Selecting Treatment in Colorectal Cancer: Capecitabine or 5-fluorouracil Selection According to Polymorphisms in TS-3'UTR and ERCC1-118 to be Combined With Oxaliplatin or Irinotecan as First-line Chemotherapy in Advanced Colorectal Cancer
- informed consent signed
- Histological or citological adenocarcinoma confirmation carcinoma on the colon or
colorectal metastatic or relapsed patients with adenocarcinoma of colon or recto,
confirmed histologically with metastatic disease
- measurable disease (following RECIST criteria)
- ECOG ≤ 2
- older or equal 18 years old
- life expectancy superior to 3 months
- Adequate or moderate renal function: renal function (Creatinine clearance >
30mL/min), based on Cockroff - Gault.
- Potential fertile women negative pregnancy test in serum or urine, 10 days prior the
first study dose given
- Use an adequate contraceptive method
- Patients treated previously with Bevacizumab
- Non measurable lesion as only disease evidence
- Previous chemotherapy treatment for adjuvant or neoadjuvant disease (no metastatic
(M0), or immunotherapy active/passive for the advance or metastatic disease. It is
permitted the adjuvant or neoadjuvant treatment it is has finished at least 6 months
before the initiation of the study drug.If the patient has received an adjuvant
treatment previously the patient cannot participate if disease progression has been
confirmed during the treatment or on the 6 months later
- Prior radiotherapy is allowed if it has not been administered in the target lesions
selected for this study, unless progression of said lesions in the irradiated field
is documented, and as long as treatment has concluded at least 4 weeks before
beginning the study.
- Prior surgical treatment of the disease in stage IV is allowed
- Functional dependency
- Previous serious adverse events or unexpected to fluoropyrimidine treatment and /o
patients with proved deficit in dehidropirimidin dehydrogenase (DPD)
- Patients classified as "weak or fragile"
- Cardiac concomitant present: Symptomatic auriculoventricular arrhythmia history, and
/ cardiac arrhythmias requiring medication or peripheral vascular disease, grade II
or higher. Furthermore, those patients who have had a myocardial infarction in the
year prior to beginning the treatment of the study will be excluded.
- History of another neoplastic disease during the last five years, with the exception
of cured basal cell carcinoma of the skin and cervical carcinoma in situ.
- History or indications of CNS disease in the physical examination.
- History of psychiatric disability that the investigator considers clinically
significant, which prevents the patient from granting the informed consent or
interferes with compliance of taking the oral medication.
- Uncontrolled hypertension or clinically significant (i.e. active) cardiovascular
disease: CVA/stoke (≤ 6 months prior to randomisation), myocardial infarction (≤ 6
months prior to randomisation), unstable angina, New York Heart Association (NYHA,)
Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring
- Lack of physical integrity of the upper gastrointestinal tract, malabsorption
syndrome or inability to take oral medication.
- Patients subjected to organ allograft who require immunosuppressive treatment.
- Severe, non-cicatrized osseous fractures, wounds or ulcers
- Indications of hemorrhagic diathesis or coagulopathy.
- Severe, uncontrolled intercurrent infections or other severe, uncontrolled
- Any of the following laboratory values:
1. Absolute neutrophil count (ANC) < 1.5 x 109/l
2. Platelet count < 100 x 109/l
3. Hemoglobin < 10 g/dl (it can be transfused to maintain or exceed this level)
4. International Normalized Ratio (INR) > 1.5
5. Total bilirubin > 1.5 times the upper limit of normal (ULN)
6. ALAT, ASAT > 2.5 x ULN or > 5 x (ULN) in the case of hepatic metastases
7. Alkaline phosphatase > 2.5 x ULN or > 5 x ULN in the case of hepatic
metastases or > 10 x ULN in the case of osseous metastases.
- Patients subjected to a major surgical procedure, open biopsy or who have had
significant traumatic lesions within the 28 days prior to beginning the treatment of
the study or in whom it is foreseen that a major surgical procedure will be necessary
during the course of the study; fine-needle aspiration within the 7 days prior to
beginning the treatment of the study.
- Current or recent use (within the 10 days prior to beginning the treatment of the
study) of oral or parenteral anticoagulants at complete doses or thrombolytic agents.
The use of low doses of warfarin is allowed, with an International Normalized Ratio
[INR] of < 1.5.
- Daily chronic treatment with high doses of aspirin (> 325 mg/day) or non-steroid
anti-inflammatory medications (which inhibit the platelet function at doses used for
treating chronic inflammatory diseases).
- Patients who have received any drug or agent/procedure under research, i.e., who have
participated in another clinical trial during the 4 weeks prior to beginning the
treatment with the medications of the study.
- Pregnancy or lactating woman. Woman with reproductive potential unless using an
effective method of contraception (Postmenopausal woman must have been amenorrheic
during at least 12 months).
- Known hypersensitivity to any of the study drugs or excipients of the Bevacizumab or
to Chinese hamster ovary cell products or to other recombinant human or humanised