S. Agelaki

Cytokeratin-19 mRNA-Positive Circulating Tumor Cells After Adjuvant Chemotherapy in Patients With Early Breast Cancer

PURPOSEnTo evaluate the prognostic significance of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in peripheral blood of women with early-stage breast cancer after the completion of adjuvant chemotherapy.nnnPATIENTS AND METHODSnBlood was obtained from 437 patients with early breast cancer before the start and after the completion of adjuvant chemotherapy, and the presence of CK-19 mRNA-positive CTCs was assessed by real-time reverse transcriptase polymerase chain reaction. Interaction with known prognostic factors and association of CTCs with clinical outcome were investigated.nnnRESULTSnCK-19 mRNA-positive CTCs were detected before chemotherapy in 179 patients (41.0%). After adjuvant chemotherapy, a significant change in CK-19 status was observed, as status for 51% of patients with initially CK-19 mRNA-positive disease turned negative, and status for 22% of patients with initially CK-19 mRNA-negative disease became positive (McNemar test P = .004). The detection of CK-19 mRNA-positive CTCs postchemotherapy was associated with involvement of more than three axillary lymph nodes (P = .026). Clinical relapses and disease-related deaths were significantly increased in patients with detectable postchemotherapy CK-19 mRNA-positive CTCs (both P < .001, respectively). Disease-free and overall survival were significantly reduced in patients with detectable CK-19 mRNA-positive CTCs postchemotherapy (P < .001 and P = .001, respectively). In multivariate analysis, the detection of CK-19 mRNA-positive CTCs before and after adjuvant chemotherapy was an independent factor associated with reduced disease-free survival (P < .001) and overall survival (P = .003).nnnCONCLUSIONnThe detection of CK-19 mRNA-positive CTCs in the blood after adjuvant chemotherapy is an independent risk factor indicating the presence of chemotherapy-resistant residual disease.

Non-Platinum-Based First-Line Followed by Platinum-Based Second-Line Chemotherapy or the Reverse Sequence in Patients with Advanced Non-Small Cell Lung Cancer: A Retrospective Analysis by the Lung Cancer Group of the Hellenic Oncology Research Group

Background: Non-platinum-containing regimens have been proposed as alternatives to platinum-based doublets in the first-line treatment of patients with non-small cell lung cancer (NSCLC). However, conflicting results about their equivalence have been reported. Methods: We reviewed the records of patients enrolled in randomized controlled first-line trials conducted by the Hellenic Oncology Research Group from February 1997 to September 2006. The outcome of patients treated with first-line non-platinum-based chemotherapy who received platinum-based chemotherapy upon progression (cohort A) or platinum-based first-line chemotherapy followed by non-platinum-containing second-line chemotherapy (cohort B) was retrospectively analyzed. Results: Two-hundred and sixty-seven patients were identified in cohort A, and 123 in cohort B. Median follow-up time was 12.5 and 15.7 months for cohorts A and B. A significantly higher response rate and time to tumor progression (TTP) was recorded for patients treated with platinum-based compared to those receiving non-platinum-based first-line chemotherapy (45.5 vs. 21.3%, p < 0.0001 and 5.8 vs. 3.1 months, p= 0.002, respectively). Platinum-based regimens administered as second-line treatment resulted in a 13.1% response rate. TTP for second-line chemotherapy did not differ significantly between the two cohorts. Median overall survival was 13.3 and 15.7 months for cohorts A and B (p = 0.538). Conclusion: Both sequences resulted in similar efficacy in terms of overall survival. Encouraging median survival was achieved for selected patients with NSCLC who received both first- and second-line chemotherapy.

Vinorelbine metronomic plus bevacizumab as salvage therapy for patients with metastatic breast cancer (MBC): A multicenter phase II study.

1133 Background: Continuous administration of low dose oral vinorelbine, given three times a week (metronomic) is feasible and exceptionally well tolerated. Early results show activity against refractory tumors and provide evidence towards clinical proof of efficacy for metronomic chemotherapy. Recently, initial therapy of metastatic breast cancer (MBC) with paclitaxel plus bevacizumab demonstrated prolonged progression-free survival, as compared with paclitaxel alone. In this study vinorelbine metronomic and bevacizumab was evaluated as salvage therapy in women with MBC. Methods: Eligible patients with MBC had ≥1 prior chemotherapy regimens and ECOG PS ≤2. Patients received vinorelbine p.o. (50 mg 3 times a week) and iv bevacizumab 10 mg/kg every 14 days. Therapy was continued until disease progression or the appearance of unacceptable toxicity. The primary endpoint was objective response rate (ORR). We report the results of a preplanned analysis in 13 evaluable patients. Results: The median age of the p...

A Dose Escalation Study of Biweekly Oral Vinorelbine and Gemcitabine in Patients with Solid Tumors

Purpose: To determine the maximum tolerated doses (MTDs) and the dose-limiting toxicities of a biweekly administration of oral vinorelbine and gemcitabine in patients with advanced solid tumors. Patients and Methods: Twenty-eight patients with advanced stage solid tumors were enrolled, and 12 (42.9%) of them were chemotherapy naive. Escalating doses of vinorelbine (50–70 mg/m2 per os) and gemcitabine (800–1,000 mg/m2 as a 30-min intravenous infusion) were administered on days 1 and 15 in 4-week cycles. Results: MTDs were reached at 70 mg/m2 p.o. for vinorelbine and 900 mg/m2 for gemcitabine. Grade 4 neutropenia, febrile neutropenia, grade 4 nausea/vomiting and treatment delay due to grade 3 neutropenia were the dose-limiting events during the first cycle of chemotherapy. A total of 94 chemotherapy cycles were administered with only one episode of febrile neutropenia and no toxic deaths. Severe (grade 3–4) neutropenia occurred in 10% of cycles while non-hematological toxicity was mild with grade 2–3 asthenia occurring in 17 (18%) cycles. Objective responses were achieved in patients with prostate and non-small cell lung cancer. Conclusions: The combination of biweekly oral vinorelbine (70 mg/m2) and gemcitabine (900 mg/m2) is a well-tolerated regimen with promising results in patients with advanced solid tumors.