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 Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 3  |  Issue : 2  |  Page : 153-156

Best supportive care compared with chemotherapy and radiotherapy for unresectable gallbladder cancer: A tertiary care institute experience


1 Department of Radiation Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
2 Department of Surgery, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

Date of Web Publication9-Apr-2014

Correspondence Address:
Pramod Kumar Singh
Department of Radiotherapy, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-0513.130214

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  Abstract 

Context: Gallbladder represent the most common cancer among biliary tree, complete surgery offers only chance of cure, but most of patients with unresectable or metastatic stage, in such patients only palliative treatment be given. Aims: The aim of this retrospective study is to evaluate efficacy of chemotherapy with gemcitabine and oxaliplatin (GEMOX), and or with radiotherapy over best supportive care (BSC)) in unresectable gallbladder cancer (GBC). Materials and Methods: Patients with unresectable GBC were evaluated from our center between 2008 and 2011. Three cohorts were identified. Group A, BSC, Group B chemotherapy with GEMOX two weekly for maximum of six cycles. Group C, Chemotherapy with GEMOX and Radiotherapy. Patients underwent percutaneous transhepatic biliary drainage (PTBD) or Endoscopic retrograde cholangiopancreatography (ERCP) when required. Results: Total 50 patients included in analysis. 19 are male and 31 are female. 14 patients in Group A. 18 patients in Group B and 18 in Group C. Median follow up was 8.8 month. The progression free survival (PFS) of patients who received of BSC at 15 month was 18%. PFS of patients who received chemotherapy (CCT) at 28 month was 30%. PFS of patients who received CCT Chemotherapy and radiotherapy PFS at 15 month was 38%. When compared all three group none is statically significant (P = 0.538). Conclusion: Judicious used of BSC along with chemotherapy and or with radiotherapy may help in increase in period of stable disease along with overall survival (OS) in selected group. In our retrospective analysis CCT with GEMOX and with radiotherapy has helped in improving the OS and PFS in few patients who had good performance status.

Keywords: Chemotherapy, endoscopic retrograde cholangiopancreatography, gallbladder, percutaneous transhepatic biliary drainage, radiotherapy


How to cite this article:
Singh PK, Kapoor R, Kumar R, Bahl A, Kumar N, Gupta R, Sharma SC. Best supportive care compared with chemotherapy and radiotherapy for unresectable gallbladder cancer: A tertiary care institute experience. Clin Cancer Investig J 2014;3:153-6

How to cite this URL:
Singh PK, Kapoor R, Kumar R, Bahl A, Kumar N, Gupta R, Sharma SC. Best supportive care compared with chemotherapy and radiotherapy for unresectable gallbladder cancer: A tertiary care institute experience. Clin Cancer Investig J [serial online] 2014 [cited 2019 Oct 23];3:153-6. Available from: http://www.ccij-online.org/text.asp?2014/3/2/153/130214


  Introduction Top


Gallbladder cancer (GBC) is the most common biliary tract cancer. For some unknown reason, GBC is a common type of cancer among the females in the northern part of India. Incidence varies by geographic region and racial ethnic group. Age-adjusted incidence of GBC among females in Delhi is 7.4 persons/100,000 population per year (it is the fourth most common cancer in females after breast, cervix, and ovary). [1] The reasons for high incidence in this population are not well-understood. Chile and Bolivia (10-15 persons/100,000 population/year) are other high incidence areas. [2] One of the highest incidences in India has been reported from Kamrup Urban District (10.2/100,000 female). [3] Only 10% of patients are suitable for surgery, and the rest of the patients present in advanced and unresectable stage and are candidates for palliative treatment only. Currently, there is no standard chemotherapy for GBC, and the majority of studies have included patients from all subsites of biliary tract cancers. With various chemotherapeutic agents (with or without fluorouracil (FU)) response rates were reported in 0-36% of patients. [4],[5],[6],[7],[8],[9],[10] Median survival for patients presenting with unresectable disease is 2 to 4 months, with fewer than 5% patients surviving 1 year. [11] Gemcitabine and oxaliplatin as single agents or in combination (GEMOX) with other drugs have shown activity in adenocarcinoma of pancreas, gallbladder, and biliary tracts. [6],[7],[8],[12],[13],[14],[15],[18],[19] Most of the reported studies have included patients with all subsites of biliary tract cancers. However, biliary tract cancer includes cholangiocarcinoma, GBCs, and ampullary tumors. These various tumors are likely to have a different biology and clinical course as evidenced by the fact that patients with cholangiocarcinoma have a better median survival than patients with GBC. Median survival reported for GBC in various studies is in the range of 4-11 months, studies involving mainly cholangiocarcinoma have reported median survival of 15-16 months suggesting a difference in the biology of the two diseases. Gemcitabine is among several new anticancer drugs under investigation in the treatment of biliary tract cancer. Objective responses of up to 36% have been reported in different series. [5],[7],[9],[11] Combinations of gemcitabine and cisplatin have been studied with somewhat higher response rates. Two phase II studies and one phase III study have reported using this combination. Response rates of 28-38% and median survival of 4.6-8.4 months was reported. [8],[16] A randomized trial tried to address the issue of chemotherapy in biliary tract malignancy recently. [17] Of 410 total patients, who were randomly assigned between gemcitabine with cisplatin and gemcitabine alone, only 36% had GBC as primary site. Median overall survival (OS) was 11.7 versus 8.2 months (P = 0.002). Patients with primary GBC also had a similar benefit with gemcitabine and cisplatin as seen in subgroup analysis. Oxaliplatin is a third-generation platinum compound with much less emetic and renal toxicity compared with high-dose cisplatin. Combination GEMOX may be a suitable alternative to gemcitabine and cisplatin.


  Materials and Methods Top


This was a retrospective analysis of 50 patients. Inclusion criteria included patients who had biopsy or fine needle aspiration cytology-proven unresectable or metastatic adenocarcinoma of gallbladder. Three arm study: Group A, best supportive care (BSC); Group B chemotherapy with GEMOX 2 weekly for maximum of six cycles; and Group C, CCT with GEMOX and radiotherapy. Baseline characteristics of enrolled patients are presented in [Table 1]. Patients were underwent percutaneous transhepatic biliary drainage (PTBD) or endoscopic retrograde cholangiopancreatography (ERCP) when required. In BSC patients received only symptomatic treatment. Patients receiving chemotherapy response assessed after three cycles and if favorable response than continue up to six cycle. Radiotherapy given dose of 30-45 Gy in 10-25 fractions by three-dimensional conformal radiotherapy (3DCRT). Treatment for patients with grade 3 or 4 toxicity was either delayed until resolution of toxicity or return of toxicity to lower than grade 2. Chemotherapy dose was reduced by 25% and rounded off in cases of grade 4 neutropenia or thrombocytopenia. Response Evaluation Criteria in Solid Tumors (RECIST) was used for assessment of complete response (CR), partial response (PR), stable disease, and progressive disease. Response assessment was done by repeat computed tomography (CT) scan after three cycles and six cycles in the GEMOX arm. This was done so patients had assessment after completing half of the planned chemotherapy. During follow-up, CT scan was done every 3 months and thereafter every 6 monthly. Patients who developed progressively increasing jaundice during the follow-up were considered to have progressive disease. For statistical analysis data was arranged in Statistical Package for Social Sciences (SPSS), version 19. Descriptive studies were done for parameter, survival, progression free survival and OS for the entire cohort. The log-rank test was used to analyze prognostic factors for the entire cohort. Kaplan-Meier analysis used for survival analysis. P value < 0.05 is considered as statically significant.
Table 1: Patient's characteristics

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  Results Top


Total 50 patients included in analysis, 19 are male and 31 are female. Fourteen patients in Group A, 18 in Group B, and 18 in Group C. Median follow-up was 8.8 months. The progression free survival (PFS) of patients who received of BSC at 18 month was 10%. PFS of patients who received CCT at 18 month was 28%. PFS of patients who received CCT and radiotherapy PFS at 18 month was 38% [Figure 1], [Figure 2], [Figure 3]. When compared all three group none is statically significant (P = 0.538). All three arms were well-balanced with regards to age, sex, presenting symptoms, liver metastases and prior surgical interventions in form of ERCP or PTBD. Only four patients experience grade 4 neutropenia, which was managed by granulocyte colony-stimulating factor (G-CSF) and antibiotics.
Figure 1: Kaplan-Meier estimation of survival of patients

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Figure 2: Kaplan-Meier estimation of survival of patients who received best supportive care (BSC), CCT, and CCT with radiotherapy

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Figure 3: Kaplan-Meier estimation of survival of patients who received BSC and CCT and or radiotherapy

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  Discussion Top


GBC is one of the most common biliary malignancies. Currently, there is no standard chemotherapy protocol for unresectable GBC, and median survival for patients presenting with unresectable disease is 2-4 months, with 1-year survival lower than 5%. [11] There were only two randomized trials comparing BSC and chemotherapy in biliary tract cancer (not limited to GBC only) using FU-based chemotherapy when this trial was conceived. In the study by Glimelius et al., [20] patients were randomly assigned to FU-based chemotherapy or BSC. Median OS was 6.5 months in the chemotherapy group and 2.5 months in BSC group (P = 0.1). It was possible that because of the small sample size, statistical significance could not be achieved. In another study by Takada et al., [10] chemotherapy was compared to BSC. Patient population was heterogeneous including pancreatic, GBC, and biliary tract cancers. No significant improvement was seen with use of chemotherapy. GEMOX are emerging as commonly used drugs, either as a single agent or in combination. The study by Doval et al., [8] using gemcitabine and cisplatin reported 38% response rates and 4.8 months of median survival. Andre et al., [9] reported a median PFS of 5.7 months compared with the 8.5 months reported in this study. However, in that study, GEMOX were used in doses of 1,000 and 100 mg/m 2 , respectively, every 2 weeks. In another study, median PFS of 3 months was reported. [12] Modified GEMOX (mGEMOX) was more toxic than fluorouracil and folinic acid (FUFA). The most common toxicities were vomiting, myelosuppression, neurotoxicity, and transaminitis. Administration of GEMOX on 2 days (days 1 and 8) was reason for more myelosuppression (38%) seen in them GEMOX arm. In our study mGEMOX was used in which gemcitabine (800 mg/m 2 ) and oxaliplatine

(80 mg/m 2 ) were used for 2 weekly maximum six cycles. There was no toxic death and a greater number of patients could complete mGEMOX therapy; transaminitis was significantly more common in mGEMOX arm. Riechelmnn et al. [21] It is comparable to other gemcitabine-based studies. [7],[8],[9],[12],[17] Andre et al., [22] recently reported a phase II trial of biliary tract cancer. In our analysis, the objective response rates for GBC was only 4.3% and OS and PFS for the whole group were 8.8 and 3.4 months, respectively. CCT with mGEMOX and with radiotherapy has helped in improving the OS and PFS in few patients who had good performance status. BSC remains important integral in management of carcinoma gallbladder.


  Conclusion Top


In summary, carcinoma gallbladder remains a lethal malignancy, in majority of patients who presented with advance stage, surgery was not possible and palliative treatment was the only option. Our survival and progression free survival are similar to those as reported in literature. Our series suggests that used of BSC along with chemotherapy and or with radiotherapy may help in increase in period of stable disease along with OS in selected group. Chemotherapy with GEMOX and or with radiotherapy has helped in improving the OS and progression free survival in some patients who had good performance status.

 
  References Top

1.National Cancer Registry Program: Consolidated report of Population Based Cancer Registries 2001-2004. Indian Council of Medical Research Publication. Available from: http://www.icmr.nic.in/ncrp/report_pop_2001-04/cancer_p_based.htm [Last accessed date on 2013 Aug 18]. cancer P based.htm. 2004;328:323-324. 23.  Back to cited text no. 1
    
2.Lazcano-Ponce EC, Miquel JF, Mun˜oz N, Herrero R, Ferrecio C, Wistuba II, et al. Epidemiology and molecular pathology of gall bladder cancer. CA Cancer J Clin 2001;51:349.Kataki AC, Sharma JD. First Report of the Population Based Cancer Registries Under North Eastern Regional Cancer Registry   Back to cited text no. 2
    
3.2003-2004. [Last accessed date on 2013 Aug 18].  Back to cited text no. 3
    
4.Takada T, Kato H, Matsushiro T, Nimura Y, Nagakawa T, Nakayama T. Comparison of 5-fluorouracil, doxorubicin, and mitomycin with 5-fluorouracil alone in the treatment of pancreatic-biliary carcinomas. Oncology 1994;51:396-400.  Back to cited text no. 4
    
5.Okusaka T, Ishii H, Funakoshi A, Yamao K, Ohkawa S, Saito S, et al. Phase II study of single agent gemcitabine in patients with advanced biliary tract cancer. Cancer Chemother Pharmacol 2006;57:647-53.  Back to cited text no. 5
    
6.Sharma A, Bedi R, Shukla NK. Does chemotherapy improves survival in gall bladder cancer? J Clin Oncol 2004;22:363s.  Back to cited text no. 6
    
7.Hsu C, Shen YC, Yang CH, Yeh KH, Lu YS, Hsu CH, et al. Weekly gemcitabine plus 24 hour infusion of 5-fluourouracil/leucovorin for locally advanced or metastatic carcinoma of biliary tract. Br J Cancer 2004;90:1715-9.  Back to cited text no. 7
    
8.Doval DC, Shekhon JS, Gupta SK, Fuloria J, Shukla VK, Gupta S, et al. A phase II study of gemcitabine and cisplatin in chemotherapy naïve, unresectable gall bladder cancer. Br J Cancer 2004;90:1516-20.  Back to cited text no. 8
    
9.AndrexT, Tournigand C, Rosmorduc O, Provent S, Maindrault-Goebel F, Avenin D, et al. GERCOR Group. Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: A GERCOR study. Ann Oncol 2004;15:1339-43.  Back to cited text no. 9
    
10.Takada T, Nimura Y, Katoh H, Nagakawa T, Nakayama T, MatsushiroT, et al. Prospective randomized trial of 5 fluorouracil, doxorubicin, and mitomycin C for non respectable pancreatic and biliary carcinoma: Multicenter randomized trial. Hepatogastroenterology 1998;45:2020-6.  Back to cited text no. 10
    
11.Perpetuo MD, Valdivieso M, Heilbrun LK, Nelson RS, Connor T, Bodey GP. Natural history study of gallbladder cancer: A review of 36 years experience at M.D. Anderson Hospital and Tumor Institue. Cancer 1978;42:330-5.  Back to cited text no. 11
    
12.Sharma A, Mohanti B, Raina V, Shukla N, Pal S, Dwary A, et al. A phase II study of gemcitabine and oxaliplatin (OXIGEM) in unresectable gall bladder cancer. Cancer Chemother Pharmacol 2010;65:497-502.  Back to cited text no. 12
    
13.Gallardo J, Fodor M, Gamargo C, Orlandi L. Efficacy of gemcitabine in the treatment of patients with gallbladder: A case report. Cancer 1998;83:2419-21.  Back to cited text no. 13
[PUBMED]    
14.Castro MP. Efficacy of gemcitabine in the treatment of patients with gallbladder: A case report. Cancer 1998;82:639-41.  Back to cited text no. 14
[PUBMED]    
15.Gallardo JO, Rubio B, Fodor M, Orlandi L, Yáñez M, Gamargo C, et al. A phase II study of gemcitabine in gall bladder carcinoma. Ann Oncol 2001;12:1403-6.  Back to cited text no. 15
    
16.Thongprasert S, Napapan S, Charoentum C, Moonprakan S. Phase II study of gemcitabine and cisplatin as first line chemotherapy in inoperable biliary tract carcinoma. Ann Oncol 2005;16:279-81.  Back to cited text no. 16
    
17.Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:1273-81.  Back to cited text no. 17
[PUBMED]    
18.Harder J, Riecken B, Kummer O, Lohrmann C, Otto F, Usadel H, et al. Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer. Br J Cancer 2006;95:848-52.  Back to cited text no. 18
    
19.Louvet C, AndrexT, Lledo G, Hammel P, Bleiberg H, Bouleuc C, et al. Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: Final results of a GERCOR multicenterphase II study. J Clin Oncol 2002;20:1512-8.  Back to cited text no. 19
    
20.Glimelius B, Hoffman K, Sjo¨de×n PO, Jacobsson G, Sellström H, Enander LK, et al. Chemotherapy improves survival and quality of life in pancreatic and biliary tract cancer. Ann Oncol 1996;7:593-600.  Back to cited text no. 20
    
21.Riechelmnn RP, Townsley CA, Chin SN, Pond GR, Knox JJ. Expanded phase II trial of gemcitabine and capecitabine for advanced biliary tract cancer. Cancer 2007;110:1307-12.  Back to cited text no. 21
    
22.Andre′ T, Reyes-Vidal JM, Fartoux L, Ross P, Leslie M, Rosmorduc O, et al. Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: A phase II study. Br J Cancer 2008;99:862-7.  Back to cited text no. 22
    


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