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Adjuvant treatment in colorectal cancer: An update

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Abstract

Analysis of current and recently completed trials of adjuvant therapy for colorectal cancer permit a few very broad generalizations. Survival of patients initially treated by resection has improved during the past 2 decades, unrelated to adjuvant therapy. While pilot, uncontrolled, and historically controlled studies often suggest a treatment benefit, controlled trials have, to date, failed to show any advantage for adjuvant therapy in colon cancer. For rectal cancer, only those trials including radiation therapy alone or in combination with chemotherapy have provided enhanced patient survival. Superiority of preoperative versus postoperative radiotherapy has not been demonstrated.

Of interest is the current United States intergroup trial in colon cancer which is evaluating levamisole in combination with 5-fluorouracil, based on preliminary experience in a smaller study of the North Central Cancer Treatment Group which suggests that levamisole and 5-fluorouracil may be a potentially beneficial adjuvant combination. Recent reports of pharmacologic modulation of 5-fluorouracil resulting in significantly enhanced response rates in advanced metastatic colorectal cancer invite a trial of this pharmacologic concept for surgical adjuvant therapy.

Résumé

L'analyse récente ou en cours d'essais de thérapeutiques complémentaires du cancer colo-rectal a permis d'en tirer certaines leçons. La survie des opérés traités par résection s'est améliorée au cours des dernières décennies indépendamment des traitements complémentaires. Alors que des études anciennes contrôlées ou incontrôlées ont suggéré que ces traitements pouvaient être bénéfiques, des essais récents ont fait la preuve qu'ils n'entrainaient aucune amélioration du pronostic du cancer du colon. En ce qui concerne le cancer du rectum, seuls les essais associant la radiothérapie isolée ou combinée à la chimiothérapie ont démontré une amélioration relative de la durée de la survie sans que la supériorité de la radiothérapie pré-opératoire par rapport à la radiothérapie post-opératoire ait été démontrée.

En revanche, l'essai intergroupe conduit aux Etats-Unis utilisant l'association levamisole-5-FU, essai reposant sur une expérience préliminaire menée par le Groupe Nord-Central du Traitement du Cancer, suggère que ces deux agents médicamenteux peuvent constituer un traitement complémentaire à potentiel bénéfique. Des rapports récents faisant état de modulations pharmacologiques du 5-FU qui entrainent une amélioration des taux de réponse en cas de cancer colo-rectal avancé et compliqué de métastases, invitent à poursuivre cet essai de thérapeutique complémentaire.

Resumen

El análisis de los ensayos clínicos actuales y de aquellos recientemente concluidos sobre terapia adyuvante en cáncer colorrectal permite plantear algunas generalizaciones. La supervivencia de los pacientes tratados inicialmente mediante resección ha mejorado en el curso de las últimas 2 décadas, sin que esto tenga relación con la quimioterapia adyuvante. A pesar de que estudios piloto, no controlados o históricamente controlados, con frecuencia sugieren un beneficio terapéutico, los ensayos clínicos controlados, hasta la fecha, no demuestran ventaja alguna del uso de la terapia en cáncer de colon. En cáncer rectal, sólo aquellos ensayos que incluyen radioterapia, sola o en combinación con quimioterapia, han mostrado incremento en las tasas de supervivencia. La superioridad de la radioterapia preoperatoria versus la postoperatoria no ha sido comprobada.

Es de interés el estudio interinstitucional que actualmente se desarrolla en los Estados Unidos para valorar el uso de levamisol en combinación con 5-fluoruracilo, fundamentado en la experiencia preliminar con un estudio de menor envergadura realizado por el North Central Cancer Group, el cual sugiere que el levamisol y el 5-fluoruracilo pueden significar una combinación adyuvante potencialmente beneficiosa. Informes recientes sobre la modulación farmacológica del 5-fluoruracilo que resulta en un significativo incremento de las tasas de respuesta en cáncer colorrectal metastático avanzado invitan a la realización de un ensayo clínico sobre la aplicación de este concepto farmacológico en la terapia adyuvante de la cirugía.

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Authors and Affiliations

  1. Department of Surgical Oncology, Roswell Park Memorial Institute, Buffalo, New York, USA

    Harold O. Douglass Jr. M.D.

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  1. Harold O. Douglass Jr. M.D.
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Supported by PHS grant number CA 34184-04, awarded by the National Cancer Institute, DHHS.

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Douglass, H.O. Adjuvant treatment in colorectal cancer: An update. World J. Surg. 11, 478–492 (1987). https://doi.org/10.1007/BF01655813

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