Many patients are first seen with advanced hepatobiliary tumors because of lack of early clinical symptoms and they usually do not have a chance for curative surgery. Debate still goes on about a standard chemotherapy regimen in patients with hepatobiliary tumors. In this report, we investigated the efficacy and toxicity of bolus 5-FU, cisplatin, and epiribucin regimen which was found useful for gastric cancers, in former studies [
11].
Commonly used chemotherapeutic agents in treatment of inoperable biliary tumors are 5- FU and mitomycin C (MMC). Adding alkylating agents to 5-FU chemotherapy had been tried in the past, but it was showed that it did not change survival and quality of life [2]. In one study, only cisplatin was administered to nine patients with biliary tumors and no benefit with cisplatin monotherapy was shown [12]. Generally, response rates with monotherapies are partial and less than 20%. Although response could be achieved with monotherapies, response times are too short and have no affect on survival. Other than monotherapies, FAM is one of the commonly used combined chemotherapy regimens. In one study where FAM (5-FU, Doxorubicin, MMC) was used every 4 weeks, the objective response rate was 31% [3]. We observed better response rates than the old FAM regimen in our study. Ellis et al. [13] used ECF (epirubicin 50 mg/m2, cisplatin 60 mg/m2, 5 FU 200 mg/m2 i.v. continuous infusion) for biliary tumors in their study. The objective response rate was 40% (8 of 25 patients) and median duration of response was 10 months (5-22 months). In despite of the administration of 5-FU as i.v. bolus in our study, our response rate was 37.5% and median duration of response was 7 months. When our study was compared with the study of Ellis et al.’s, the response rates and median duration of response were similar although our administration of 5-FU was bolus instead of continuous infusion. Di Lauro l et al. [14] used epirubicin 60 mg/m2, cisplatin 75 mg/m2, 5-FU 500 mg/m2 i.v. continuous chemotherapy to 15 patients with unresectable tumors (6 gallbladder, 5 cholangiocarcinoma and 4 biliary duct carcinoma). They observed complete response in one patient, partial response in four patients and overall response rate was found as 33% [14]. The response rate was better in our study compared to Di Lauro’s study, though administration of 5-FU was as bolus.
The role of chemotherapy and which regimen should be used for HCC still remain controversial. Doxorubicin is the most frequently used drug and thought to be the most effective agent [15,16]. Monotherapy studies were commonly done with doxorubicin and response rates were found approximately 11-15% [17]. In the other monotherapy studies, 5-FU and cisplatin also were used and response rates were found in the range of 10-11% and 8.5% [6,18]. While response rates were low in the monotherapies with 5-FU or doxorubicin, the response rates were higher in our ECF regimen (37.5%). Generally, higher response rates were found with combined chemotherapy regimens especially including 5-FU or doxorubicin but when their results are compared with untreated patients, improvement on survival cannot be shown with any combined regimen [9]. Ellis et al. [13] reported partial response in 2 of 7 patients (%29) by using the ECF chemotherapy regimen. The response rate in our study was similar to Ellis et al.’s study, despite the administration of bolus 5-FU. Boucher et al. [19] administered ECF regimen to 21 patients with HCC (locally advanced or metastatic) and found a 14.5% response rate and median survival as 10 months. The low response rate in this study could be explained as the tumor development was seen in cirrhotic liver, in most of the cases, and the patient group was not homogeneous. This regimen was extremely well tolerated by the patients. Our study didn’t have any neutropenia fever case while there were four cases in Ellis et al.’s study. Major hematological toxicity was minimal and the rate was equal to Ellis et al.’s study (Leukopenia 17%, Thrombocytopenia 17%). In our study, the most seen adverse effect was alopecia.
In conclusion, 5-FU and doxorubicin are the most commonly used and effective agents in hepatobiliary tumors. With this regimen, which is a combination of these drugs, objective response rates could be achieved but the most active combination chemotherapy regimens could not be developed yet. It seems that it is wiser to administer 5-FU continuously. It is likely that further studies with larger and homogeneous groups of patients will help to find an answer for more definite results.
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