Activity of a specific inhibitor, gefitinib (Iressa, ZD1839), of epidermal growth factor receptor in refractory non-small-cell lung cancer.

BACKGROUND: Gefitinib (Iressa(TM), ZD1839) is an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Phase I studies showed that it is well tolerated, with evidence of tumor regression in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we aimed to assess the antitumor activity and tolerability of gefitinib in a series of patients with previously treated, advanced NSCLC, as a part of a compassionate use program. PATIENTS AND METHODS: To be eligible, all patients were required to have histologically or cytologically proven advanced or metastatic NSCLC, prior chemotherapy with at least one cisplatin-containing chemotherapy regimen or contraindication to cytotoxic drugs, Eastern Cooperative Oncology Group performance status < or =2, and adequate hematological, renal and hepatic parameters. All patients provided signed informed consent. Patient re-evaluation was performed every 4-6 weeks. RESULTS: Seventy-three consecutive patients were enrolled. Response rate, including complete and partial response, was 9.6%; an additional 43.8% of patients achieved stable disease, for an overall disease control of 53.4%. EGFR1 status was evaluated by immunocytochemistry in 25 patients. According to EGFR1 immunoreactivity all responses were observed with medium/strong imunoreactivity while three out of four responses were observed in high expressive patients. Median survival for all patients was 4 months while it reached 6 months for patients with disease control. The 1-year survival rate was 13.1% for the entire series and 23.2% for patients with disease control. Non-hematological toxicity was generally mild. CONCLUSION: Gefitinib has promising activity with a good toxicity profile in patients with progressive NSCLC who have received one or two prior chemotherapy regimens. A possible relationship within response and EGFR1 expression is suggested.

Prospective study of high-dose chemotherapy and autologous peripheral stem cell transplantation in adult patients with advanced desmoplastic small round-cell tumour.

A total of 10 desmoplastic small round-cell tumour patients were treated by high-dose chemotherapy with stem cell support. After high-dose chemotherapy, no complete response conversion was obtained and EWS-WT1 fusion transcript detection was positive in the peripheral blood during follow-up in all patients. High-dose chemotherapy did not seem to change the results in desmoplastic small round-cell tumour.

[Metastatic breast cancer: what are the objectives?]. / Il carcinoma metastatico della mammella: quali obiettivi?

UNLABELLED: The medical approach to the treatment of metastatic breast cancer has changed in the last decade since the introduction of new drugs that demonstrate high activity and better tolerability profiles. The hormonal treatment, usually considered the first choice therapy for ER-positive metastatic breast cancer patients, has seen several improvements with the discovery of new selective aromatase-inhibitor agents and pure antiestrogens. New aromatase-inhibitors have shown higher activity and fewer side effects compared to megestrol acetate in second line treatment. The first line treatment has unchanged so far, but in the next future is possible that different agents, with lower toxicity, will replace tamoxifen since studies comparing this agent with pure antiestrogens or selective aromatase-inhibitors are ongoing. These new drugs would provide a better palliation of metastatic breast cancer in terms of higher clinical benefit, tolerability and quality of life. Chemotherapy is often used in ER-negative patients or in aggressive hormone refractory disease. Randomized trials have demonstrated that anthracyclin-containing regimens were more effective than combinations without anthracyclines. New cytotoxic drugs with high activity, such as taxanes (paclitaxel and docetaxel), vinorelbine, gemcitabine and capecitabine, have been introduced. Compared with older therapies, improved objective response rates and/or improved duration of response have been reported with these newer agents alone or in combination with other drugs. However, no clear improvement of overall survival has been shown so far. Taxanos alone or in combination are today considered the second line treatment of choice and studies are assessing the value of a taxane-anthracycline containing regimen in first line treatment. Some new agents (vinorelbine) showed, alone or in combination, an interesting cost-effectiveness ratio with similar or higher "quality adjusted progression free survival" if compared to taxanes. Promising are also the results of agents that own low toxicity with comparable efficacy such as liposomal anthracycline. Attempts to improve overall survival with increased dose intensity or with high dose chemotherapy are disappointing. CONCLUSIONS: Since the goal of treatment of metastatic breast cancer is disease control rather than disease skill i.e. palliation of patients with complications of progressive cancer, the new agents have brought significant improvements (higher response rates, median time to progression, cost benefit and better tolerability). Future progresses for this disease, hopefully even in overall survival, will depend on the introduction of new therapies such as immunotherapy, inhibition of intracellular signaling, interference with tumor angiogenesis, gene-therapy and the development of vaccines.