Merkel cell carcinoma of the skin: a retrospective study of 24 cases by the Hellenic Cooperative Oncology Group.

BACKGROUND: The purpose of this retrospective study was to present the epidemiological and clinical characteristics of 24 patients with Merkel cell carcinoma of the skin (MCC) and their response to various therapeutic modalities. METHODS: The tumor registry of the Hellenic Cooperative Oncology Group was used to identify patients with MCC diagnosed between 1986 and 2006. RESULTS: The most frequent primary sites were the extremities (50%), followed by the head (33%) and the trunk (17%). Median time of follow-up was 24 months. Sixteen patients were initially diagnosed with stage I, 5 patients with stage II, and 3 patients with stage III (metastatic) disease. Six patients with stage I disease received adjuvant chemotherapy (CT) and/or radiotherapy (RT). All patients with stage I disease treated only with surgery relapsed, whereas 33% of the patients treated with adjuvant therapy recurred. All patients with stage II disease received adjuvant treatment. Among them, 2 patients relapsed. Disease-free survival (DFS) and overall survival (OS) did not differ significantly between patients with stage I and II disease (stage I: 4-year DFS 27%, 4-year OS 56%; stage II: 4-year DFS 60%, 4-year OS 80%). Patients treated with adjuvant therapy had significantly better DFS than those treated only with surgery (p = 0.012), but OS did not differ significantly (adjuvant group: 4-year DFS 59%, 4-year OS 74%; surgery group: 4-year DFS 10%, 4-year OS 50%). Eleven patients with locally advanced or metastatic disease received CT. The response rate was 73% (complete remission 18%), median progression-free survival was 10 months and median OS was 14 months. Complete remission was achieved in 2 other cases, with the addition of RT after CT. CONCLUSIONS: MCC is an aggressive neoplasm with significant chemosensitivity and radiosensitivity, but poor outcome. The role of adjuvant treatment should be further investigated.

A modified mutagenic PCR-RFLP method for K-ras codon 12 and 13 mutations detection in NSCLC patients.

Evidence from many investigators has shown that mutations in the first exon of K- ras gene occur at elevated frequencies in lung, pancreatic and colon carcinoma and seem to be of prognostic importance. The aim of this study was to develop an effective method for the detection of K- ras mutations in codons 12 and 13 in non-small-cell lung cancer (NSCLC) patients in order to investigate correlation with clinical outcome. DNA was extracted from tumour and neighbouring non-neoplastic lung tissues from 70 patients and screened for codon 12 and 13 mutations. We applied a mutagenic PCR-restriction fragment length polymorphism for both codon 12 and 13 mutation detection. Codon 12 mutation was identified in 20% of NSCLC patients, whereas no codon 13 mutation was detected. As expected, the respective non-neoplastic tissues exhibited no mutations. We observed an increased codon 12 mutation prevalence in adenocarcinoma comparing to other types of carcinomas. Follow-up for 29 patients with a mean time of 12 months indicates an increased relapse rate in NSCLC patients with the K- ras codon 12 mutation. Furthermore, a trend towards increased percentage of mutant samples was observed in the advanced stage group of patients. We provide evidence that our approach is a fast and reliable method for screening K- ras exon 1 mutations in tumour samples from NSCLC patients.

Gemcitabine and vinorelbine as second-line treatment in patients with metastatic breast cancer progressing after first-line taxane-based chemotherapy: a phase II study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: Gemcitabine and vinorelbine have shown activity in breast cancer. A phase II trial was initiated in order to evaluate the response rate (RR) and time to progression (TTP) of the combination of the two drugs in patients with metastatic breast cancer progressing after first-line taxane-based chemotherapy. PATIENTS AND METHODS: Thirty-one patients were treated with the combination of gemcitabine 1000 mg/m2 days 1 + 8 and vinorelbine 30 mg/m2 days 1 + 8. The cycles were repeated every three weeks. RESULTS: Of 27 evaluable patients 1 (4%, 95% confidence interval (95% CI): 0.1%-19%) achieved complete remission (CR), five (18%; 95% CI: 6%-38%) partial remission (PR), eleven (40%; 95% CI: 22%-61%) stable disease and ten patients progressed. The median duration of response was six months (range 4-10+) and the median duration of disease stabilization was five months (range 2-22+). With a median follow-up of 16 months (range 0.4-22+) the median TTP was 3.5 months (range 0.4-22+) and the median survival was 9.5 months (range 0.4-22+). Grade 3-4 toxicities were granulocytopenia 15 patients (48%), rash 3 patients (10%), neuropathy 1 patient (3%) and thrombocytopenia 1 patient (3%). In conclusion the combination of gemcitabine/vinorelbine in the doses administered in this group of patients had a response rate of 22% and needs to be further evaluated in metastatic breast cancer.

Paclitaxel and carboplatin as first-line chemotherapy for advanced breast cancer.

In a phase II study, 66 patients with advanced breast cancer (median age 56 years; range, 28 to 75 years) were treated with paclitaxel (Taxol), 175 mg/m2 infused over 3 hours, and carboplatin (Paraplatin), dosed to attain an area under the concentration-time curve (AUC) of 6 mg x min/mL; treatment was repeated every 3 weeks. A total of 38 (58%) patients had received prior adjuvant chemotherapy, 21 with a regimen containing an anthracycline or mitoxantrone (Novantrone). As of May 1997, 295 cycles of paclitaxel-carboplatin have been administered, 248 (84%) at full dose. The relative dose intensity of paclitaxel is 0.9 (range, 0.5 to 1.2). Of the 66 patients, 8 (12%) have achieved a complete response and 27 (41%) a partial response, for a total response rate of 53%. Grade 3 to 4 toxicities have included anemia (5%), leukopenia (25%), thrombocytopenia (5%), nausea/vomiting (7%), myalgias/arthralgias (4%), allergic reaction, neurotoxicity, and infection (2% each). Alopecia has been universal. Median time to progression is 8.9 months; median survival has not yet been reached. We conclude that the combination of paclitaxel and carboplatin has significant activity in advanced breast cancer and can easily be administered on an outpatient basis with manageable toxicity.

Prognostic variables in greek patients with stage II breast cancer: a Hellenic Cooperative Oncology Group study.

The independent effects of several patient, tumor and treatment-related prognostic factors on relapse-free survival (RFS) and overall survival (OS) were assessed by Cox multivariate regression analysis in 988 Greek patients with stage II breast cancer. At a median follow-up time of 83 (range 3.3-131+) months and after the evaluation of all patients together, the number of positive axillary nodes (p < 0.0001), tumor size (p = 0.0024) and tumor grade (p = 0.0008) were identified as significant prognostic factors for RFS. Also, the number of positive nodes (p < 0.0001), tumor size (p = 0.0002) and ER status (p = 0.0001) were found to be significant for OS. These short-term prognostic variables are similar to those reported for this group of patients in other European countries and in the USA.