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Biomedical subjects

Luca Gianni

Publications and source records attributed to Luca Gianni.

6 recordsLinked to original sources

International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations.

Primary systemic therapy (PST) represents the standard of care in patients with locally advanced breast cancer. In addition, there is increasing information on PST in operable breast disease that supports the use of PST in routine practice. However, current regimens and techniques vary. To address this concern, a group of representatives from breast cancer clinical research groups in France, Germany, Italy, the United Kingdom, and the United States reviewed all available data on prospective randomized trials in this setting. Recommendations are made regarding terminology, indications, regimen, diagnosis before treatment, monitoring of efficacy, tumor localization, surgery, pathologic evaluation, and postoperative treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Cardiotoxic effects of anthracycline-taxane combinations.

The association of doxorubicin (DOX) and paclitaxel (PTX) is very active in breast cancer. Unfortunately, PTX may potentiate the cardiotoxic effects of anthracyclines: it causes nonlinear disposition of DOX and its metabolites, leading to persistant of elevated plasma concentrations of the anthracyclines. However, this pharmacokinetic interference is not sufficient to explain the enhanced cardiotoxicity of the combination. Recent data suggest that PTX stimulates the conversion of DOX to cardiotoxic metabolites (namely doxorubicinol) inside cardiomyocytes. Docetaxel (DTX) does not have a major influence on DOX plasma concentration because it does not interfere with its elimination. Clinical data suggest that DTX may not enhance anthracycline cardiotoxicity, but patients seldom received a total anthracycline dose compatible with increased risk. Furthermore, there are experimental data indicating that DTX can also stimulate the metabolism of DOX to toxic species in human heart.

Anthracyclines↗

Improvements in quality of life and disease-related symptoms in phase I trials of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in non-small cell lung cancer and other solid tumors.

PURPOSE: The feasibility and utility of assessing quality of life (QoL) and disease-related symptoms in patients with advanced cancer have been evaluated in two Phase I clinical trials of p.o. administered ZD1839 ('Iressa'), an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced cancer. EXPERIMENTAL DESIGN: Functional Assessment of Cancer Therapy (FACT) questionnaires, including disease-specific subscales for lung, head and neck, colorectal, prostate, and ovarian cancer, were completed by patients in two open-label, Phase I, escalating multiple-dose safety and tolerability trials. RESULTS: In 157 patients, 92% of whom had received prior therapy, compliance in returning FACT questionnaires was 87% (European/Australian trial) and 57% (United States trial). This did not appear to be influenced by dose level or tumor type. For patients with colorectal, prostate, or ovarian cancer, median QoL [FACT and Trial Outcome Index (TOI)] scores deteriorated over time. In contrast, for patients with non-small cell lung cancer (NSCLC) or head and neck cancer, median FACT and TOI scores did not deteriorate significantly, and in the United States trial, head and neck cancer scores improved significantly over time. In patients with NSCLC, symptom-related scores measured by the Lung Cancer Subscale of FACT-L appeared sensitive to clinical change. CONCLUSIONS: QoL (FACT-L) questionnaires were used successfully in the Phase I clinical trials of ZD1839. They appeared to be a sensitive tool to monitor clinical changes for the five tumor types in these trials and showed that ZD1839 has the potential to improve patients' QoL.

Administration, Oral↗

The future of targeted therapy: combining novel agents.

The anti-HER2 monoclonal antibody Herceptin demonstrates significant clinical benefits in patients with HER2-positive metastatic breast cancer (MBC). However, the combination of Herceptin plus anthracyclines, although efficacious, demonstrated a higher than expected incidence of cardiotoxicity. Therefore, studies are currently investigating Herceptin in combination with alternative anthracyclines, such as epirubicin and liposomal doxorubicin. Investigators are also beginning to examine the potential of Herceptin plus hormonal therapy, a combination that will delay the need to use cytotoxic chemotherapy. Furthermore, a plethora of novel agents have been developed that target the processes of tumorigenesis, including HER1 tyrosine-kinase inhibitors, farnesyl-transferase inhibitors, and cyclooxygenase 2 (COX2) inhibitors. Preclinical data demonstrate that the combination of Herceptin with these agents can produce at least additive effects and therefore a rationale exists to investigate these regimens in the clinical setting. As a result of the targeted nature of these agents, it is anticipated that such strategies will have favorable safety profiles. It is possible that through the development and use of biological anticancer agents, such as Herceptin, future anticancer regimens may be specifically tailored to each patient based on their molecular characteristics.

Antibiotics, Antineoplastic↗

Anthracyclines.

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Animals↗