|Year : 2015 | Volume
| Issue : 3 | Page : 449-452
Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center
B Sirohi1, S Dawood2, S Rastogi1, A Pandey1, M Bal3, N Shetty4, SV Shrikhande5
1 Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
2 Department of Medical Oncology, Dubai Hospital, UAE
3 Department of Pathology, Tata Memorial Centre, Mumbai, Maharashtra, India
4 Department of Radiology, Tata Memorial Centre, Mumbai, Maharashtra, India
5 Department of Gastrointestinal and Hepatopancreatobiliary Surgery, Tata Memorial Centre, Mumbai, Maharashtra, India
|Date of Web Publication||18-Feb-2016|
Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: The aim of this study was to look at the outcome of patients with metastatic pancreatic cancer treated at a tertiary cancer center in India. Patients And Methods: A total of 101 patients with locally advanced and metastatic pancreatic cancer diagnosed between May 2012 and July 2013 were identified from a prospectively maintained database at the tertiary cancer center. Overall survival (OS) was computed using the Kaplan–Meir product limit method and compared across groups using the log-rank statistics. Cox proportional hazards model, adjusted for a number of patient and tumor characteristics, was then used to determine factors prognostic for OS. Results: Median age at diagnosis was 55 years (range: 21–81 years). 57.4% (n = 58) of patients were male, 22% (n = 22) had performance status (PS) of <2 at diagnosis and 89% received first-line chemotherapy, while the rest received best supportive care. For the whole cohort, 6 month and 1-year OS was 57% (95% confidence interval [CI]: 46–66%) and 47% (95% CI: 35–57%), respectively. In a multivariable model, PS <2 and oligometastatic disease were associated with a significantly decreased risk of death. Conclusion: Results from our analysis indicate that the prognostic outcome among Indian patients with metastatic pancreatic cancer is poor with survival outcomes similar to those reported in North America and Europe.
Keywords: Chemotherapy, pancreatic cancer, prognostic factors
|How to cite this article:|
Sirohi B, Dawood S, Rastogi S, Pandey A, Bal M, Shetty N, Shrikhande S V. Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center. Indian J Cancer 2015;52:449-52
|How to cite this URL:|
Sirohi B, Dawood S, Rastogi S, Pandey A, Bal M, Shetty N, Shrikhande S V. Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center. Indian J Cancer [serial online] 2015 [cited 2019 Jun 27];52:449-52. Available from: http://www.indianjcancer.com/text.asp?2015/52/3/449/176732
| » Introduction|| |
Pancreatic cancer has the lowest survival by stage compared with any other solid tumor and is currently the eighth leading cause of cancer-related mortality worldwide. In the year 2014, it is estimated that 46,420 new cases of pancreatic cancer will be diagnosed in the United States, and this would be associated with approximately 39,590 deaths from this disease-making pancreatic cancer the fourth leading cause of cancer-related death in the United States. There is no representative data on pancreatic cancer from India.
The natural history of this disease is typically associated with early loco regional spread and distant metastasis and as a consequence, the majority of patients at presentation have either unresectable locally advanced disease or metastatic disease making treatment measures purely palliative in nature.
Until the last decade, single agent gemcitabine was the standard treatment for patients with either locally advanced or metastatic pancreatic cancer having demonstrated an improved overall survival (OS) compared to fluorouracil. However, despite the improvement in OS observed objective responses with single agent gemcitabine were <10% with median OS also being abysmal at approximately 6 months. The last decade has seen some significant advances in both the systemic chemotherapeutic management of this disease together with a deeper understanding of the biology underlying this aggressive disease. The combination of gemcitabine-erlotinib, gemcitabine-nab-paclitaxel, and FOLFIRINOX has all been shown in randomized clinical trials to be superior to single agent gemcitabine.,, However, the gains in survival with these combinations compared to single agent gemcitabine are still modest with OS ranging from 6 to 11 months. These modest gains have been hampered by the significant cost increase associated with combination therapies both in terms of monetary costs and terms of impact of on quality of life due to increased adverse side effect profiles of the combination regimens.
Data pertaining to the outcome of patients with locally advanced or metastatic pancreatic cancer in India are currently lacking though data on surgical outcomes have been published., Using a prospectively maintained database, the objective of this study was to look at the treatment practices and associated prognostic outcome of patients with unresectable locally advanced or metastatic pancreatic cancer treated at the tertiary cancer center in India.
| » Patients and Methods|| |
This study utilized a prospectively maintained database at the tertiary cancer center in India. Patients with locally advanced or metastatic adenocarcinoma of the pancreas diagnosed between May 2012 and July 2013 were included. Patients with more than one primary were excluded. Variables recorded for analysis included age at diagnosis, sex, stage of disease, first-line treatment, associated co-morbidities, and levels of baseline tumor markers.
Patient and tumor characteristics were tabulated. The primary end point of this study was OS that was calculated from the date of diagnosis to the date of death from any cause or last follow-up. Unadjusted 6 month OS was computed using the Kaplan–Meir product limit method and compared across groups using log-rank statistic. Multivariable cox proportional hazards models were then fit to look at the association of patient and tumor characteristics and OS, and results were expressed in hazard ratios (HRs) and 95% confidence intervals (CIs). Variables selected to be included in the model were based on clinical significance rather than statistical significance. P < 0.05 were considered as statistically significant with all tests being two-sided. For this study, we used SAS 9.2 (SAS Institute, Cary, NC, United States) version for statistical analysis.
| » Results|| |
Patient and tumor characteristics
[Table 1] summarizes the patient and tumor characteristics of the cohort studied. The final analysis included 101 patients with locally advanced or metastatic pancreatic cancer. Median age of diagnosis was 55 years (range: 21–81 years). Fifty-eight (57.4%) patients were male and 43 (42.6%) patient were female. Fifteen (14.8%) patients had locally advanced disease, while 86 (85.2%) had metastatic disease at presentation. Twenty-two (22%) patients had an Eastern Cooperative Oncology Group (ECOG) of <2 at presentation, while 78 (78%) patients had an ECOG of ≥2. [Table 2] summarizes first-line treatment received by patients with locally advanced or metastatic pancreatic cancer. Eleven patients (10.9%) were not candidates for chemotherapy and received upfront palliative care. The majority of patients who were candidates for chemotherapy received either single agent gemcitabine or a combination of gemcitabine and another agent such as oxaliplatin, capecitabine, or nab-paclitaxel. Seven (6.9%) patients received upfront FOLFIRINOX. Twelve (11.9%) patients received chemoradiation therapy as first-line therapy.
|Table 1: Patient and tumor characteristics among patients with locally advanced and metastatic pancreatic cancer|
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[Table 3] summarizes the unadjusted 6 month OS. For the whole cohort, 6 month and 1-year OS was 57% (95% CI: 46%–66%) and 47% (95% CI: 35%–57%), respectively. Six month OS was 61% and 51% among male and female patients, respectively (P = 0.225). Six month OS was significantly higher among patients who had a normal baseline carcinoembryonic antigen (CEA) compared with those with elevated CEA (80% vs. 51%, P = 0.039). A baseline ECOG of <2, history of prior surgery, and age <55 years at presentation were also associated with significant improvement in 6 month OS. [Figure 1] shows that Kaplan–Meier curves for OS among the whole cohort, stratified by baseline CEA level, stratified by baseline PS, and stratified by sex.
|Figure 1: The Kaplan Meier curves for overall survival among (a) the whole cohort, (b) stratified by baseline CEA level, (c) stratified by baseline performance status, (d) stratified by sex|
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Multivariable logistic regression models
[Table 4] summarizes the results of the multivariable cox proportional hazards model. Compared to patients with ECOG <2 those with ECOG ≥2 had a significantly higher risk of death (HR: 10.06, 95% CI: 3.34–30.26, P < 0.001). Patients with oligometastatic disease had lower risk of death compared with those with more than one metastatic lesion (HR: 0.38, 95% CI: 0.15–0.97, P = 0.044). A strong trend toward worse survival was observed among patients with elevated baseline CEA level compared with those with normal baseline CEA level (HR = 2.46, 95% CI: 0.97–6.24, P = 0.05) although this was not statistically significant.
| » Discussion|| |
Data on prognostic outcome of patients with locally advanced or metastatic pancreatic cancer treated in India are lacking. Data collected in our study reveal a 6-month and 1-year OS of 57% and 47%, respectively. Six month OS of 57%, 67%, and 75% have been reported among patients with metastatic pancreatic cancer enrolled in randomized clinical trials receiving single agent gemcitabine, gemcitabine, and nab-paclitaxel combination and FOLFIRINOX, respectively.,, Similarly, 1-year OS of 20.6%, 35%, and 48% have been reported in these cohorts of patients receiving single agent gemcitabine, gemcitabine, and nab-paclitaxel combination and FOLFIRINOX, respectively.,, These clinical trials enrolled patients largely from North America and Europe. Our results from India, where patients received a variety of chemotherapy regimens (the majority of which were gemcitabine-based) are similar to these results indicating that metastatic pancreatic cancer in India has a similar abysmal prognosis as that among patients diagnosed in North America and Europe.
The data for this study arose from a cohort of patients diagnosed from May 2012 to July 2013. Although nab-paclitaxel received approval from the Food and Drug Administration in September 2013, data pertaining to the use of FOLFIRINOX among patients with metastatic pancreatic cancer was published in 2011. Conroy et al. reported on the results of the phase III ACCORD trial that randomized patients with metastatic pancreatic cancer to receive either single agent gemcitabine or FOLFIRINOX. The authors reported a significant improvement in median OS from 6.8 months to 11.1 months and a significant improvement in objective response from 9% to 32% favoring patients receiving FOLFIRINOX. Despite these results, only seven (6.9%) patients received this regimen. Several reasons may explain the lack of use of this regimen among Indian patients. First, the ACCORD 11 trial enrolled patients with relatively good PS with ECOG 0 and 1 thereby effectively restricting the type of patients that can receive this regimen. Second, the FOLFIRINOX regimen is associated with significant adverse effects compared to gemcitabine including increased grade 3/4 neutropenia (46% vs. 21%), increased febrile neutropenia (5.4% vs. 1.2%) as well as significant increased incidence of vomiting, fatigue, and diarrhea. The adverse side effect profile may presumably impact a physician's decision to use FOLFIRINOX among patients with metastatic pancreatic cancer where maintaining quality of life is a more important endpoint compared to survival. Interestingly, Gourgou-Bourgade et al. looked at the impact of FOLFIRINOX compared to gemcitabine on the quality of life of patients with metastatic pancreatic cancer enrolled on the ACCORD 11 trial and reported that FOLFIRINOX significantly reduces the quality of life impairment compared with gemcitabine. Third, the monetary cost related to delivering FOLFIRINOX and treating the associated side effects may also be a contributing factor to the decision-making process when choosing the type of regimen to use in this cohort of patients.
There have been multiple studies exploring prognostic factors in pancreatic cancer. Most of these studies are retrospective in nature with small sample size. Though in the multivariate analysis, age was not a significant factor in our study, data regarding prognostic impact of age are controversial with some studies showing it to be an independent prognostic factor  while others do not identify it as prognostic factor. Similarly, Carbohydrate antigen 19.9 has been found to be prognostic factor in most of the studies ,,,, but not all  as has been the case in our study also. Tumor markers may not be prognostic as they can be increased in various benign etiologies also. PS has been consistently shown to influence survival in various studies., Tas et al. showed its influence on prognosis in all stages of pancreatic cancer. The negative prognosis is possibly due to most patients being older, jaundice, and anemia and/or decreased chemotherapy response in patients with poor PS. Unlike breast cancer, oligometastasis in pancreatic cancer has not been shown to be prognostic, but our study showed that they had a better prognosis probably due to a better biology and limited tumor burden.
| » Conclusion|| |
Outcome of advanced pancreatic cancer is poor in our patient population also. We have a substantial fraction of patients with poor PS. In this study, we demonstrated that the ECOG PS and burden of disease are the major prognostic factors influencing survival at all stages of pancreatic cancer in Indian patients.
| » References|| |
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29.
Burris HA 3rd
, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al
.: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. Journal of clinical oncology: Official journal of the American Society of Clinical Oncology 1997, 15 (6):2403-2413.
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al.
Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007;25:1960-6.
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al.
Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-703.
Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al.
FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-25.
Shrikhande SV, Barreto SG, Somashekar BA, Suradkar K, Shetty GS, Talole S, Sirohi B, Goel M, Shukla PJ: Evolution of pancreatoduodenectomy in a tertiary cancer center in India: Improved results from service reconfiguration. Pancreatology: Official journal of the International Association of Pancreatology
2013, 13 (1):63-71.
Shrikhande SV, Barreto SG, Bodhankar YD, Suradkar K, Shetty G, Hawaldar R, Goel M, Shukla PJ: Superior mesenteric artery first combined with uncinate process approach versus uncinate process first approach in pancreatoduodenectomy: A comparative study evaluating perioperative outcomes. Langenbeck's archives of surgery/Deutsche Gesellschaft fur Chirurgie
2011, 396 (8):1205-1212.
Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, Ychou M, Bouché O, Guimbaud R, et al.
Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: Results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol 2013;31:23-9.
Stocken DD, Hassan AB, Altman DG, Billingham LJ, Bramhall SR, Johnson PJ, et al.
Modelling prognostic factors in advanced pancreatic cancer. Br J Cancer 2008;99:883-93.
Tas F, Sen F, Keskin S, Kilic L, Yildiz I. Prognostic factors in metastatic pancreatic cancer: Older patients are associated with reduced overall survival. Mol Clin Oncol 2013;1:788-92.
Papadoniou N, Kosmas C, Gennatas K, Polyzos A, Mouratidou D, Skopelitis E, et al.
Prognostic factors in patients with locally advanced (unresectable) or metastatic pancreatic adenocarcinoma: A retrospective analysis. Anticancer Res 2008;28:543-9.
Park JK, Yoon YB, Kim YT, Ryu JK, Yoon WJ, Lee SH. Survival and prognostic factors of unresectable pancreatic cancer. J Clin Gastroenterol 2008;42:86-91.
An X, Li YH, Lin XB, Wang FH, Feng F, Xu RH, et al.
[Prognostic value of serum CA19-9 in patients with advanced pancreatic cancer receiving gemcitabine based chemotherapy]. Ai Zheng 2009;28:286-91.
Howaizi M, Abboura M, Krespine C, Sbai-Idrissi MS, Marty O, Djabbari-Sobhani M. A new cause for Carbohydrate antigen 19.9 elevation: Heavy tea consumption. Gut 2003;52:913-4.
Krishnan S, Rana V, Janjan NA, Abbruzzese JL, Gould MS, Das P, et al.
Prognostic factors in patients with unresectable locally advanced pancreatic adenocarcinoma treated with chemoradiation. Cancer 2006;107:2589-96.
Weber A, Kehl V, Mittermeyer T, Herberich E, Röthling N, Schmid RM, et al.
Prognostic factors for survival in patients with unresectable pancreatic cancer. Pancreas 2010;39:1247-53.
Tas F, Sen F, Odabas H, Kilic L, Keskin S, Yildiz I. Performance status of patients is the major prognostic factor at all stages of pancreatic cancer. Int J Clin Oncol 2013;18:839-46.
Di Lascio S, Pagani O. Oligometastatic breast cancer: A shift from palliative to potentially curative treatment? Breast Care (Basel) 2014;9:7-14.
[Table 1], [Table 2], [Table 3], [Table 4]