Cardiac safety, efficacy, and correlation of serial serum HER2-extracellular domain shed antigen measurement with the outcome of the combined trastuzumab plus CMF in women with HER2-positive metastatic breast cancer: results from the EORTC 10995 phase II study.

PURPOSE: Cardiotoxicity is a side effect of trastuzumab. We assessed efficacy and cardiac safety of CMF with trastuzumab (CMF+T) in HER2-positive metastatic breast cancer patients (MBC). METHODS: In this phase II study, centrally confirmed, previously treated HER2-positive MBC patients with measurable disease (per RECIST v 1.0) were enrolled. Initially, patients were randomized between 8 CMF cycles alone or combined with trastuzumab during chemotherapy, followed by 3-weekly trastuzumab maintenance till progression. A protocol amendment dropped the CMF arm and thereafter all patients received CMF+T. Translational research for prediction of treatment benefit was performed through serial serum HER2-shed antigen assessments. RESULTS: Ninety patients (CMF: 19; CMF+T: 71) were enrolled between 2002 and 2006. Median age was 54 years. 42 patients had prior chemotherapy (33 with anthracyclines) and 41/71 patients who received CMF+T continued trastuzumab monotherapy for a median duration of 40 weeks. Overall response rate was 50% for CMF+T (35/70) and 32% for CMF (6/19). Median duration of response was 10.3 months and 5.4 months, respectively. Median progression-free survival was 9.4 months (95% CI 8.1-11.6) and 4.8 months (95% CI 2.8-7.9), respectively. In the CMF+T arm, 13(18%) patients had an absolute LVEF decline, including 3 patients developing any grade of New York Heart Association cardiac dysfunction. Patients with an increase of 30% over baseline shed antigen had a higher progression risk (95% CI 7.6, 3.9-14.8). CONCLUSIONS: CMF+T is effective, with an acceptable cardiotoxicity profile. LVEF declines were mostly asymptomatic and occurred irrespective of previous anthracycline exposure. CMF+T can be considered for these patients, if other cytotoxics are contraindicated.

Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study.

PURPOSE: To compare the efficacy of a standard anthracycline-based regimen to a dose-intensified anthracycline regimen in locally advanced breast cancer. PATIENTS AND METHODS: Locally advanced breast cancer patients were randomly assigned onto a study comparing cyclophosphamide (C; 75 mg/m(2) orally days 1 to 14), epirubicin (E; 60 mg/m(2) intravenously [IV] days 1, 8), and fluorouracil (F; 500 mg/m(2) IV days 1, 8) six cycles every 28 days versus E (120 mg/m(2) IV day 1), C (830 mg/m(2) IV day 1), and granulocyte colony-stimulating factor (filgrastim; 5 micro g/kg/d subcutaneously days 2 to 13) six cycles every 14 days. The study was designed to detect a 15% improvement; that is, from 50% to 65% in median progression-free survival (PFS) in favor of the dose-intensified regimen. RESULTS: A total of 448 patients were enrolled over a period of 3 years. The median dose intensity delivered for C and E reached, respectively, 85% and 87% of that planned in the CEF arm and 96% and 95% of that planned in the EC arm. The dose-intensified arm was slightly more emetogenic and generated more grade 3 to 4 anemia but less febrile neutropenia episodes. After a median follow-up of 5.5 years, 277 events have been reported. The median PFS was 34 and 33.7 months for CEF and EC, respectively (P =.68), and the 5-year survival rate was 53% and 51% for CEF and EC, respectively (P =.94). CONCLUSION: Dose-intensified EC does not provide a measurable therapeutic benefit over CEF as neoadjuvant chemotherapy for unselected locally advanced breast cancer patients.

An epidermal growth factor receptor intron 1 polymorphism in healthy women in Poland.

The frequency of CA allele combinations was assessed in healthy women from Poland and compared to previously published polymorphism data of individuals from Germany and a Caucasian reference group. There were close similarities between these three geographically and ethnically similar populations. By contrast, the distribution of these alleles in European and Asian (Japan) populations proved to be different. There might therefore be major ethnic differences in allelic frequencies of EGFR intron 1 polymorphism. Our results provide new data on EGFR microsatellite instability and may contribute to the understanding of EGFR gene expression regulation. The clinical relevance of these findings warrants further evaluation.

The occurrence of cerebellar hemangioblastoma in numerous first degree relatives with von Hippel-Lindau disease.

Von Hippel-Lindau disease is an autosomal dominant disorder caused by a mutation of VHL gene. The incidence of the disease is one in 36,000 and its clinical manifestation is a familial occurrence of hemangioblastoma of the central nervous system and retina, renal cell cancer and pheochromocytoma. Cerebellar hemangioblastoma is the most frequent or sometimes the only abnormality observed in this syndrome. We present a family with von Hippel-Lindau disease in which four first degree relatives had a cerebellar hemangioblastoma. This neoplasm caused the death of two brothers aged 27 and 24 years old, respectively and their mother aged 62. The third son of this family was affected ten years ago, at the age of 30. The healthy family members are counselled in Oncological Genetic Outpatient Unit in Gdansk.

[Analysis of prognostic factors for long term survival in patients with small cell lung cancer]. / Analiza czynników rokowniczych warunkujacych dlugotrwale przezycia chorych na drobnokomórkowego raka pluca.

Prognostic factors for long term survival were analyzed in a group of 719 patients with small cell lung carcinoma treated within 4 consecutive prospective multicenter trials between 1981 and 1990. 74 patients (10.3%) survived more than 2 years; 30 of them (4.2%) with no evidence of disease. The most significant determinator of prolonged survival was extent of disease: 13.9% (59/424) of patients with limited disease vs. 5.1% (15/295) with extensive disease survived more than 2 years (p < 0.001). Of 138 female patients 24 (17.4%) were long term survivors, compared to 8.6% (50/581) of males (p < 0.01). Initial good performance status and no weight loss were also found to be correlated with long term survival. Of the group of 2-year survivors 51 patients subsequently died (median survival duration 31 months), 10 are alive with cancer or are lost to follow up and 13 are in complete remission with median follow up of 64 months. 20 patients (3.8%) survived more than 5 years. This study confirms the possibility of cure in SCLC, especially in patients with favorable prognostic factors.

Quality indicators in breast cancer care.

To define a set of quality indicators that should be routinely measured and evaluated to confirm that the clinical outcome reaches the requested standards, Eusoma has organised a workshop during which twenty four experts from different disciplines have reviewed the international literature and selected the main process and outcome indicators available for quality assurance of breast cancer care. A review of the literature for evidence-based recommendations have been performed by the steering committee. The experts have identified the quality indicators also taking into account the usability and feasibility. For each of them it has been reported: definition, minimum and target standard, motivation for selection and level of evidence (graded according to AHRO). In overall 17 main quality indicators have been identified, respectively, 7 on diagnosis, 4 on surgery and loco-regional treatment, 2 on systemic treatment and 4 on staging, counselling, follow-up and rehabilitation. Breast Units in Europe are invited to comply with these indicators and monitor them during their periodic audit meetings.

An epidermal growth factor receptor intron 1 polymorphism in healthy women in Poland.

The frequency of CA allele combinations was assessed in healthy women from Poland and compared to previously published polymorphism data of individuals from Germany and a Caucasian reference group. There were close similarities between these three geographically and ethnically similar populations. By contrast, the distribution of these alleles in European and Asian (Japan) populations proved to be different. There might therefore be major ethnic differences in allelic frequencies of EGFR intron 1 polymorphism. Our results provide new data on EGFR microsatellite instability and may contribute to the understanding of EGFR gene expression regulation. The clinical relevance of these findings warrants further evaluation. (Int J Biol Markers 2005; 20: 184-8).