Cardiac assessment of early breast cancer patients 18 years after treatment with cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy.

Background: Epirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect.

Methods: We re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin-cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m(2)) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m(2))].

Extended benefit from sequential administration of docetaxel after standard fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast cancer: the 8-year follow-up results of the UNICANCER-PACS01 trial.

Purpose: The initial report from the Programme Action Concertée Sein (PACS) PACS01 trial demonstrated a benefit at 5 years for disease-free survival (DFS) and overall survival (OS) rates with the sequential administration of docetaxel after FEC100 (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)) for patients with node-positive, operable breast cancer. We evaluate here the impact of this regimen at 8 years.

Patients And Methods: Between June 1997 and March 2000, a total of 1,999 patients (age <65) with localized, resectable, non-pretreated, unilateral breast cancer were randomly assigned to receive either standard FEC100 for 6 cycles or 3 cycles of FEC100 followed by 3 cycles of 100 mg/m(2) docetaxel (FEC-D), both given every 21 days.

Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study.

Purpose: The 4-year results of this trial demonstrated that a higher dose of epirubicin with cyclophosphamide (HEC) is superior to a lower dose of epirubicin, 60 mg/m(2) (EC), for event-free survival (EFS; 27% reduction), but is not superior to classical oral cyclophosphamide, methotrexate, and fluorouracil (CMF) in the adjuvant treatment of node-positive breast cancer. Herein we report the 15-year data on efficacy and long-term toxicity of this three-arm Belgian multicenter trial.

Patients And Methods: Between March 1988 and December 1996, 777 eligible patients were randomly assigned to six cycles of CMF, eight cycles of EC, or eight cycles HEC.

Sequential administration of epirubicin and paclitaxel for advanced breast cancer. A phase I randomised trial.

Forty-six previously untreated patients with advanced breast cancer were eligible for the present randomised phase I study. It aimed to evaluate the toxicity and activity of a therapeutic sequence with epirubicin on day 1 followed by paclitaxel on day 2 (sequence A) or the reverse sequence, ie., paclitaxel on day 1 followed by epirubicin on day 2 (sequence B).

High-dose oral medroxyprogesterone acetate or tamoxifen as adjuvant hormone therapy for node-negative early-stage breast cancer: randomized trial with 7-year update.

A randomized adjuvant trial compared tamoxifen 20 mg daily for 5 years with high-dose oral medroxyprogesterone acetate (MPA) 1 g orally for 9 months. One hundred ninety-four patients with histologically proven primary node-negative breast carcinoma were enrolled between December 1990 and October 1996, with 98 patients randomized into the tamoxifen arm and 96 into the MPA arm. At a median follow-up of 86 months, 25 relapses and 13 deaths were recorded.

Role of 2'-2' difluorodeoxycytidine (gemcitabine)-induced cell cycle dysregulation in radio-enhancement of human head and neck squamous cell carcinomas.

Background And Purpose: To try to get a better insight on the interaction between dFdC and ionizing radiation at the cellular level, we examined in vitro the effect of dFdC on the cell cycle of two human head and neck squamous cell carcinoma cell lines (SQD9 and SCC61).

Patients And Methods: Experimental conditions yielding radio-enhancement were used. Confluent cells were incubated with dFdC (5 microM) for different incubation times, washed, pulse-labeled with BrdUrd (10 microM), fixed and then processed for flow cytometry analysis.

Gemcitabine combined with cisplatin as first-line treatment in patients with epithelial ovarian cancer: a phase II study.

Objective: This phase II study was performed to evaluate the activity and toxicity of gemcitabine plus cisplatin as first-line treatment of advanced epithelial ovarian cancer.

Methods: Chemonaive patients with histologically or cytologically confirmed FIGO stage III or IV epithelial ovarian carcinoma were enrolled. Patients received cisplatin 75 mg/m(2) on Day 1 and gemcitabine 1250 mg/m(2) on Days 1 (after cisplatin) and 8 of a 21-day cycle.

A phase I study of fludarabine combined with radiotherapy in patients with intermediate to locally advanced head and neck squamous cell carcinoma.

Background And Purpose: Fludarabine, 9-beta-D-arabinofuranosyl-2-fluoroadenine, is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. In this framework, we designed two phase I trials (one conducted at M.D.

The feasibility of classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for pre- and post-menopausal node-positive breast cancer patients in a Belgian multicentric trial: a study of consistency in relative dose intensity (RDI) and cumulative doses across institutions.

Background: Classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF) including oral cyclophosphamide is still considered an important adjuvant chemotherapy regimen in patients with early breast cancer (BC). Concern has been raised regarding the feasibility of this regimen, especially in postmenopausal patients.

Patients And Methods: 254 pre- and post-menopausal node-positive BC patients aged < or = 70 years received six cycles of CMF in the context of a Belgian multicentric phase III trial of adjuvant chemotherapy.

[Benign diseases in radiotherapy: a practice survey in Belgium. Peer review of radiotherapy in Belgium].

In 1996 and 2000, a survey of radiation practice in Belgium was performed by sending a questionnaire to the different centers asking their opinion and number of patients treated. There was a great similarity between the two surveys both for indications and total number of patients irradiated. For the most common indications (prevention of cheloids, heterotopic bone formation, hyperthyroidy ophthalmopathy), there was a trend to use similar radiation technique following recent publications.

HER-2 and topo-isomerase IIalpha as predictive markers in a population of node-positive breast cancer patients randomly treated with adjuvant CMF or epirubicin plus cyclophosphamide.

Background: The predictive role of HER-2 in node-positive breast cancer patients receiving CMF or an anthracycline-based adjuvant therapy remains unclear. In addition, topo-isomerase II alpha (topo IIalpha), as the cellular target of anthracyclines, might have value as a predictive marker.

Patients And Methods: Four hundred eighty-one archival primary tumor samples were collected among 777 patients entered into a multicenter phase III trial comparing classical CMF with epirubicin cyclophosphamide (HEC) as adjuvant therapy of node-positive breast cancer.

Phase II study of vinorelbine in patients with androgen-independent prostate cancer.

Purpose: To evaluate the efficacy and toxicity of vinorelbine in a phase II study in patients with progressive metastatic androgen-independent prostate cancer.

Patients And Methods: Forty-seven men with progressive metastatic prostate cancer refractory to first-line or second-line hormonal therapy were treated with vinorelbine, a semisynthetic vinca-alkaloid. Vinorelbine was given, on an outpatient schedule, at 25 mg/m2 weekly for at least eight weeks or until progression or excessive toxicity.

Adjuvant high-dose medroxyprogesterone acetate for early breast cancer: 13 years update in a multicentre randomized trial.

The authors updated their report on a randomized trial initiated in 1982 comparing, in early breast cancer, high-dose IM Medroxyprogesterone acetate (HD-MPA) adjuvant hormonotherapy during 6 months with no hormonotherapy; node-positive patients also received 6 courses of IV CMF (day 1, day 8; q.4 weeks). 246 node-negative (NN) and 270 node-positive (NP) patients had been followed for a median duration of 13 years.

Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer.

Purpose: To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen (EC) in the adjuvant therapy of node-positive breast cancer.

Patients And Methods: Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m(2), cyclophosphamide 500 mg/m(2); day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m(2), cyclophosphamide 830 mg/m(2); day 1 every 3 weeks).

Results: Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively.

PSA kinetics after external beam radiotherapy alone or combined with an iridium brachytherapy boost to deliver 85 grays to prostatic adenocarcinoma.

Purpose: Increasing the dose to prostatic adenocarcinoma in conformal external beam therapy (EBT) has resulted in increased levels of PSA normalization and increased percentage of biochemical disease-free survival rates. However technical problems due to prostate motion inside the pelvis or patients' set-up make difficult the realization of the EBT boost fields above 72 Gy. Brachytherapy which overcomes these problems was investigated to deliver the boost dose to achieve 85 Gy.

Importance of 5-fluorouracil dose-intensity in a double randomised trial on adjuvant portal and systemic chemotherapy for Dukes B2 and C colorectal cancer.

366 patients fully resected from a Dukes B2 or C colorectal cancer were randomised to receive 6 courses of systemic chemotherapy comprising either 5-fluorouracil (5 FU) alone (arm A: 450 mg/m2/day-5/21 days) or combined folinic acid (FOL) and 5 FU (arm B: respectively 200 mg/m2 racemic form or 100 mg/m2-l-form and 370 mg/m2/day-5/21 days). 173 patients had also been initially randomised to receive one course of intraportal chemotherapy just after surgery or no portal treatment. Oral levamisole (150 mg/day; 3 days every other week) was given to all patients for one year.

Adjuvant intraportal chemotherapy for Dukes B2 and C colorectal cancer also receiving systemic treatment: results of a multicenter randomized trial. Groupe Régional d'Etude du Cancer Colo-Rectal (Belgium).

In a randomized trial, the authors evaluated the possible adjuvant activity of intraportal chemotherapy (with 5-fluorouracil 500 mg/m2/day in continuous infusion for 7 days and mitomycin C 10 mg/m2 at day 7) administered after surgery to half of the patients who underwent a full resection for Dukes B2 or C colorectal cancer. The procedure appeared manageable and safe. Two hundred and sixty patients were initially randomized, among whom 173 were finally considered as fully evaluable after having completed six courses of systemic chemotherapy.

Feasibility study combining low dose rate (192)Ir brachytherapy and external beam radiotherapy aiming at delivering 80-85 Gy to prostatic adenocarcinoma.

Background: Increasing the radiation dose to prostatic adenocarcinoma has provided higher local control rates. A total of 80 Gy seem necessary to achieve this goal but patient set-up and prostate motion remain difficult problems to solve in conformal radiotherapy. Brachytherapy which overcomes these points could be an alternative way to external beam boost fields.

Radiotherapy of pelvic malignancies: impact of two types of rigid immobilisation devices on localisation errors.

Background And Purpose: To determine the distribution of set-up errors for patients treated with and without two rigid partial immobilisation devices for pelvic malignancies.

Materials And Methods: 30 patients receiving pelvic irradiation with a four field technique underwent a total of 524 portal films. The patients are divided into 3 cohorts of 10 patients.

Effect of gemcitabine on the tolerance of the lung to single-dose irradiation in C3H mice.

In an early phase II trial combining gemcitabine (dFdC) and radiotherapy for lung carcinomas, severe pulmonary toxicity was observed. In this framework, the objective of this study was to investigate the effect of dFdC on the tolerance of the lungs of C3H mice to single-dose irradiation. The thoraxes of C3H mice were irradiated with a graded single dose of 8 MV photons; dFdC (150 mg/kg) or saline (control animals) was administered i.

The effect of 2'-2' difluorodeoxycytidine (dFdC, gemcitabine) on radiation-induced cell lethality in two human head and neck squamous carcinoma cell lines differing in intrinsic radiosensitivity.

Purpose: The present study investigated in vitro radio-enhancement by gemcitabine (dFdC) in two head and neck squamous cell carcinomas with different intrinsic cellular radiosensitivity.

Materials And Methods: Radiosensitive (SCC61, SF2=0.16) and radioresistant (SQD9, SF2=0.

Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1.

Thirty-nine tumor-bearing patients with metastatic melanoma were treated with 3 subcutaneous injections of the MAGE-3.A1 peptide at monthly intervals. No significant toxicity was observed.

Radiosensitization of mouse sarcoma cells by fludarabine (F-ara-A) or gemcitabine (dFdC), two nucleoside analogues, is not mediated by an increased induction or a repair inhibition of DNA double-strand breaks as measured by pulsed-field gel electrophoresis.

Purpose: To investigate the effect of fludarabine (F-ara-A) and gemcitabine (dFdC), two radiosensitizing nucleoside analogues, on the induction and repair of DNA dsb after ionizing radiation.

Materials And Methods: Radiosensitization of mouse sarcoma SA-NH and FSA cells was studied using a clonogenic assay. Cell survival curves were fitted with the linear-quadratic model.

[Autonomous thyroid adenoma. Value of thallium scintigraphy and pathology].

Clinical, biological, scintigraphic (99mTc, 123I, 201Tl) and histological data were reviewed in 90 patients operated for autonomous adenomas (hot nodules). Analysis of the data gave the following results: 74.4% of the nodules were solitary and 25.