Capecitabine Versus Bolus 5-Fu Associated to Radiotherapy as Neoadjuvant Treatment for Rectal Cancer.

Study Overview
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Brief Summary
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A randomized two-arm study comparing preoperative CRT using oral capecitabine versus bolus 5-FU/LV concomitant to external beam radiation (50.5 Gy/28 fractions) for locally advanced rectal cancer. Main outcome was clinical response assessed using MRI and endorectal US 6-8 weeks after CRT. Secondary endpoints were pathological response, adverse effects, sphyncter preservation, quality of life, OS and DFS.

Detailed Description
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Patients harbouring rectal adenocarcinoma T3-4 or N>0 M0 within 10 cm to anal verge were randomized in two treatment arms: (1) capecitabina orally 825mg/m2 bid. 5 days a week for 5 weeks and (2) bolus intravenous 5-FU/LV 350mg/m2/20 mg/m2 D1-D5 on the first and fifth weeks, both combined to pelvic radiotherapy, total dose 50.4 Gy in 28 fractions. Clinical stage before and after CRT was determined using pelvic Magnetic Resonance Imaging (MRI), endorectal ultrasonography (ERUS) and chest, abdominal and pelvic Computer Tomography. Surgery was planned 6 to 8 weeks after CRT. Sphincter preservation was always considered when negative margins were possible. Pathological assessment included stage (TNM 7th Ed.) and Mandard's Tumor Regression Grade (TRG). QOL questionnaires QLQ-C30 and CR38 were completed by patients before and after CRT, after surgery and during follow-up.

Official Title
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Estudo Randomizado de Fase II Com Capecitabina Versus 5-Fluorouracil/Leucovorin em Bolus Associados à Radioterapia no Tratamento Neoadjuvante de câncer de Reto Localmente avançado: INCAGI004.

Conditions
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Rectal Neoplasm Malignant

Intervention / Treatment
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* Drug: Capecitabine Oral Product
* Drug: 5Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically proven locally advanced rectal cancer (cT3-4 or positive regional lymph node) on endorectal ultrasonography (EUS) or pelvic Magnetic Resonance Imaging (MRI) were qualified for this study. Distance from anal verge (AV) should not exceed 10 cm measured with rigid proctoscopy. Thorax and abdominal computer tomography (CT) exams were taken to rule out distant metastasis. Performance Status ECOG 0-1. Exclusion Criteria: Previous treatment for rectal cancer (RT, chemotherapy or surgical resection). Previous diagnosis of other cancers except nonmelanoma skin cancer. Uncontrolled comorbities including heart failure and miocardial infarction in the previous 6 months. Hepatic insufficiency and renal failure. Pregnancy. Serious neurologic or psyquiatric disturbances that could affect comprehension of informed consent. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomization
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capecitabine<br>Neoadjuvant capecitabine plus RT | Drug: Capecitabine Oral Product<br>* Neoadjuvant Capecitabine concomitant to external beam radiotherapy<br>* Other names: Xeloda;|
| Active Comparator: 5-Flourouracil<br>Neoadjuvant 5-Fluorouracil plus RT | Drug: 5Fluorouracil<br>* Neoadjuvant bolus 5-Fluorouracil concomitante to external beam radiotherapy<br>* Other names: 5-Fu;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical downstaging | Clinical downstaging after neoadjuvant treatment | 6-8 weeks after CRT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological downstaging | Patholgical downstaging after neoadjuvant treatment | 8 weeks after CRT |