Neoadjuvant therapy of rectal carcinoma with UFT–leucovorin plus radiotherapy

Feliú, Jaime; Calvillo, Jorge; Escribano, A.; Castro, Javier de; Sanchez, Maria E.; Mata, Alberto G.; Espinosa, Elena; Grande, A. García; Mateo, A; Barón, Manuel González

doi:10.1093/annonc/mdf116

Cited by 61 publications

(29 citation statements)

References 26 publications

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“…[24][25][26][27] A number of phase II trials have suggested that preoperative CRT followed by surgery does not adversely affect functional outcome. 28,29 The scarce available data in the 4 included phase III studies did not allow to perform a meta-analysis of QoL related parameters. However, preliminary functional outcome data of the EORTC 22921 study (published as abstract only) demonstrated a significantly worse subjective anorectal function in CRT patients compared to RT alone.…”

Section: Discussionmentioning

confidence: 99%

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis

Ceelen

Fierens

Nieuwenhove

et al. 2009

Intl Journal of Cancer

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Combining chemotherapy with preoperative radiotherapy (RT) has a sound radiobiological rationale. We performed a systematic review and meta-analysis of trials comparing preoperative RT with preoperative chemoradiation (CRT) in rectal cancer patients. The Cochrane Central Register of Controlled Trials, Web of Science, Embase and Medline (Pubmed) were searched from 1975 until June 2007. Dichotomous parameters were summarized using the odds ratio while time to event data were analyzed using the pooled hazard ratio for death. From the primary search result of 324 trials, 4 relevant randomized trials were identified. The addition of chemotherapy significantly increased grade III and IV acute toxicity (p 5 0.002) while no differences were observed in postoperative morbidity or mortality. Preoperative CRT significantly increased the rate of pathological complete response (p < 0.001) although this did not translate into a higher sphincter preservation rate (p 5 0.29). The local recurrence rate was significantly lower in the CRT group (p < 0.001). No statistically significant differences were observed in disease free survival (p 5 0.89) or overall survival (p 5 0.79). Compared to preoperative RT alone, preoperative CRT improves local control in rectal cancer but is associated with a more pronounced treatment related toxicity. The addition of chemotherapy does not benefit sphincter preservation rate or long-term survival. Future trials should address improvements in the rate of distant metastasis and overall survival by incorporating more active chemotherapy. ' UICCKey words: rectal cancer; radiotherapy; surgery The incidence of fatal cases of colorectal cancer in Europe exceeds 200,000 per year. 1 Because of the specific anatomy and biology of rectal cancer, surgery alone historically has been associated with local recurrence in up to 1 in 4 patients. 2 Locally recurrent disease is usually incurable, causes important morbidity and suffering and gives rise to systemic metastases. In the last few decades, improvements in surgical technique have dramatically lowered the incidence of locally recurrent disease. Careful pathological studies have clearly demonstrated that the major cause of local recurrence is the persistence of tumor foci within the mesorectum. 3,4 Intact removal of the entire mesorectum (total mesorectal excision or TME) in cancers of the mid or lower third of the rectum was pioneered by Heald and has resulted in local recurrence rates lower than 5-10%. [5][6][7] Parallel to improvements in surgical technique, adjuvant therapy regimens have been tested in clinical trials in an effort to reduce local recurrence rates. Neoadjuvant radiotherapy (RT) has been shown to significantly decrease local recurrence rate and improve survival provided a biologically equivalent dose (BED) of at least 30 gray (Gy) is administered. 8 The advantages of preoperative over postoperative RT include enhanced effectiveness in well-oxygenated tissue, downstaging of advanced tumors and better treatment compliance. 9 The theoretical ...

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Section: Discussionmentioning

confidence: 99%

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis

Ceelen

Fierens

Nieuwenhove

et al. 2009

Intl Journal of Cancer

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“…However, tumor downstaging was more common with preoperative UFT/LV than with 5FU/LV (59.2% versus 43.3%; p = 0.04). In the report of Feliu et al [8], 43% of patients receiving UFT 350 mg/m 2 suffered Grade 3 -4 gastrointestinal toxicity.…”

Section: Discussionmentioning

confidence: 96%

“…Phase II studies have shown that the UFT/radiotherapy combination is effective and well tolerated in the preoperative treatment of rectal cancer [7][8][9][10][11]. On the other hand, CDHP (gimeracil), a component of S-1, has potent radiosensitizing property [12].…”

Section: Introductionmentioning

confidence: 99%

A Phase II Trial of Preoperative Chemoradiotherapy with Oral DPD-Inhibitory Fluoropyrimidines in Patients with Advanced Rectal Cancer

Hotchi¹,

Okitsu²,

Miura³

et al. 2012

JCT

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Background: Preoperative chemoradiotherapy (CRT) with 5-FU has been widely used to improve local control of disease and to preserve anal sphincter in the treatment of rectal cancer. UFT and S-1 as oral dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidines enhance the therapeutic effect of 5-FU by modulating its metabolic pathways. The purpose of this study was to evaluate the efficacy and toxicity of CRT using UFT versus S-1 in patients with locally advanced rectal cancer. Methods: Fifty-nine patients who received preoperative CRT (40 Gy radiotherapy) were randomly assigned to either UFT or S-1 groups. UFT and S-1 were administered during the radiotherapy course. Response to CRT was determined using a histopathologic examination and RECIST of surgically resected specimens and classified as responders (CR, PR and Grade 2, 3) or nonresponders (SD, PD and Grade 0, 1). Results: All patients were randomly allocated to S-1 group (n = 30) or UFT group (n = 29). Pathological response rate (Grade 2 and Grade 3) was 57% in the S-1 group and 45% in the UFT group (p = 0.36). Pathological complete response (CR) rate (Grade3) was 7% in the S-1 group and 4% in the UFT group (p = 0.98). There was no statistically significant difference between the two groups in regard to the response rate of RECIST (p = 0.52). There was no statistically significant difference between the groups based on the downstaging rate, resection of tumor, sphincter preservation and marginal invasion. The incidence of Grade 3 diarrhea was significantly more frequent in the S-1 group (7%) compared with the UFT group (0%) (p = 0.02). Conclusion: The results supported the conclusion that CRT using UFT or S-1 is effective and feasible for patients with locally advanced rectal cancer.

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“…En nuestra casuística, la respuesta global al tratamiento neoadyuvante fue en torno al 47%, con una respuesta patológica completa del 11%, que está dentro de las cifras encontradas en la literatura (2,(26)(27)(28)(29)(30)(31)(32)(33), si bien hemos observado un aumento de esta cifra en comparación con los resultados obtenidos en nuestro hospital entre los años 1995-2002 (4,7%), pudiendo ser debido no sólo a la mayor experiencia, sino también a la mejora en el equipo de radioterapia e instalaciones desarrollada en los últimos años, así como a la utilización de nuevos agentes quimioterápicos. Si comparamos nuestros resultados con otros autores (26)(27)(28)(29)(30)(31)(32)(33), observamos que algunos de ellos presentan cifras de respuesta tras el tratamiento neoadyuvante mayores que las nuestras. Tenemos que comentar que eso se debe a la diferente forma de evaluar la respuesta al tratamiento neoadyuvante.…”

Section: Discussionunclassified

Abordaje multidisciplinar en el tratamiento del cáncer de recto: eficacia del tratamiento neoadyuvante

Priego

Sanjuánbenito

Morales

et al. 2008

Rev. esp. enferm. dig.

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Priego P, Sanjuanbenito A, Morales V, Lobo E, Martínez Molina E, Rodríguez Velasco G, Fresneda V RESUMENObjetivo: evaluar el papel de la terapia neoadyuvante en el tratamiento del cáncer de recto en nuestro hospital, tras la implantación de un grupo multidisciplinar de trabajo (MDT).Material y métodos: desde enero de 2000 hasta diciembre de 2005 se ha evaluado en sesión clínica por el grupo MDT un total de 90 pacientes diagnosticados de adenocarcinoma de recto e intervenidos quirúrgicamente tras recibir tratamiento neoadyuvante con radioquimioterapia (QMRT). La edad media fue de 65,04 años (21-83 años), siendo un 67% varones y un 33% mujeres. Los procedimientos quirúrgicos realizados fueron fundamentalmente resección anterior baja en un 50% y amputación abdominoperineal en un 42,2%.Resultados: la tasa de complicaciones asociada al uso del tratamiento neoadyuvante fue del 54,44%, siendo más frecuentes las gastrointestinales. Sin embargo, esta toxicidad fue bien tolerada en la mayor parte de los casos, siendo grave y acarreando la suspensión del tratamiento quimioterápico en 2 pacientes (2,2%). El análisis anatomopatológico de las piezas resecadas demostró una respuesta completa en 10 casos (11,1%) y una respuesta parcial (disminución del parámetro T de la clasificación TNM) en 32 casos (35,6%), con lo que la respuesta global del tratamiento neoadyuvante fue del 46,6%. Entre las complicaciones postoperatorias se produjeron un 8,3% de dehiscencias anastomóticas, un 34,2% de complicaciones de la herida perineal y un 12,2% de complicaciones urinarias. La mortalidad quirúrgica fue del 0%. La tasa de recidiva pélvica fue del 4,4% y la sistémica del 22,2%. La supervivencia actuarial global y libre de enfermedad a los 5 años fue del 80 y 64% respectivamente.Conclusión: el tratamiento QMRT neoadyuvante proporciona una cifras bajas de recidiva pélvica junto con buenas tasas de supervivencia, no añadiendo una morbimortalidad importante al acto quirúrgico. La evaluación sistemática por un grupo MDT en el contexto de un protocolo clínico parece ofrecer al paciente mejores oportunidades de curación.Palabras clave: Cáncer de recto. Neoadyuvancia. Radioterapia. Quimioterapia. Supervivencia. Recidiva. Respuesta patológica. Abordaje multidisciplinar. ABSTRACTObjective: the aim of this study was to assess the impact of neoadjuvant treatment on rectal cancer following involvement of a multidisciplinary team (MDT).Materials and methods: between January 2000 and December 2005, 90 patients with rectal adenocarcinoma were evaluated by a MDT and operated on after receiving neoadjuvant treatment with radiochemotherapy (RTCT) -67% were men and 33% were women, with a mean age of 65.04 years (21-83 years). Surgery was low anterior resection in 50% and abdominoperineal amputation in 42.2%.Results: the rate of complications associated with neoadjuvant treatment was 54.4%, with gastrointestinal complications being most frequent. However, this toxicity was tolerated by most patients. It was severe in two cases (2.2%), leading to chemotherapy d...

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Neoadjuvant therapy of rectal carcinoma with UFT–leucovorin plus radiotherapy

Abstract: Preoperative therapy with radiotherapy and UFT-6SLV downstaged 63% of tumors and allowed a sphincter-preserving procedure in some patients. Toxicity was moderate. This scheme is convenient because of the oral administration of chemotherapy.

Cited by 61 publications

References 26 publications

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis

A Phase II Trial of Preoperative Chemoradiotherapy with Oral DPD-Inhibitory Fluoropyrimidines in Patients with Advanced Rectal Cancer

Abordaje multidisciplinar en el tratamiento del cáncer de recto: eficacia del tratamiento neoadyuvante

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