Oxaliplatin, Capecitabine and Endostar as First Line Treatment for Patients With Advanced Colorectal Cancer

Inclusion Criteria:

* Histologically or cytologically confirmed metastatic or recurrent colorectal tumors with no previous treatment for advanced disease.
* Age greater than or equal to 18 years.
* SWOG performance status 0-1.
* At least one measurable lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Minimum indicator lesion size: \> 10 mm measured by spiral CT or \>20mm measured by conventional techniques.
* Have a negative serum pregnancy test within 7 days prior to initiation of chemotherapy (female patients of childbearing potential).
* Availability of tumor biopsy (paraffin embedded or fresh frozen) at the time of diagnosis and/or prior to study entry is required.
* Patients must agree to have a 20 cc blood sample drawn in addition to routine labs with each cycle of chemotherapy.

Exclusion Criteria:

* Pregnant or lactating woman.
* Life expectancy \< 3 months.
* Serious, uncontrolled, concurrent infection(s) or illness(es)
* Any prior oxaliplatin treatment, with the exception of adjuvant therapy given \> 12 months prior to the beginning of study therapy
* Prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to 5-fluorouracil, or known DPD deficiency
* Prior unanticipated severe reaction or hypersensitivity to platinum based compounds.
* Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.
* Current, recent (within 4 weeks of first infusion on this study) or planned participation in an investigational drug study.
* Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) within the last 6 months.
* History of clinically significant interstitial lung disease and/or pulmonary fibrosis.
* History of persistent neurosensory disorder including but not limited to peripheral neuropathy.
* Presence of central nervous system or brain mets.
* Major surgery, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study.
* Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
* Any of the following laboratory values:

  * Abnormal hematologic values (neutrophils \< 1.5 x 109/L, platelet count \< 100 x 109/L)
  * Urine protein: creatinine ratio \>/= 1.0 Impaired renal function with estimated creatinine clearance \< 30 ml/min as calculated with Cockroft et Gault equation:
  * Serum bilirubin \> 1.5 x upper normal limit. ALT, AST \> 2.5 x upper normal limit (or \> 5 x upper normal limit in the case of liver metastases)
  * Alkaline phosphatase \> 2.5 x upper normal limit (or \> 5 x upper normal limit in the case of liver metastases or \> 10 x upper normal limit in the case of bone disease)
* Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0
* Blood pressure \> 150/100 mmHg
* Unstable angina
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of myocardial infarction or stroke within 6 months
* Clinically significant peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0.
* Serious, non-healing wound, ulcer or bone fracture
* Carcinoma of any histology in close proximity to a major vessel, cavitation or history of hemoptysis.
* Completion of previous adjuvant chemotherapy regimen \< four weeks prior to the start of study treatment (within six weeks of study treatment for mitomycin C and nitroureas), or with related toxicities unresolved prior to the start of study treatment.
* Karnofsky performance status \<60.