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Erschienen in: Supportive Care in Cancer 6/2017

04.02.2017 | Original Article

Treatment of pancreatic insufficiency using pancreatic extract in patients with advanced pancreatic cancer: a pilot study (PICNIC)

verfasst von: Nicholas Zdenkowski, George Radvan, Leanna Pugliese, Julie Charlton, Christopher Oldmeadow, Allison Fraser, Antonino Bonaventura

Erschienen in: Supportive Care in Cancer | Ausgabe 6/2017

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Abstract

Purpose

Survival with advanced pancreatic cancer is less than 12 months. Pancreatic exocrine insufficiency may contribute to pancreatic cancer-related cachexia, via nutrient malabsorption. We aimed to determine the feasibility of prescribing pancreatic extract (Creon®) for patients with advanced pancreatic cancer.

Methods

Patients with advanced pancreatic cancer, without frank malabsorption, were randomised in this feasibility study to pancreatic extract 50,000 units with meals and 25,000 units with snacks, or placebo. Standardised dietary advice was given. Anti-cancer and supportive care treatments were permitted. Outcomes included weight, body mass index (BMI), quality of life (QLQC30, PAN26), survival and nutritional assessment (PG-SGA).

Results

Eighteen patients were randomised before study closure due to slow recruitment. Baseline characteristics were well matched. Weight loss prior to randomisation was numerically greater in the pancreatic extract group (mean 0.7 vs 2.2 kg). Weight loss was numerically greater in the placebo group, however not significantly. No differences in BMI or nutrition score were seen. Quality of life did not differ between study groups. Median overall survival was 17 (95% CI 8.1–48.7) weeks in the control group, and 67.6 (95% CI 14.1–98.4) weeks in the pancreatic extract group (p = 0.1063). Only 17% (18/106) of potentially eligible patients were recruited, related to patient/family reluctance, rapid clinical deterioration and patients already prescribed pancreatic extract. A moderate pill burden was noted.

Conclusion

Despite intriguing survival results, this study was not sufficiently feasible to proceed to a fully powered comparative study. A multi-centre study would be required to exclude a significant difference in outcomes.
Literatur
1.
Zurück zum Zitat Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825. doi:10.1056/NEJMoa1011923 CrossRefPubMed Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825. doi:10.​1056/​NEJMoa1011923 CrossRefPubMed
2.
Zurück zum Zitat Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. doi:10.1002/ijc.29210 CrossRefPubMed Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. doi:10.​1002/​ijc.​29210 CrossRefPubMed
3.
Zurück zum Zitat Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H (2013) Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. J Am Med Assoc 310(14):1473–1481. doi:10.1001/jama.2013.279201 CrossRef Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H (2013) Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. J Am Med Assoc 310(14):1473–1481. doi:10.​1001/​jama.​2013.​279201 CrossRef
5.
Zurück zum Zitat Domínguez-Muñoz JE, Nieto-Garcia L 2013 Iglesias-Garcia J Impact of diagnosis and treatment of pancreatic exocrine insufficiency (PEI) on survival of patients with unresectable pancreatic cáncer (PC) In: vol 3 (suppl). Pancreatology, p S80 Domínguez-Muñoz JE, Nieto-Garcia L 2013 Iglesias-Garcia J Impact of diagnosis and treatment of pancreatic exocrine insufficiency (PEI) on survival of patients with unresectable pancreatic cáncer (PC) In: vol 3 (suppl). Pancreatology, p S80
6.
Zurück zum Zitat Davidson W, Ash S, Capra S, Bauer J (2004) Weight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer. Clin Nutr 23(2):239–247CrossRefPubMed Davidson W, Ash S, Capra S, Bauer J (2004) Weight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer. Clin Nutr 23(2):239–247CrossRefPubMed
8.
9.
Zurück zum Zitat Sikkens EC, Cahen DL, de Wit J, Looman CW, van Eijck C, Bruno MJ (2014) A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor. J Clin Gastroenterol 48(5):e43–e46. doi:10.1097/MCG.0b013e31829f56e7 PubMed Sikkens EC, Cahen DL, de Wit J, Looman CW, van Eijck C, Bruno MJ (2014) A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor. J Clin Gastroenterol 48(5):e43–e46. doi:10.​1097/​MCG.​0b013e31829f56e7​ PubMed
10.
Zurück zum Zitat Smith RC, Smith SF, Wilson J, Pearce C, Wray N, Vo R, Chen J, Ooi CY, Oliver M, Katz T, Turner R, Nikfarjam M, Rayner C, Horowitz M, Holtmann G, Talley N, Windsor J, Pirola R, Neale R (2016) Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency. Pancreatology: official journal of the International Association of Pancreatology (IAP) [et al.] 16(2):164–180. doi:10.1016/j.pan.2015.12.006 CrossRef Smith RC, Smith SF, Wilson J, Pearce C, Wray N, Vo R, Chen J, Ooi CY, Oliver M, Katz T, Turner R, Nikfarjam M, Rayner C, Horowitz M, Holtmann G, Talley N, Windsor J, Pirola R, Neale R (2016) Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency. Pancreatology: official journal of the International Association of Pancreatology (IAP) [et al.] 16(2):164–180. doi:10.​1016/​j.​pan.​2015.​12.​006 CrossRef
11.
Zurück zum Zitat Bruno MJ, Haverkort EB, Tijssen GP, Tytgat GN, van Leeuwen DJ (1998) Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut 42(1):92–96CrossRefPubMedPubMedCentral Bruno MJ, Haverkort EB, Tijssen GP, Tytgat GN, van Leeuwen DJ (1998) Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut 42(1):92–96CrossRefPubMedPubMedCentral
12.
13.
Zurück zum Zitat Fitzsimmons D, Kahl S, Butturini G, van Wyk M, Bornman P, Bassi C, Malfertheiner P, George SL, Johnson CD (2005) Symptoms and quality of life in chronic pancreatitis assessed by structured interview and the EORTC QLQ-C30 and QLQ-PAN26. Am J Gastroenterol 100(4):918–926CrossRefPubMed Fitzsimmons D, Kahl S, Butturini G, van Wyk M, Bornman P, Bassi C, Malfertheiner P, George SL, Johnson CD (2005) Symptoms and quality of life in chronic pancreatitis assessed by structured interview and the EORTC QLQ-C30 and QLQ-PAN26. Am J Gastroenterol 100(4):918–926CrossRefPubMed
14.
Zurück zum Zitat Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, JMd, Kaasa S, Klee M, Osoba D, Razavi D, Rofe PB, Schraub S, Sneeuw K, Sullivan M, Takeda F (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85(5):365–376. doi:10.1093/jnci/85.5.365 CrossRefPubMed Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, JMd, Kaasa S, Klee M, Osoba D, Razavi D, Rofe PB, Schraub S, Sneeuw K, Sullivan M, Takeda F (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85(5):365–376. doi:10.​1093/​jnci/​85.​5.​365 CrossRefPubMed
16.
17.
Zurück zum Zitat Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12(5):489–495. doi:10.1016/s1470-2045(10)70218-7 CrossRefPubMed Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12(5):489–495. doi:10.​1016/​s1470-2045(10)70218-7 CrossRefPubMed
18.
Zurück zum Zitat Blum D, Stene GB, Solheim TS, Fayers P, Hjermstad MJ, Baracos VE, Fearon K, Strasser F, Kaasa S (2014) Validation of the consensus-definition for cancer cachexia and evaluation of a classification model–a study based on data from an international multicentre project (EPCRC-CSA). Ann Oncol 25(8):1635–1642. doi:10.1093/annonc/mdu086 CrossRefPubMed Blum D, Stene GB, Solheim TS, Fayers P, Hjermstad MJ, Baracos VE, Fearon K, Strasser F, Kaasa S (2014) Validation of the consensus-definition for cancer cachexia and evaluation of a classification model–a study based on data from an international multicentre project (EPCRC-CSA). Ann Oncol 25(8):1635–1642. doi:10.​1093/​annonc/​mdu086 CrossRefPubMed
19.
Zurück zum Zitat Whitcomb DC, Lehman GA, Vasileva G, Malecka-Panas E, Gubergrits N, Shen Y, Sander-Struckmeier S, Caras S (2010) Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. Am J Gastroenterol 105(10):2276–2286. doi:10.1038/ajg.2010.201 CrossRefPubMed Whitcomb DC, Lehman GA, Vasileva G, Malecka-Panas E, Gubergrits N, Shen Y, Sander-Struckmeier S, Caras S (2010) Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. Am J Gastroenterol 105(10):2276–2286. doi:10.​1038/​ajg.​2010.​201 CrossRefPubMed
20.
Zurück zum Zitat Toouli J, Biankin AV, Oliver MR, Pearce CB, Wilson JS, Wray NH (2010) Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations. Med J Aust 193(8):461–467PubMed Toouli J, Biankin AV, Oliver MR, Pearce CB, Wilson JS, Wray NH (2010) Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations. Med J Aust 193(8):461–467PubMed
21.
Zurück zum Zitat Bye A, Wesseltoft-Rao N, Iversen PO, Skjegstad G, Holven KB, Ulven S, Hjermstad MJ (2016) Alterations in inflammatory biomarkers and energy intake in cancer cachexia: a prospective study in patients with inoperable pancreatic cancer. Med Oncol 33(6):54. doi:10.1007/s12032-016-0768-2 CrossRefPubMed Bye A, Wesseltoft-Rao N, Iversen PO, Skjegstad G, Holven KB, Ulven S, Hjermstad MJ (2016) Alterations in inflammatory biomarkers and energy intake in cancer cachexia: a prospective study in patients with inoperable pancreatic cancer. Med Oncol 33(6):54. doi:10.​1007/​s12032-016-0768-2 CrossRefPubMed
22.
Zurück zum Zitat Ozola Zalite I, Zykus R, Francisco Gonzalez M, Saygili F, Pukitis A, Gaujoux S, Charnley RM, Lyadov V (2015) Influence of cachexia and sarcopenia on survival in pancreatic ductal adenocarcinoma: a systematic review. Pancreatology : official journal of the International Association of Pancreatology (IAP) [et al.] 15(1):19–24. doi:10.1016/j.pan.2014.11.006 CrossRef Ozola Zalite I, Zykus R, Francisco Gonzalez M, Saygili F, Pukitis A, Gaujoux S, Charnley RM, Lyadov V (2015) Influence of cachexia and sarcopenia on survival in pancreatic ductal adenocarcinoma: a systematic review. Pancreatology : official journal of the International Association of Pancreatology (IAP) [et al.] 15(1):19–24. doi:10.​1016/​j.​pan.​2014.​11.​006 CrossRef
23.
Zurück zum Zitat Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O'Reilly DS, Foulis AK, Horgan PG, McMillan DC (2011) A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. Eur J Cancer 47(17):2633–2641. doi:10.1016/j.ejca.2011.03.028 CrossRefPubMed Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O'Reilly DS, Foulis AK, Horgan PG, McMillan DC (2011) A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. Eur J Cancer 47(17):2633–2641. doi:10.​1016/​j.​ejca.​2011.​03.​028 CrossRefPubMed
24.
Zurück zum Zitat Togashi Y, Kogita A, Sakamoto H, Hayashi H, Terashima M, de Velasco MA, Sakai K, Fujita Y, Tomida S, Kitano M, Okuno K, Kudo M, Nishio K (2015) Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer. Cancer Lett 356(2 Pt B):819–827. doi:10.1016/j.canlet.2014.10.037 CrossRefPubMed Togashi Y, Kogita A, Sakamoto H, Hayashi H, Terashima M, de Velasco MA, Sakai K, Fujita Y, Tomida S, Kitano M, Okuno K, Kudo M, Nishio K (2015) Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer. Cancer Lett 356(2 Pt B):819–827. doi:10.​1016/​j.​canlet.​2014.​10.​037 CrossRefPubMed
26.
Zurück zum Zitat Gartner S, Kruger J, Aghdassi AA, Steveling A, Simon P, Lerch MM, Mayerle J (2016) Nutrition in pancreatic cancer: a review. Gastrointestinal tumors 2(4):195–202. doi:10.1159/000442873 Gartner S, Kruger J, Aghdassi AA, Steveling A, Simon P, Lerch MM, Mayerle J (2016) Nutrition in pancreatic cancer: a review. Gastrointestinal tumors 2(4):195–202. doi:10.​1159/​000442873
27.
Zurück zum Zitat Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, Baracos VE (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9(7):629–635. doi:10.1016/s1470-2045(08)70153-0 Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, Baracos VE (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9(7):629–635. doi:10.​1016/​s1470-2045(08)70153-0
28.
Zurück zum Zitat Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grutzmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM, Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, Grimmond SM (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531(7592):47–52. doi:10.1038/nature16965 CrossRefPubMed Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grutzmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM, Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, Grimmond SM (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531(7592):47–52. doi:10.​1038/​nature16965 CrossRefPubMed
Metadaten
Titel
Treatment of pancreatic insufficiency using pancreatic extract in patients with advanced pancreatic cancer: a pilot study (PICNIC)
verfasst von
Nicholas Zdenkowski
George Radvan
Leanna Pugliese
Julie Charlton
Christopher Oldmeadow
Allison Fraser
Antonino Bonaventura
Publikationsdatum
04.02.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Supportive Care in Cancer / Ausgabe 6/2017
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-017-3602-2

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