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Biomedical subjects

D Giannarelli

Publications and source records attributed to D Giannarelli.

At least 19 recordsLinked to original sources
PubMed2006

Second- and third-generation aromatase inhibitors as first-line endocrine therapy in postmenopausal metastatic breast cancer patients: a pooled analysis of the randomised trials.

The purpose of this study was to estimate in all randomised trials the relative risk of overall response rate (ORR), clinical benefit (CB), time to progression (TTP), overall survival (OS), and toxicity of aromatase inhibitors (AI), compared with tamoxifen (Tam) as first-line endocrine therapy in postmenopausal metastatic breast cancer (PMBC) women. Prospective randomised studies were searched through computerised queries of MEDLINE, EMBASE, and the American Society of Clinical Oncology (ASCO) abstract database. Relative risk, 95% confidence interval, and heterogeneity were derived according to the inverse variance and Mantel-Haenszel method and Q statistics. Six phase III prospective randomised trials including 2787 women were gathered. A significant advantage in ORR (P = 0.042), TTP (P = 0.007), and CB (P = 0.001) in favour of AI over Tam was detected at the fixed effects model. These results were not significant at the random effects model, owing to the significant heterogeneity. On the contrary, no difference was registered for OS (P = 0.743) with no significant heterogeneity. Regarding toxicity, Tam caused more frequently thromboembolic events (P = 0.005) and vaginal bleeding (P = 0.001) compared with AI. Aromatase inhibitors appear to be superior to Tam as first-line endocrine option in PMBC women. Owing to a component of variability between the six studies analysed, the random effects estimates differed from corresponding fixed ones. Investigators should assess heterogeneity of trial results before deriving summary estimates of treatment effect.

Aromatase Inhibitors↗
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↗
PubMed2006

Early post-operative MRI: correlation with progression-free survival and overall survival time in malignant gliomas.

Forty-seven patients with Glioblastoma (42) and Anaplastic Astrocytoma (5) were studied with MR 24 hrs after surgery. In order to evaluate the role of early MR in defining the extent of surgical resection and its relation with the prognosis of malignant glioma patients, three categories of surgical resection were considered: gross total, sub-total and partial resection. The results were correlated with progression-free survival (PFS) and overall survival (ST). As demonstrated by early-MR, gross total resection was performed in 17 patients, sub-total and partial resection in 19 and 11 patients, respectively. The PFS was 6 months in gross total resection, 6 and 3 months in sub-total and in partial resection, respectively. The median survival time was 16 months in total resection patients, 13 months and 7 months in sub-total resection and partial resection patients, respectively. The study confirms that early-MR has to be considered an accurate technique for monitoring the extension of malignant glioma surgical resection and shows a good correlation between early-MR findings, PFS and ST.

Adult↗
PubMed2006

Prevalence of intestinal metaplasia in the distal esophagus in patients endoscopically suspected for short Barrett's esophagus.

The clinical importance of Barrett's esophagus is related to its correlation to adenocarcinoma. The diagnosis is based on histologic demonstration of specialized intestinal metaplasia in the distal esophagus. The aim of this study was to assess the prevalence of intestinal metaplasia of the distal esophagus in a population submitted to gastroscopy not selected for reflux disease, and with columnar lined distal esophagus between 0.5 and 2 cm. Four biopsies in the distal esophagus were done in 224 patients undergoing routine gastroscopy. Patients were not selected for gastroesophageal reflux. Other clinical parameters were recorded to assess any possible association. In four Centers 224 patients received endoscopy with biopsies demonstrating specialized intestinal metaplasia in 21% of cases. No association was present among the patients with esophagitis or hiatal hernia, as well as with reflux symptoms. A significant association was present in over 70 (females), as well as with the presence of antral intestinal metaplasia demonstrated in 45 patients by gastric biopsies. No other significant associations were present. Biopsy samplings can diagnose the presence of intestinal metaplasia during endoscopy in patients endoscopically suspected for Barrett's esophagus: at present there is not clear evidence to promote this screening to achieve mortality reduction of esophageal adenocarcinoma.

Aged↗
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

Gemcitabine and cisplatin in the treatment of elderly patients with advanced non-small cell lung cancer: impact of comorbidities on safety and efficacy outcome.

The aim of the study was to describe in detail the impact of aging and comorbidities on safety and efficacy of gemcitabine-cisplatin in the subset of elderly with advanced NSCLC. We report the results of our study which enrolled patients aged over 65 years or older. This study included 46 patients consecutively admitted to our Department. Treatment consisted of gemcitabine 1250 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 2, of a 21-day cycle. The Charlson score method was chosen to evaluate the conditions of comorbidity. All patients were evaluable for toxicity and 44 for activity. A total of 128 courses were administered, with a median of 3 courses per patient and a dose-intensity of 93% and 88% for gemcitabine and cisplatin, respectively. Grade 3-4 neutropenia (22% of patients) and grade 3 asthenia (4.5%), emesis (4.5%) and nephrotoxicity (4.5%) were the most severe adverse events. Univariate analysis of toxicity did not show any significant difference among all groups. The overall response rate was 45.6% (95% CI, 31.3-60). At a median follow up of 13 months, the median and progression-free survival were 15 and 8 months, respectively. The multivariate analysis resulted in objective response and disease control being predictive of longer survival. The combination of gemcitabine and cisplatin appears to be an effective and tolerated regimen for elderly patients with advanced NSCLC, regardless of aging and condition of comorbidities. Prospective randomized trials based on specific geriatric assessment are required to obtain compelling information for the optimal management of elderly patients with advanced NSCLC.

Age Factors↗
PubMed2005

Activity and toxicity of oxaliplatin and bolus fluorouracil plus leucovorin in pretreated colorectal cancer patients: a phase II study.

The aim of the current study was to evaluate the activity and toxicity of a combination of oxaliplatin with bolus fluorouracil and leucovorin in colorectal cancer (CRC) patients pretreated for advanced disease with various schedules including continuous fluorouracil infusion. Thirty consecutive patients with pretreated advanced CRC received oxaliplatin 130 mg/m2 by 2-h infusion dl, leucovorin 100 mg/m2 by 1-h infusion followed by fluorouracil 425 mg/m2 i.v. bolus from day 1 to 3 every 3 weeks for a maximum of 6 cycles. The best overall response rate in an intent-to-treat analysis was 13% (2 complete responses and 2 partial responses) (95% CI, 1.2-25.5%) and 37% of patients obtained stable disease with a tumor growth control rate of 50% (95% CI, 32.1-67.9%). The median progression-free survival was 4.0 months (95% CI, 1.4-6.5 months) and median overall survival was 12.0 months (95% CI, 9.9-14.1 months). The independent prognostic factors for improved overall survival were a good performance status and a response/stabilization of disease to chemotherapy. Severe neutropenia was quite common (43.3% of patients and 14.4% of cycles), although complicated by fever only in one case (3.3% of patients). There was one toxic death. In conclusion, the study combination showed an interesting rate of tumor growth control in a cohort of patients previously treated for advanced disease with various schedules including continuous fluorouracil infusion.

Adult↗
PubMed2005

Hot-flashes in breast cancer survivors: effectiveness of low-dosage fluoxetine. A pilot study.

Breast carcinoma survivors suffering from hot-flashes experience a negative impact on their quality of life. Antidepressants have recently been proven to be effective in these women, significantly reducing the vasomotor symptoms. With this in mind, a single-arm clinical trial low-dose regimen of Fluoxetine (10 mg/day for 4 weeks) was given to twenty symptomatic breast cancer patients. Among the 12 women evaluated at the end of treatment, a statistically significant reduction of the mean number of daily hot-flashes (-36.3%, p = 0.001) and hot-flashes score (-46.2%, p = 0.0006) had been detected as compared to the baseline data. Although the dosage of Fluoxetine used in these trials was lower than earlier published, it should be noted that these positive results were achieved without any relevant side effects.

Adult↗
PubMed2004

Incidence of chemotherapy-induced amenorrhea depending on the timing of treatment by menstrual cycle phase in women with early breast cancer.

BACKGROUND: The aim of this study was to characterize the factors associated with chemotherapy-induced amenorrhea (CIA) and to examine whether the phase of the menstrual cycle at chemotherapy start could affect the rate of CIA in premenopausal women with early breast cancer. METHODS: CIA was defined as the cessation of menses for at least 3 months during or after chemotherapy. Menstrual phase was defined as days 1-6, follicular phase as days 7-14, luteal phase as days 15-20 and premenstrual phase as days 21-28. Univariate and multivariate predictors of CIA were examined. RESULTS: Among 111 premenopausal women, univariate analysis showed a higher incidence of CIA in patients treated in the follicular phase rather than in other menstrual cycle phases (67.6% compared with 45.5%; P=0.03). The rate of CIA increased with age: 65.2% and 45.8% in patients aged >42 and </=42 years, respectively (P=0.05). Upon multivariate analysis these differences remained statistically significant and duration of chemotherapy of more than six cycles correlated significantly with the incidence of CIA (P=0.03). CONCLUSIONS: The major implication of this analysis is that the timing of treatment within the menstrual cycle may potentially modulate the onset of CIA. This work and its future confirmation using prospective randomized trials would be useful in predicting the likelihood of CIA and in counseling breast cancer patients, especially those with a good prognosis who benefit less from chemical castration.

Adult↗
PubMed2004

Single-agent vinorelbine in pretreated breast cancer patients: comparison of two different schedules.

This retrospective study compared toxicity and activity of vinorelbine according to two schedules with different projected dose intensities in heavily pretreated breast cancer patients. Forty patients were assessable for toxicity and activity in each group; group A received vinorelbine 25 mg/m2 week + lenograstim (150 microg/m2 s.c. on day 3); group B received 25 mg/m2 on days 1 and 8 every 3 weeks. The projected dose intensity was 25 mg/m2/week and 16.6 mg/m2/week, and delivered dose intensity 95.2% and 94.5% in group A and B, respectively. Grade 3-4 afebrile neutropenia was recorded in 25% and 37.5% of patients in A and B, respectively. Overall response rate, 52.5% and 35%; no change, 35% and 40%; progression of disease, 12.5% and 25% in A and B, respectively. Median duration of the response was 10 months for group A and 7 months for B. Median time to progression: 9.0 months and 4.0 months for A and B, respectively. At a median follow-up of 45 months for group A and 19 months for group B, median overall survival was 19 months and 16, respectively. In conclusion the results of the study showed that dose intensity of vinorelbine could have an improvement in terms of time to progression in pretreated advanced breast cancer.

Adjuvants, Immunologic↗
PubMed2004

C-MYB, serum P-53M, genetic instability, labeling index and endoscopic findings in patients with adenoma or colorectal cancer.

Structural alterations of c-myb proto-oncogenes and serum p53 mutant level, Mitomycin C-induced chromosomal aberrations and sister chromatid exchanges and proliferative activity of mucosa (H3-thymidine -labeling index LI) are often determined to obtain more information about the diagnosis and prognosis of neoplastic and preneoplastic lesions of the colon. The aim of this study was to evaluate the endoscopic findings of a 5 year follow-up in three groups of subjects (normal, adenoma or cancer patients) and to correlate these findings with the biological alterations in the same subjects between 1990 and 1993. We analyzed 200 subjects (118 Male and 82 Female), 78 normal subjects (group A), 60 patients with adenoma (group B) and 62 with carcinoma (group C). Data regarding endoscopic lesions was collected from June 1998 to December 2000 after a 5 year follow-up and correlated with the biological alterations in the same subjects between 1990--1993. We obtained endoscopic findings from 23/137 subjects (16.8%), 6/137 (4.4%) died from other causes and 108/137 (78.8 %) were negative for lesions. The percentage of disease after 5 years is not statistically different among the three groups (groups A, B and C). There was no statistically significant association between values of the labeling index, structural alterations of c-myb, p-53-M serum levels and chromosomal aberrations and endoscopic findings in the 5 year follow-up. We conclude that the biological markers considered are not able to stratify patients in terms of risk of progression to malignant disease.

Adenoma↗
PubMed2003

Cutaneous response to irritants.

We evaluated the role of pre-existing dermatitis in the response to irritants by patch testing the skin of 40 healthy volunteers and the uninvolved skin of 480 subjects for 2 days. These latter were affected by active atopic dermatitis, psoriasis, eczema with positive and negative patch test reactions, urticaria and generalized pruritus. A first panel containing 15 micro L of aq. solutions of disodium laureth sulfosuccinate (NaLSS) 5% and 10%, potassium cocoate (KCC) 5%, potassium oleate (KOL) 5%, zinc coleth sulphate (ZnCS) 5%, sodium mireth sulphate (NaMS) 5%, sodium cocoamphoacetate (NaCCAA) 3% and 5%, was simultaneously applied to 1 site on the upper back. The results, scored by visual assessment, were compared to those observed when testing on the opposite side a second panel containing 15 micro L of aq. solutions of 3 well-known irritants, benzalkonium chloride (BAK) 1%, sodium lauryl sulphate (SLS) 1%, and dimethylsulphoxide (DMSO) 10%. Whilst the substances of the first panel and DMSO gave, on the whole, a scarce number of positive responses in all the tested groups, more evident differences in number, percent and mean intensity of the positive responses to BAK and SLS were found between the different groups. Although some of them seemed statistically significant, when the same values were evaluated by means of chi2 and Student t-test, they did not differ in a statistically significant way from the values found in healthy subjects. The results of this study seem to indicate that the substances of the first panel have a chemical structure that makes them quite safe in real-life conditions. In contrast, BAK and SLS have chemical properties that condition the number and intensity of the responses, making the role exerted by the pre-existing dermatosis quite marginal. In particular, there is no proof that the healthy skin of active atopic subjects is the most susceptible to the irritating effects of the tested substances.

Adolescent↗
PubMed2003

Phase II study of capecitabine and oxaliplatin as first-line treatment in advanced colorectal cancer.

BACKGROUND: Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer. The aim of this phase II study is to determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced non-pretreated colorectal cancer. PATIENTS AND METHODS: Forty-three chemotherapy-naïve patients were enrolled. Capecitabine 2500 mg/m(2)/day was administered orally twice a day continuously for 14 days and oxaliplatin 120 mg/m(2) was administered as a 2-h infusion on day 1, repeated every 3 weeks. RESULTS: Forty-three patients were assessable for toxicity and 39 for clinical activity: the main toxicity was grade 3 or 4 diarrhea, which occurred in 28% of the patients. The response rates were 44% [95% confidence interval (CI), 29.3% to 59.0%] and 48.7% (95% CI 33.0% to 64.4%) (intention-to-treat and per protocol analysis, respectively). The median overall survival was 20 months (95% CI 12-28). CONCLUSIONS: Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer; therefore, the capecitabine dose we utilized is probably too high. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. This combination may be preferable compared to a standard combination with infusional fluorouracil/leucovorin as it is more convenient and practical with similar efficacy. Thus, phase III trials are needed to clarify its role in the treatment of chemotherapy-naïve advanced colorectal cancer patients.

Adult↗