Paclitaxel (Taxol) and carboplatin are an effective combination regimen for treating advanced breast cancer. Gefitinib (IRESSA) is the first epidermal growth factor receptor tyrosine kinase inhibitor to be approved for cancer treatment. This multicenter phase II trial treated 68 patients with advanced breast cancer with paclitaxel (175 mg/m(2) over 3 h) and 3-weekly carboplatin (area under the curve of 6) for six cycles, and 250 mg/day gefitinib orally. Median age was 57 (range 35-77) years, patients had performance status 0 (69.1%), 1 (27.9%) 2 (2.9%), 82.4% of patients had visceral metastases and 63.2% had received adjuvant chemotherapy. Forty-eight (70.6%) patients completed six cycles of chemotherapy and 20 (29.4%) patients discontinued treatment (seven [10.3%] due to disease progression, seven [10.3%] due to toxicity, five [7.4%] withdrew consent and one [1.5%] died after the first cycle). Sixty-three (92.7%) patients were evaluable for response; nine (13.2%) had complete responses, 30 (44.1%) had partial responses, 21 (30.9%) had stable disease and three (4.4%) had disease progression. Grade 3/4 adverse events in > or =5% of patients except of alopecia, included neutropenia (17.7%), anemia (10.3%), diarrhea (7.4%), thrombocytopenia (5.9%) and peripheral neuropathy (5.9%). Of those tumor biopsies available for immunohistochemical analysis (n=60), 5.0% were positive and 35.0% negative for expression of all HER-family receptors. Comparable numbers of tumor biopsies were nuclear p27(kipl) positive and negative (39.7 and 42.7%, respectively), with the majority (72.1%) negative for cytoplasmic p27(kipl). The observed efficacy data in this study were similar to those reported for the combination of paclitaxel and carboplatin alone.

The p15 gene is a putative tumor suppressor gene that encodes a member of the cyclin dependent kinase inhibitors. Inactivation of p15 by promoter hypermethylation has been postulated as a possible way by which tumor suppressor genes are inactivated in cancer. In this study, we examined the methylation status of the p15 gene promoter in 34 patients with B‐Chronic Lymphocytic Leukemia (B‐CLL), by the Methylation‐Specific Polymerase Chain Reaction. Selective methylation of the p15 gene promoter was found in 4/34 cases (11.8%). According to Rai staging, the four patients with methylated p15 were staged on diagnosis as: 1 on Stage 0, 1 in Stage I, 1 in Stage III, and 1 in Stage IV. Our results suggest that methylation of the p15 gene promoter can be detected in a small subset of B‐CLL patients, at all stages of the disease. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.

This is a retrospective analysis of 150 patients with advanced non-small cell lung cancer who had failed prior treatment or were unfit for chemotherapy and were treated with oral gefitinib ('Iressa', ZD1839; AstraZeneca) 250 mg/day. Thirty-two patients who received gefitinib for 3 weeks or less were not included in the analysis. For the remaining 118 evaluable patients, the mean age was 63.1 years; most patients had received prior chemotherapy (97.5%), Eastern Cooperative Oncology Group performance status scores 0-2 (97.4%) and stage IV disease (64.4%). The majority were symptomatic (84.6%). Disease control was observed in 30 patients (25.4%), of whom five had a partial response and 25 had stable disease; 18 (15.3%) were not evaluable. Median duration of treatment was 29.9 weeks in responding patients and 11.5 in patients with progressive disease (p<0.0001). Median overall survival was 7.3 months (15.2 months for disease control) and median progression-free survival was 3.2 months. Gefitinib was well tolerated, with grade 3/4 skin rash and diarrhea seen in 2.5 and 4.2% of patients, respectively. Clinical benefit was evaluated using questionnaires before and following treatment with gefitinib. In 82 patients with completed questionnaires, evaluation revealed symptom improvement in 40.1% and improvement in general feeling in 31.4%. Epidermal growth factor receptor (EGFR) analysis found that efficacy did not correlate with tumor EGFR overexpression. Therefore, in this retrospective analysis, gefitinib treatment provided disease control in 25% of patients who derived significant palliative benefit.