___________________________________________________________________________ Colorectal Cancer
Resection of all lesions, including those with radiographic complete response, is recommended when technically feasible and an adequate functional liver remnant can remain. When a lesion with radiographic complete response is present in an unresectable portion of the liver, surgery may still be an option if all other visible disease can be resected. Adjuvant chemotherapy should also be considered. Closely follow the lesion to allow localized treatment or further resection for in-situ recurrence [317]. Perioperative Chemotherapy Cancer Care Ontario recommends perioperative chemotherapy for patients with resectable liver metastases and extra-hepatic metastases amenable to resection with clear margins [317]. However, the role of adjuvant chemotherapy in potentially curative liver metastases resection is uncertain [201]. Before FOLFOX and FOLFIRI were introduced, two trials randomized patients after resection of liver metastases to 5-FU/leucovorin or observation. Both studies closed early due to poor accrual, but some data were obtained. Patients randomized to 5-FU/ leucovorin or observation had five-year disease-free survival of 33.5% vs. 26.7% and overall survival of 51.1% vs. 41.1% [322]. In patients randomized to post-surgery 5-FU/leucovorin, the progression-free survival was 27.9 months compared with 18.8 months in the observation group [323]. Since the introduction of FOLFOX and FOLFIRI, multiagent chemotherapy has been evaluated as adjuvant therapy following resection of colorectal cancer liver metastases. In one study, patients randomized to 5-FU/leucovorin or FOLFIRI showed disease-free survival of 21.6 vs. 24.7 months; disease-free survival and overall survival were statistically comparable [324]. In another study, patients with up to four resectable liver metastases received perioperative FOLFOX (six cycles before and after surgery) or surgery alone. The progression-free survival was 42.4% vs. 36.2%. Reversible postoperative complications were more frequent after chemotherapy than surgery alone (25% vs. 16%), and there was one fatality after chemotherapy versus two fatalities after surgery [325]. Based on these findings, some physicians feel perioperative therapy is reasonable [201]. However, improved overall survival from resection plus chemotherapy has not been found. Intra-Arterial Chemotherapy after Liver Resection Hepatic intra-arterial chemotherapy with floxuridine for liver metastases has shown higher overall response rates but no consistent improvement in survival compared with systemic chemotherapy [201]. In one trial, patients receiving curative liver resection were randomized to combined hepatic intra- arterial floxuridine and dexamethasone plus systemic 5-FU/ leucovorin or to systemic 5-FU/leucovorin alone. Combined therapy improved two-year progression-free survival (57% vs. 42%) and overall survival (86% vs. 72%) but not median survival (72.2 vs. 59.3 months) [326].
A meta-analysis of randomized trials of fluoropyrimidine systemic therapy found no survival advantage. Furthermore, hepatic intra-arterial therapy is associated with increased local toxic effects, including liver function abnormalities and fatal biliary sclerosis [327]. Radiofrequency Ablation Radiofrequency ablation (RFA) has emerged as a safe technique (2% major morbidity and less than 1% mortality rate) that may provide for long-term tumor control [328]. With RFA, high-frequency alternating current is delivered through needle electrodes inserted into the hepatic tumor area. The generated heat induces localized coagulative necrosis and tissue destruction. RFA is performed under imaging guidance, and the patient receives local or general anesthesia [329]. With hepatic colorectal cancer metastases, RFA is indicated as primary treatment in patients medically unfit for surgery; when the number, location, and size of metastases contraindicate resection; for treatment of post-resection recurrence; and as resection adjunct to ablate small-volume colonies in the future remnant liver. The National Institute for Health and Clinical Excellence (NICE) concluded in 2009 that RFA safety and efficacy evidence was sufficient to support its use in patients unfit or unsuitable for hepatic resection and in patients with previous hepatic resection [329]. Other Local Ablation Cryosurgical ablation is an option for patients with tumors that cannot be resected and for patients who are not candidates for liver resection [330; 331]. Other local ablative techniques include embolization and interstitial radiation therapy [332]. Patients with limited pulmonary metastases, or with both pulmonary and hepatic metastases, may also be considered for surgical resection, with five-year survival possible in select patients [333]. TREATMENT-INDUCED TOXICITY AND COMPLICATIONS Chemotherapy-Induced Bone Marrow Suppression Neutropenia, thrombocytopenia, and anemia may develop with the chemotherapeutic agents used in colorectal cancer treatment. Management of these short-term complications is temporary drug cessation and supportive treatment until recovery of bone marrow function [171]. Oxaliplatin-Associated Hepatotoxicity Elevations in serum liver enzymes are common during treatment with oxaliplatin. Rarely, there is evidence of a hepatic veno-occlusive disease that presents with evidence of portal hypertension or persistent abnormalities in liver biochemistry [171].
87
MDFL2626
Powered by FlippingBook