibility of the treatment in a normal oncology ward. However, responses are observed in a minority of patients, and treatment-related toxicity, as well as technical problems, may be troublesome to many patients.

Adult↗
PubMed1991

Thymopentin and interleukin-2 in combination with 5-fluorouracil and leucovorin in metastatic colorectal adenocarcinoma: preliminary results.

Thymic hormones have been shown to exhibit immunorestorative effects in vivo and in vitro, and to enhance the expression of high affinity interleukin-2 (IL-2) receptors on normal human lymphocytes stimulated with phytohemagglutinin. Based on these data, a clinical trial was initiated to determine the effects of the combination of 5-fluorouracil (5-FU) and folinic acid (FA) with thymopentin (TP-5) and interleukin-2 (IL-2) in patients with advanced colorectal carcinoma. Fifteen patients were treated with FA, 200 mg/m2/day by IV bolus, and 5-FU, 400 mg/m2/day as a 30-minute infusion, both given for 5 consecutive days every 28 days. TP-5, 50 mg/day, was administered subcutaneously on days 8-11, and IL-2, 9 million IU/m2 twice daily, was given subcutaneously on days 12-16. Of 8 patients evaluable for response, 4 achieved a response. Two patients had stable disease, and two progressed during treatment. There were no instances of life-threatening toxicity. Two patients developed grade III stomatitis and diarrhea followed by leukopenia and fever, requiring hospitalization. Other toxicities were moderate. These results are only preliminary, and a larger number of patients and longer follow-up are needed to draw meaningful conclusions about the merits of this new approach in cancer treatment.

Adenocarcinoma↗
PubMed1991

[Acute myocardial infarction promptly complicated by atrial fibrillation during Holter recording].

We observed, during Holter recording, a case of inferior acute myocardial infarction complicated by paroxystic hyperkinetic atrial fibrillation, which occurred 12 min after the onset of acute irreversible myocardial ischemia. The atrial fibrillation was preceded by a complex pattern of hyperkinetic supraventricular arrhythmias characterized by single premature supraventricular beats, paired premature supraventricular beats and many runs of paroxystic supraventricular tachycardia. The most plausible hypothesis is that atrial fibrillation and the preceding arrhythmic pattern have been due to an extension of ischemia from ventricular to atrial myocardium.

Atrial Fibrillation↗
PubMed1991

A comparison of metoprolol OROS with antenolol in the treatment of effort angina pectoris: a randomized double-blind study.

The antianginal efficacy of metoprolol OROS has been investigated in comparison with that of atenolol in a multicenter double-blind cross-over trial carried out in patients with stable effort angina. OROS (ORally OSmotic) is a new semi-permeable delivery system with very slow osmotic release of the active drug, which is maintained at virtually constant plasma levels throughout the 24 hours. At the end of a 2-week run-in period, 53 patients with chronic coronary artery disease and documented ischemia during bicycleergometric exercise test were given, on double-blind condition, metoprolol OROS 21/285 and atenolol 100 mg in random order for 4 weeks each. On the last day of each cross-over period, patients underwent a bicycleergometric exercise test 24 hours after the last drug intake. The mean number of anginal attacks (2.54 during the 2-week run-in period) decreased under both metoprolol OROS (1.29 and 1.13 after 2 and 4 weeks of treatment, respectively) and atenolol (1.29 and 0.73 after 2 and 4 weeks of treatment, respectively), with no difference between the two beta-blockers. The same behaviour was observed as regards the nitroglycerin tablets consumption. The exercise test variables (i.e. duration of exercise, maximum workload and peak exercise values of systolic and diastolic blood pressure, heart rate and ST-segment depression) did not differ between the two treatments and did not show a time-effect. The percentage of patients reporting adverse effects was low with both treatments. Two patients were withdrawn from the study during atenolol (gastralgia and heartburn, respectively), and one during metoprolol OROS (gastralgia).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Fluorouracil, doxorubicin, and cyclophosphamide versus fluorouracil, doxorubicin, and cyclophosphamide plus lonidamine for the treatment of advanced breast cancer: a multicentric randomized clinical study.

Experimental models have demonstrated the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-potentiating activity of lonidamine. Phase II clinical trials on advanced breast cancer have shown that this drug induced a 16% objective response rate. Present multicentric randomized trial was conducted to verify whether lonidamine can potentiate the antineoplastic effects of conventional fluorouacil, Adriamycin, cyclophosphamide (FAC) chemotherapy in advanced breast cancer. From January 1987 to December 1989, 265 patients were enrolled in this study, and 231 are evaluable for response. After stratification according to institution and ECOG performance status (PS), the patients were randomly allocated to receive either standard FAC therapy (group A) or FAC plus lonidamine (600 mg orally daily three times a day) (group B). After three FAC courses, the patients with no progressive disease were further randomized to either receive continuous treatment up to the time of tumor progression (maximum: 10 courses) or to discontinue therapy when a response "plateau" was reached. In this latter group, the same therapy was restarted at relapse or disease progression. Objective response (complete response plus partial response) was significantly higher in group B (66.3%) compared to group A (42.3%). The actuarial median times to disease progression was also significantly longer (P less than 0.0001) in group B (median 9 months) than in group A (median 6 months). Other than myalgia and gastric pain, no increased toxicity was observed in the lonidamine. The analysis of second randomization are yet available because of the longer follow-up time required. Present findings suggest an interesting additive effect of lonidamine when combined with FAC chemotherapy and warrant further investigation in other therapeutic regimens and in other neoplastic diseases.

Adult↗
PubMed1988

Chemoprophylaxis of bacterial infections in granulocytopenic cancer patients using norfloxacin.

Sixty-five cancer patients pretreated with chemo or radiotherapy, with granulocytopenia less than 1000/mm3 and without fever, were entered into this study: 30 of them were submitted to prophylaxis with norfloxacin while the remaining 35 patients were used as a control group. 20% of the treated subjects versus 68.6% of the controls presented a subsequent infection (P less than 0.001), the lung representing the most frequent site of the infectious disease in both groups (3/6 and 14/24 respectively). These data strongly suggest the use of norfloxacin as an effective prophylactic drug in nonfebrile, granulocytopenic cancer patients, especially as far as gram-negative infections are concerned. Because of the high prevalence of lung cancer in the patients of our study, and a related prevalence of lung infections, at the present time, a wider use of this antibiotic in every kind of solid tumor cannot be generalized.

Agranulocytosis↗