bevacizumab plus capecitabin vs s-1 as maintenance treatment following first-line chemotherapy in the patients with advanced colorectal adenocarcinoma

Conditions: Colorectal Adenocarcinoma

Summary: bevacizumab plus capecitabin is a standard maintenance treatment following first-line chemotherapy in the patients with advanced colorectal adenocarcinoma. however, hand-foot syndrome induced by capecitabin will bother the patient to decrease the quality of life. s-1, an alternative of fluoropyrimidine, was proved non-inferior efficacy with lower hand-foot syndrome as first-line chemotherapy in advanced colorectal adenocarcinoma in the studies. the investigators are going to test the efficacy and safety of bevacizumab plus s-1 as maintenance treatment compared with bevacizumab plus capecitabin in colorectal adenocarcinoma


Eligibility criteria:
criteria before the start of induction therapy: inclusion criteria: histological proof of colorectal cancer (in case of a single metastasis, histological or cytological proof of this lesion should be obtained); distant metastases (patients with only local recurrence are not eligible); unidimensionally measurable disease (\> 1 cm on spiral ct scan or \> 2 cm on chest x-ray; liver ultrasound is not allowed). serum cea may not be used as a parameter for disease evaluation; in case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field. ongoing or planned first line treatment with 6 cycles of xeloda, eloxatin, and avastin. exclusion criteria prior adjuvant treatment for stage ii/iii colorectal cancer ending within 6 months before the start of induction treatment any prior adjuvant treatment after resection of distant metastases previous systemic treatment for advanced disease at randomisation: inclusion criteria: who performance status 0-1 (karnofsky ps \> 70%); disease evaluation with proven sd, pr or cr according to recist after 6 cycles of mtd chemotherapy performed in week 3-4 of the 6th cycle induction therapy, and randomisation performed in week 3-5 of the 6th cycle (see time table); laboratory values obtained ≤ 2 weeks prior to randomisation: adequate bone marrow function (hb \> 6.0 mmol/l, absolute neutrophil count \> 1.5 x 109/l, platelets \> 100 x 109/l), renal function (serum creatinine ≤ 1.5x uln and creatinine clearance, cockroft formula, \> 30 ml/min), liver function (serum bilirubin ≤ 2 x uln, serum transaminases ≤ 3 x uln without presence of liver metastases or ≤ 5x uln with presence of liver metastases); life expectancy \> 12 weeks; age \>= 18 yrs; negative pregnancy test in women with childbearing potential; expected adequacy of follow-up; institutional review board approval; written informed consent exclusion criteria history or clinical signs/symptoms of cns metastases; history of a second malignancy ≤ 5 years with the exception of adequately treated carcinoma of cervix or basal/squamous cell carcinoma of skin; previous intolerance of xelodar, eloxatinr, and/or avastinr for which any of these drugs have been permanently discontinued; patients with previous dose reductions or delays are eligible; patients with grade 2 neurotoxicity after the 6th cycle are eligible, and retreatment with eloxatinr after pfs1 should depend on the grade of neurotoxicity at that moment; known dihydropyrimidine dehydrogenase (dpd) deficiency; (planned) radical resection of all metastatic disease; uncontrolled hypertension, i.e. consistently \> 150/100 mmhg; use of more than 3 antihypertensive drugs; significant cardiovascular disease \ ctc grade 2), malabsorption syndrome, bowel obstruction, or inability to swallow tablets); concomitant treatments: concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy; full-dose anticoagulation (is allowed if started during induction therapy); continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).

Keywords: bevacizumab s-1 capecitabin maintenance