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Biomedical subjects

Jan B Vermorken

Publications and source records attributed to Jan B Vermorken.

7 recordsLinked to original sources
PubMed2003

Comparison of the sulforhodamine B assay and the clonogenic assay for in vitro chemoradiation studies.

PURPOSE: Since there is a growing interest in preclinical research on interactions between radiation and cytotoxic agents, this study focused on the development of an alternative to the very laborious clonogenic assay (CA). METHODS: The colorimetric sulforhodamine B (SRB) assay was compared to the clonogenic assay for radiosensitivity testing in two lung cancer cell lines (A549, H292), one colon cancer cell line (HT-29) and one breast cancer cell line (MCF-7). In addition, the combination of the radiosensitizing agent gemcitabine and radiation was investigated with both assays. RESULTS: The dose-response curves obtained with the SRB assay and the CA were very similar up to 6 Gy. The radiosensitivity parameters (SF(2), alpha, beta, MID and ID(50)) obtained from the SRB assay and the CA were not significantly different between H292, A549 and MCF-7 cells. The radiation dose-response curves for A549 and H292 cells pretreated with 4 n M gemcitabine for 24 h clearly showed a radiosensitizing effect with both assays. The dose-enhancement factors obtained with the SRB assay and the CA were 1.80 and 1.76, respectively, for A549 cells, and 1.52 and 1.41 for H292 cells. CONCLUSIONS: The SRB assay was shown to be as useful as the more traditional CA for research on chemotherapy/radiotherapy interactions in cell lines with moderate radiosensitivity. This assay will be used for more extensive in vitro research on radiosensitizing compounds in these cell lines.

Breast Neoplasms↗
PubMed2003

International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma.

BACKGROUND: Adjuvant chemotherapy has been suggested as a possible strategy to improve survival in women with early-stage ovarian cancer; however, all randomized studies to date have been too small to answer this question reliably. METHODS: We performed a preplanned combined analysis of two parallel randomized clinical trials (International Collaborative Ovarian Neoplasm 1 [ICON1] and Adjuvant ChemoTherapy In Ovarian Neoplasm [ACTION]) in early-stage ovarian cancer that compared platinum-based adjuvant chemotherapy with observation following surgery. Between November 1990 and January 2000, 925 patients (477 in ICON1 and 448 in ACTION) who had surgery for early-stage ovarian cancer were randomly assigned to receive platinum-based adjuvant chemotherapy (n = 465) or observation (n = 460) until chemotherapy was indicated. Kaplan-Meier analysis was used to compare overall and recurrence-free survival by treatment allocation. In subgroup analyses of pretreatment age, tumor stage, histologic cell type, and differentiation grade, the differences in relative size of effect were tested using a chi-square test for interaction or a chi-square test for trend. All tests of statistical significance were two-sided. RESULTS: After a median follow-up of over 4 years, 245 patients had died or had a recurrence (ICON1: 133, ACTION: 112). Overall survival at 5 years was 82% in the chemotherapy arm and 74% in the observation arm (difference = 8% [95% confidence interval (CI) = 2% to 12%]; hazard ratio [HR] = 0.67, 95% CI = 0.50 to 0.90; P =.008). Recurrence-free survival at 5 years was also better in the adjuvant chemotherapy arm than it was in the observation arm (76% versus 65%, difference = 11% [95% CI = 5% to 16%]; HR = 0.64, 95% CI = 0.50 to 0.82; P =.001). Subgroup analyses provided no evidence of a difference in the size of effect of chemotherapy on survival in any pretreatment subcategory. CONCLUSIONS: Platinum-based adjuvant chemotherapy improved overall survival and recurrence-free survival at 5 years in this combined group of patients with early-stage ovarian cancer defined by the inclusion criteria of the ICON1 and ACTION trials.

Aged↗
PubMed2003

Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial.

BACKGROUND: All randomized trials of adjuvant chemotherapy for early-stage ovarian cancer have lacked the statistical power to show a difference in the effect on survival between adjuvant chemotherapy and no adjuvant chemotherapy. They have also not taken into account the adequacy of surgical staging. We performed a prospective unblinded, randomized phase III trial to test the efficacy of adjuvant chemotherapy in patients with early-stage ovarian cancer, with emphasis on the extent of surgical staging. METHODS: Between November 1990 and January 2000, 448 patients from 40 centers in nine European countries were randomly assigned to either adjuvant platinum-based chemotherapy (n = 224) or observation (n = 224) following surgery. Endpoints were overall survival and recurrence-free survival, and the analysis was on an intention-to-treat basis. The Kaplan-Meier method was used to perform time-to-event analysis, and the log-rank test was used to compare differences between treatment arms. Statistical tests were two-sided. RESULTS: After a median follow-up of 5.5 years, the difference in overall survival between the two trial arms was not statistically significant (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.44 to 1.08; P =.10). Recurrence-free survival, however, was statistically significantly improved in the adjuvant chemotherapy arm (HR = 0.63, 95% CI = 0.43 to 0.92; P =.02). Approximately one-third of patients (n = 151) had been optimally staged and two-thirds (n = 297) had not. Among patients in the observation arm, optimal staging was associated with a statistically significant improvement in overall and recurrence-free survival (HR = 2.31 [95% CI = 1.08 to 4.96]; P =.03 and HR = 1.82 [95% CI = 1.02 to 3.24] P =.04, respectively). No such association was observed in the chemotherapy arm. In the non-optimally staged patients, adjuvant chemotherapy was associated with statistically significant improvements in overall and recurrence-free survival (HR = 1.75 [95% CI = 1.04 to 2.95]; P =.03 and HR = 1.78 [95% CI = 1.15 to 2.77]; P =.009, respectively). In the optimally staged patients, no benefit of adjuvant chemotherapy was seen. CONCLUSION: Adjuvant chemotherapy was associated with statistically significantly improved recurrence-free survival in patients with early-stage ovarian cancer. The benefit of adjuvant chemotherapy appeared to be limited to patients with non-optimal staging, i.e., patients with more risk of unappreciated residual disease.

Adult↗
PubMed2002

Phase I studies with bendamustine: an update.

Bendamustine is a novel agent with both alkylating and purine-like moieties that is currently in phase II/III trials for the treatment of hematologic malignancies and breast, lung, and gastrointestinal tumors. Bendamustine was developed in the early 1960s and first used clinically in 1969 in patients with multiple myeloma. Since then, various dose and treatment schedules have been used empirically. Although bendamustine has been in clinical use for over three decades, the early clinical trials do not conform to present-day standards of good clinical practice. Therefore, it was necessary to conduct a full range of clinical trials before application for a European marketing license could be made. To date, bendamustine has been investigated both as a single agent and in combination with other anticancer drugs, in phase I, II, and III clinical trials. This article presents an overview of the recent phase I trials and a summary of ongoing clinical trials.

Antineoplastic Agents↗
PubMed2002

Clinical pharmacology of the novel marine-derived anticancer agent Ecteinascidin 743 administered as a 1- and 3-h infusion in a phase I study.

Ecteinascidin 743 (ET-743) is an anticancer agent derived from the Caribbean tunicate Ecteinascidia turbinata. In the present article, the pharmacokinetics and pharmacodynamics of ET-743 are described within a phase I study. Forty patients with solid tumors initially received ET-743 as a 1-h i.v. infusion every 21 days at nine dose levels (50-1100 microg/m(2)). The maximal tolerated dose (MTD) was 1100 microg/m(2), with thrombocytopenia and fatigue as dose-limiting toxicities (DLTs). As this MTD was substantially lower than in parallel phase I studies, dose escalation continued using a prolonged, 3-h infusion. Thirty-two patients were entered at five dose levels (1000-1800 microg/m(2)). The MTD was 1800 microg/m(2) with pancytopenia and fatigue as DLTs. The recommended phase II dose was 1650 microg/m(2) given over 3 h at which 12 patients were treated. Pharmacokinetic monitoring was performed for both treatment schedules. Non-compartmental pharmacokinetic parameters at the recommended dose with the 3-h infusion were (mean value+/-SD): clearance 87+/-30 l/h and mean elimination half-life 26+/-7 h. Pharmacokinetics were linear at the dose range tested with this schedule. The percentage decrease in platelets, white blood cells and neutrophils correlated with the area under the plasma concentration versus time curve (AUC), dose and maximal plasma concentration (C(max)). Hepatic toxicity increased with dose, AUC and C(max). Administration of 1650 microg/m(2) ET-743 over 3 h seemed clinically feasible; pharmacokinetics were linear with this schedule. Hepatic and hematological toxicities correlated with exposure to ET-743.

Adult↗
PubMed2000

Preface.

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Journal Article↗