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Volume 41, Issue 18, Pages 2861-2867 (December 2005)


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Combined radiotherapy, 5-fluorouracil continuous infusion and weekly oxaliplatin in advanced rectal cancer: A phase I study

Groupe Digestif de la Fédération Nationale des Centres de Lutte Contre le CancerEric FrançoisaCorresponding Author Informationemail address, Marc Ychoubemail address, Michel Ducreuxcemail address, Frédérique Bertheault-Cvitkovicdemail address, Marc Giovanninieemail address, Thierry Conroyfemail address, Claire Lemanskibemail address, Olivier Thomasa, Valérie Magnineemail address

Received 22 June 2005; received in revised form 17 August 2005; accepted 18 August 2005.

Abstract 

The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered concomitantly with fractionated radiotherapy in patients presenting advanced rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n=24), metastatic (n=17) and 2 with local recurrence), were included. The radiotherapy dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The initial weekly oxaliplatin dosage was 30mg/m2 and the 5FU dosage 150mg/m2/d. The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At dose level 8 (oxaliplatin 80mg/m2, 5FU 225mg/m2/d), 2 patients out of 4 presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal shock, rectovesical fistula). At dose level 7, 2 further patients presented with grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The hematological and neurological toxicities were not severe and were not dose-limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with pathological complete response and 4 (13.3%) only presented with microscopic residual disease. The results from this study enabled determination of the recommended weekly oxaliplatin dose (60mg/m2) combined with 5FU continuous infusion (225mg/m2) and fractionated radiotherapy (45 Gy) in the pre-operative treatment of advanced rectal cancer. The good safety profile of the regimen, associated with promising results in terms of histological response, suggest that the regimen could be developed in future phase II/III studies.

a Department of Medical Oncology, Gastroenterology Unit, Centre Antoine-Lacassagne, Avenue de Valombrose, 06189 Nice, Cedex 2, France

b Centre Val d’Aurelle, Montpellier, France

c Centre Gustave-Roussy, Villejuif, France

d Centre René Huguenin, St. Cloud, France

e Centre Paoli-Calmettes, Marseille, France

f Centre Alexis Vautrin, Vandoeuvre-lès-Nancy, France

Corresponding Author InformationCorresponding author. Tel.: +33 492 03 11 14; fax: +33 492 03 15 46.

PII: S0959-8049(05)00839-7

doi:10.1016/j.ejca.2005.08.029


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