Postoperative Hepatic Arterial Chemotherapy in High-risk Patients as Adjuvant Treatment After Resection of Colorectal Liver Metastases
Postoperative Hepatic Arterial Chemotherapy in High-risk Patients as Adjuvant Treatment After Resection of Colorectal Liver Metastases
Currently, no adjuvant study with hepatic arterial infusion in the adjuvant setting is
 opened. Recently, the results of a phase II study (NCT00268463, NSABP-C-09) assessing the
 potential benefit of systemic oxaliplatin and capecitabine alternating with HAI of FUDR,
 after resection of CRLM have been reported.

 The primary end point was 2-year survival. Fifty-five of 76 eligible patients were able to
 initiate protocol-directed therapy and completed median of six cycles (range, one to six).
 Three postoperative or treatment-related deaths were reported. Overall, 88% of evaluable
 patients were alive at 2 years. With a median followup of 4.8 years, a total of 30 patients
 have had disease recurrence, 11 involving the liver. Median disease-free survival was 32.7
 months. In conclusion alternating HAI of FUDR and systemic capecitabine and oxaliplatin met
 the prespecified end point of higher than 85% survival at 2 years and were clinically
 tolerable.
Inclusion Criteria:

 1. Histologically confirmed metastatic colorectal adenocarcinoma,

 2. Curative-intent resection (or ablation) R0 of at least 4 CRLM,

 3. Preoperative oxaliplatin- and/or irinotecan-based chemotherapy (successively or
 concomitantly) +/- non experimental biological therapy, e.g., anti-EGFR or
 antiangiogenic antibody,

 4. Confirmed radiological tumor control before surgery (i.e., objective response or
 stable disease according to RECIST1.1 criteria),

 5. WHO performance status of 0 or 1,

 6. Age ≥ 18 years,

 7. Adequate hematological function: absolute neutrophil count (ANC) > 2 x 109/L;
 platelets > 100 x 10^^9/L, hemoglobin (Hb) > 9 g/dL.

 8. Adequate liver function: serum bilirubin </= 1.5 x ULN;

 9. Aminotransferases levels </= 2.5 ULN (</= 5 ULN if liver metastases in place), and
 alkaline phosphatase level ≤ 5 ULN

 10. Creatinin clearance ≥ 30 ml/min

 11. Informed consent signed by the patient or his/her legal representative.

 12. Negative pregnancy test in women of childbearing potential within 14 days prior to
 treatment initiation (premenopausal or less than 12 months of amenorrhea
 post-menopause, and who have not undergone surgical sterilization). Both men and women
 (of childbearing potential) who are sexually active must use adequate contraception,
 during and for at least 6 months post-treatment.

 Exclusion Criteria:

 1. Extrahepatic metastatic disease (except ≤3 lung nodules (≤10 mm on chest CT scan)
 deemed amenable to curative-intent resection/ablation),

 2. Symptomatic primary tumor requiring urgent surgery, asymptomatic primary colorectal
 tumor is not a non-inclusion criteria if its

 3. Contraindication to fluoropyrimidines or oxaliplatin, as mentioned in the SMPC of
 investigational medicinal products

 4. Known dihydropyrimidine dehydrogenase (DPD) deficiency

 5. Disease progression during, or early hepatic relapse (< 6 months) after the end of,
 oxaliplatin-based adjuvant chemotherapy following primary tumor resection

 6. History of hepatic arterial infusion with any treatment (chemotherapy,
 radioembolisation),

 7. Peripheral neuropathy> grade 1,

 8. History of cancer within 5 years prior to entry into the trial other than adequately
 treated basal-cell skin cancer or in situ carcinoma of the cervix

 9. Concomitant administration of cimetidine

 10. Concomitant medications/comorbidities that may prevent the patient from receiving
 study treatments,

 11. Patient already included in another clinical trial with an experimental molecule,

 12. Pregnancy or lactation,

 13. Patients deprived of liberty or under guardianship,

 14. Patients unable to undergo medical monitoring test for geographical, social or
 psychological reasons.

 15. Patients must not have any uncontrolled concurrent illness including, but not limited
 to, severe active or uncontrolled infection, symptomatic congestive heart failure,
 unstable, angina pectoris, cardiac arrhythmia, uncontrolled diabetes mellitus or
 psychiatric illness/social situations that would limit compliance with study
 requirements resection is planned (REVERSE strategy authorized)