Adjuvant Chemotherapy in Resectable Cholangiocarcinoma Patients

Kosin Wirasorn; Thundon Ngamprasertchai; Narong Khuntikeo; Ake Pakkhem; Piti Ungarereevittaya; Jarin Chindaprasirt; Aumkhae Sookprasert

Disclosures

J Gastroenterol Hepatol. 2013;28(12):1885-1891. 

In This Article

Discussion

These findings demonstrated the benefits of AC in resectable cholangiocarcinoma patients in the aspect of survival. Although the groups had some different baseline characteristics, in particular serum albumin and age, the subgroup analysis revealed significant favorable outcomes of AC in patients with serum albumin above 3 g/dL and patients with age above 50 years. The authors also found that the patients who received combined gemcitabine and capecitabine had the longest survival time among all regimens.

The proportion of R0 in the authors' institute is approximately 51% of all cholangiocarcinoma. Similarly, the previous review literatures of tumor resections revealed that the proportion of R0 greatly varies ranging between 30 and 80%.[16] The majority of patients were locally advanced stages (AJCC staging 3 and 4, 61.2% of all patients). It is difficult to approach tumor masses resulting in less successful rate of total tumor removal. Thus, the current proportion of R1 in the authors' institute is slightly higher when compared with the previous studies.[16]

There were a few studies that proved the benefits of AC in resectable cholangiocarcinoma patients. Previous research verified advantages of AC with mitomycin C and 5-FU in pancreaticobiliary carcinoma patients after surgery.[17] This study enrolled 138 cholangiocarcinoma patients from a total of 508 patients. In the subgroup analysis of cholangiocarcinoma patients, however, AC demonstrated a nonsignificant 5-year survival and 5-year disease-free survival. Benefits of the combination of intravenous gemcitabine and oral S-1 were shown in advanced biliary carcinoma patients who received aggressive surgical resection.[18,19] Recently, a systematic review and meta-analysis established beneficial effects of adjuvant therapy in the treatment of biliary tract cancer, including gall bladder and bile duct cancer.[20] Adjuvant therapy tended to be beneficial in the cholangiocarcinoma group; the overall survival was significantly improved in lymph node metastasis and surgical marginal positive subgroups. Adjuvant therapy in this research, however, included not only postsurgical single and combined agent chemotherapy, but also other treatment modalities of concurrent chemoradiotherapy and radiotherapy. The possible mechanism of AC in cholangiocarcinoma is preventing outgrowth of micrometastatic disease which consequently prolongs disease-free survival and overall survival time in cancer patients.[10,21,22]

Combined chemotherapy was demonstrated to result in a higher response rate and marginally longer survival time compared with single agent chemotherapy in advanced stage biliary tract cancer patients.[22] Gemcitabine was determined as the most active agent in treatment of biliary tract cancer.[23] Previous studies verified that combined chemotherapy that was gemcitabine-based yielded more benefits in response rate, progression-free survival, and overall survival in bile duct cancer patients than other regimens.[24–26] Previous publications reported that median overall survival in advanced unresectable biliary tract cancer patients who received combination of gemcitabine and capecitabine ranged from 12 to 14 months; however, there was no report of gemcitabine and capecitabine in resectable cholangiocarcinoma patients.[27–29]

Previous studies also reported that prognostic factors for resectable cholangiocarcinoma were preoperative CA19–9, tumor staging, lymph node metastases, tumor differentiation, and surgical margin status.[17,30–32] These high-risk features are associated with residual tumor detection of disseminated tumor cells and circulating tumor cells. The results demonstrated benefits of AC in patients who had high-risk features for recurrence; this finding was similar to results of previous studies.[19,20,33,34]

The strength of this study is that the authors enrolled a large sample size when compared with former studies. However, this study was retrospective study; consequently, some of data were not complete for analysis, and some factors, which might affect the survival time of patients, could not be controled such as ages of patients and the levels of albumin. Additionally, the duration time of follow up was not equally controled for each patient; therefore, the relapse-free survival of patients could not be presented.

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