Biomedical subjects

Andrea Sartore-Bianchi

Publications and source records attributed to Andrea Sartore-Bianchi.

6 recordsLinked to original sources

PubMed2005

Raltitrexed-Oxaliplatin combination chemotherapy is inactive as second-line treatment for malignant pleural mesothelioma patients.

Within a single-institution phase II trial, we investigated the antitumor activity of the Raltitrexed-Oxaliplatin combination as second-line therapy for malignant pleural mesothelioma (MPM). Fourteen patients were enrolled and all were assessable for response. The trial was then closed because chemotherapy, though well tolerated, yielded no objective responses. The best response observed was disease stabilization in 4 patients only (28.57%), while the other 10 patients (71.42%) progressed despite treatment. Median time to progression (TTP) was 8 weeks (average: 9.85, range: 7-20), while median overall survival was just 14 weeks (average: 21.69, range: 9-66+).

Adult↗

PubMed2005

Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study.

BACKGROUND: The antiepidermal growth factor receptor (antiEGFR) monoclonal antibodies cetuximab and panitumumab have good clinical activity in about 10% of patients with metastatic colorectal cancer that is resistant to chemotherapy. The molecular mechanisms underlying clinical response or resistance to these agents are unknown. METHODS: Tumours from 31 patients with metastatic colorectal cancer who had either an objective response (n=10) or stable disease or progressive disease (n=21) after treatment with cetuximab or panitumumab were screened for genetic changes in EGFR or its immediate intracellular effectors. Specifically, we assessed the EGFR copy number and the mutation profile of the EGFR catalytic domain and of selected exons in KRAS, BRAF, and PIK3CA. RESULTS: Eight of nine of patients with objective responses who were assessable by fluorescence in-situ hybridisation (FISH) had an increased EGFR copy number. By contrast, one of 21 non-responders assessable by FISH had an increased EGFR copy number (p<0.0001 for responders vs non-responders, Fisher's exact test). The mutation status of the EGFR catalytic domain and its immediate downstream effectors PIK3CA, KRAS, and BRAF did not correlate with disease response. In colorectal-cancer cell lines, the concentration of cetuximab that completely inhibited proliferation of cells with amplified EGFR copy number did not affect proliferation of cells with unamplified EGFR. INTERPRETATION: We propose that the response to antiEGFR treatment has a genetic basis and suggest that patients might be selected for treatment on the basis of EGFR copy number.

Aged↗

PubMed2005

Pro-neoangiogenic cytokines (VEGF and bFGF) and anemia in solid tumor patients.

Using a commercial ELISA assay, we evaluated circulating VEGF and bFGF levels in 203 consecutive patients with solid tumors, and sought a correlation between them and with the grade of anemia. Serum VEGF values were within the normal range in 128 patients (63.05%), with a mean value of 675.04 pg/ml (median, 571.00; range, 0-2796.54). The analysis of VEGF values per tumor group did not provide any statistically significant difference. Regarding bFGF, 143 patients (70.44%) had measurable, and thus abnormal, bFGF values. Overall, mean bFGF serum value was 57.14 pg/ml (median, 8.30; range, 0-4334.71), with the highest bFGF levels found in breast carcinoma patients. As expected, a large number of our patients was fairly anemic, mean hemoglobin level being 11.47 g/dl (median, 11.30; range, 7.1-19.20), the lowest titers being observed in prostate carcinoma patients. No statistically significant correlation was found between serum VEGF and hemoglobin values (r=0.004) but a significant negative correlation was seen between serum bFGF and hemoglobin (r=-0.22, p<0.05). Considering the different tumor groups, a statistically significant negative correlation between bFGF and hemoglobin becomes even more apparent in the subgroup of renal carcinoma patients (r=-0.55, p<0.05). In conclusion, our results demonstrate that there is a statistically significant correlation between systemic hypoxia (evaluated in terms of hemoglobin levels) and circulating bFGF values, but not VEGF; this correlation may lead to therapeutic interventions.

Aged↗

PubMed2004

Gemcitabine and oxaliplatin in the treatment of patients with immunotherapy-resistant advanced renal cell carcinoma: final results of a single-institution Phase II study.

BACKGROUND: Currently, there is no standard treatment for patients with advanced renal cell carcinoma (RCC) who do not experience a response to first-line immunotherapy. In the current Phase II study, the authors explored the antitumor activity of a combination of gemcitabine and oxaliplatin (L-OHP) in this setting. METHODS: Forty-two patients with RCC who had progressive disease following immunotherapy received gemcitabine (1000 mg/m2 intravenously on Days 1 and 8 every 21 days) and L-OHP (90 mg/m2 intravenously on Day 1 every 21 days) for a minimum of 2 cycles before responses were evaluated. Responses to treatment and toxicity were recorded according to the Response Evaluation Criteria in Solid Tumors and the National Cancer Institute Common Toxicity Criteria, respectively. RESULTS: No complete responses were recorded; however, 6 patients experienced a partial response (14.28%; 95% confidence interval, 5.43-28.5%), 11 patients (26.19%) had temporary stable disease as a best response, and the remaining 25 patients (59.52%) experienced progression despite receiving treatment. The median time to disease progression was 2.5 months (mean, 3.86 months; range, 1.5-11.0 months), whereas the median overall survival was 9.5 months (mean, 10.46 months; range, 4.0-22.5 months). With regard to toxicity, treatment generally was well tolerated, with only one episode of Grade 4 toxicity and expected episodes of Grade 3 toxicity, including myelosuppression and neuropathy. CONCLUSIONS: The current results suggest that the combination of gemcitabine and L-OHP possesses a certain level of activity and an acceptable toxicity profile in patients with immunotherapy-resistant advanced RCC.

Adenocarcinoma, Clear Cell↗

PubMed2004

Low doses of subcutaneous interleukin-2 plus interferon-alpha do not induce thyroid function alterations in advanced renal cell carcinoma patients.

The incidence of thyroid function changes among renal cell carcinoma (RCC) patients treated with high-dose IL-2 plus IFN-alpha ranges from 9 to 59%, independently of the administration route (i.v. or s.c.) of IL-2. Although several studies demonstrated a correlation between high-dose IL-2/IFN-alpha regimens and autoimmune thyroid disease, only very limited data are available when low doses of IL-2 plus IFN-alpha are used. We prospectively studied thyroid function in 52 patients with metastatic RCC undergoing immunotherapy with low-dose IL-2 + IFN-alpha. All patients received treatment cycles consisting of both s.c. IL-2 and i.m. IFN-alpha for 4 consecutive weeks; cycles were repeated at 4-month intervals in all patients, irrespectively of their response. Thyroid stimulating hormone (TSH), 3,3',5-triiodo-L-thyronine (T3), thyroxine (T4), human anti-thyroglobulin antibodies (hTg-Ab) and human anti-thyroid peroxidase antibodies (hTPO-Ab) were assayed in all patients before and after each of the first 3 cycles. None of the patients showed clinical signs of dysthyroidism, nor required replacement or suppressive treatment on thyroid function; specifically, no statistically significant differences were found when the median pre- and post-treatment TSH, T3, T4, hTg-Ab and hTPO-Ab levels of each cycle were compared. The median TSH values after the 3 cycles were, respectively, 1.06 [Inter Quartile Range (IQR) 0.58-1.51], 1.21 (IQR 0.58-1.51) and 1.05 micro U/ml (IQR 0.67-1.73). As for thyroid hormones, median values after each of the 3 cycles were: 1.38 (IQR 1.19-1.50), 1.46 (IQR 1.17-1.66) and 1.36 (IQR 1.16-1.46) ng/ml for T3, and 8.74 (IQR 7.26-9.45), 8.67 (IQR 7.12-9.18) and 8.40 (IQR 7.12-9.33) micro g/dl for T4. These data show that a regimen of low-dose IL-2 plus IFN-alpha does not seem to affect thyroid function, neither inducing signs or symptoms of dysthyroidism, nor by causing major biochemical changes in TSH and thyroid hormone levels, or an increase in thyroid-specific auto-antibodies.

Adjuvants, Immunologic↗

PubMed2002

Intrapleural interleukin-2 induces nitric oxide production in pleural effusions from malignant mesothelioma: a possible mechanism of interleukin-2-mediated cytotoxicity?

Due to the frequent use of intrapleural interleukin-2 (IL-2) to treat pleural effusions from malignant mesothelioma (MMe), we measured nitric oxide (NO) end product nitrite (NO(2)(-)) in pleural effusions of 12 MMe patients with chronic or chronic-relapsing pleurisy. Through high performance liquid chromatography analysis, NO(2)(-) was found in the initial pleural fluid sample of all patients (156.25 pmol ml(-1)), and increased significantly following IL-2 intrapleural instillation, both at 24 (589.91 pmol ml(-1), P < or = 0.0005) and 48 h (756 pmol ml(-1), P< or = 0.0005). Even though it is difficult to argue if the large amounts of NO end product NO(2)(-) we observed is produced by IL-2-stimulated and recruited immune cells, by MMe cells themselves, or by both, it is possible that NO could contribute to the complex antitumor activity of IL-2.

Aged↗