Use and outcomes from neoadjuvant chemotherapy in borderline resectable pancreatic ductal adenocarcinoma in an Australasian population.
drug therapy
general surgery
mortality
neoadjuvant therapy
pancreatic neoplasms
Journal
Asia-Pacific journal of clinical oncology
ISSN: 1743-7563
Titre abrégé: Asia Pac J Clin Oncol
Pays: Australia
ID NLM: 101241430
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
25
01
2022
accepted:
13
06
2022
pubmed:
15
7
2022
medline:
20
1
2023
entrez:
14
7
2022
Statut:
ppublish
Résumé
Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable METHOD: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan-Meier analysis. The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p = .01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR) .3, p < .0001). NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.
Sections du résumé
BACKGROUND
BACKGROUND
Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable METHOD: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan-Meier analysis.
RESULTS
RESULTS
The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p = .01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR) .3, p < .0001).
CONCLUSIONS
CONCLUSIONS
NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.
Substances chimiques
Gemcitabine
0
Deoxycytidine
0W860991D6
Fluorouracil
U3P01618RT
Leucovorin
Q573I9DVLP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
214-225Subventions
Organisme : Hemstritch Foundation
Organisme : Pancare Foundation
Organisme : Jreissati Foundation and Segal Foundation
Informations de copyright
© 2022 John Wiley & Sons Australia, Ltd.
Références
Australian Institute of Health and Welfare. Cancer in Australia 2019. https://www.aihw.gov.au/reports/cancer/cancer-in-australia-2019. Accessed 3 May 2020.
Australian Bureau of Statistics. Leading causes of death, Australia-selected years- 2009, 2013, 2018. Australian Bureau of Statistics. https://www.abs.gov.au/ausstats/abs@.nsf/0/47E19CA15036B04BCA2577570014668B?Opendocument. Accessed 3 May 2020.
Ducreux M, Committee obotEG, Cuhna AS, et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(suppl_5):v56-v68.
Huang L, Jansen L, Balavarca Y, et al. Stratified survival of resected and overall pancreatic cancer patients in Europe and the USA in the early twenty-first century: a large, international population-based study. BMC Med. 2018;16(1):125.
Neoptolemos JP, Stocken DD, Dunn JA, et al. Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg. 2001;234(6):758-768.
Pingpank JF, Hoffman JP, Ross EA, et al. Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas. J Gastrointest Surg. 2001;5(2):121-130.
Krishnan S, Rana V, Janjan NA, et al. Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer. 2007;110(1):47-55.
Balaban EP, Mangu PB, Khorana AA, et al. Locally advanced, unresectable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34(22):2654-2668.
Tummala P, Howard T, Agarwal B. Dramatic survival benefit related to R0 resection of pancreatic adenocarcinoma in patients with tumor ≤25 mm in size and ≤1 involved lymph nodes. Clin Transl Gastroenterol. 2013;4(3):e33.
Versteijne E, Suker M, Groothuis K, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the Dutch Randomized Phase III PREOPANC trial. J Clin Oncol. 2020:Jco1902274.
Pietrasz D, Turrini O, Vendrely V, et al. How does chemoradiotherapy following induction FOLFIRINOX improve the results in resected borderline or locally advanced pancreatic adenocarcinoma? An AGEO-FRENCH Multicentric Cohort. Ann Surg Oncol. 2019;26(1):109-117.
Murphy JE, Wo JY, Ryan DP, et al. Total neoadjuvant therapy with FOLFIRINOX followed by individualized chemoradiotherapy for borderline resectable pancreatic adenocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2018;4(7):963-969.
Versteijne E, Vogel JA, Besselink MG, et al. Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg. 2018;105(8):946-958.
Sadot E, Doussot A, O'Reilly EM, et al. FOLFIRINOX induction therapy for stage 3 pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22(11):3512-3521.
Stein SM, James ES, Deng Y, et al. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Br J Cancer. 2016;114(7):737-743.
Mellon EA, Hoffe SE, Springett GM, et al. Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma. Acta Oncol. 2015;54(7):979-985.
Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant modified FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol. 2015;22(4):1153-1159.
Marthey L, Sa-Cunha A, Blanc JF, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort. Ann Surg Oncol. 2015;22(1):295-301.
Boone BA, Steve J, Krasinskas AM, et al. Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. J Surg Oncol. 2013;108(4):236-241.
Hosein PJ, Macintyre J, Kawamura C, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199.
Andriulli A, Festa V, Botteri E, et al. Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol. 2012;19(5):1644-1662.
Stokes JB, Nolan NJ, Stelow EB, et al. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol. 2011;18(3):619-627.
Cardenes HR, Moore AM, Johnson CS, et al. A phase II study of gemcitabine in combination with radiation therapy in patients with localized, unresectable, pancreatic cancer: a Hoosier Oncology Group study. Am J Clin Oncol. 2011;34(5):460-465.
Sahora K, Kuehrer I, Eisenhut A, et al. NeoGemOx: gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer. Surgery. 2011;149(3):311-320.
Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7(4):e1000267.
Talamonti MS, Small W, Jr., Mulcahy MF, et al. A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol. 2006;13(2):150-158.
Huguet F, Girard N, Guerche CS, Hennequin C, Mornex F, Azria D. Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review. J Clin Oncol. 2009;27(13):2269-2277.
Sultana A, Tudur Smith C, Cunningham D, et al. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy. Br J Cancer. 2007;96(8):1183-1190.
Shinchi H, Takao S, Noma H, et al. Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2002;53(1):146-150.
Wolff RA, Evans DB, Gravel DM, et al. Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma. Clin Cancer Res. 2001;7(8):2246-2253.
Chang DT, Schellenberg D, Shen J, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115(3):665-672.
Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008;19(9):1592-1599.
Cohen SJ, Dobelbower R, Jr., Lipsitz S, et al. A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282. Int J Radiat Oncol Biol Phys. 2005;62(5):1345-1350.
Louvet C, Labianca R, Hammel P, et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005;23(15):3509-3516.
Conroy T, Paillot B, Francois E, et al. Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer - a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol. 2005;23(6):1228-1236.
Michelakos T, Pergolini I, Castillo CF, et al. Predictors of resectability and survival in patients with borderline and locally advanced pancreatic cancer who underwent neoadjuvant treatment with FOLFIRINOX. Ann Surg. 2019;269(4):733-740.
Perri G, Prakash L, Qiao W, et al. Response and survival associated with first-line FOLFIRINOX vs. gemcitabine and nab-paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma. JAMA Surg. 2020;155(9):832-839.
Wolfe AR, Prabhakar D, Yildiz VO, et al. Neoadjuvant-modified FOLFIRINOX vs. nab-paclitaxel plus gemcitabine for borderline resectable or locally advanced pancreatic cancer patients who achieved surgical resection. Cancer Med. 2020;9(13):4711-4723.
Rocha Lima CM, Green MR, Rotche R, et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol. 2004;22(18):3776-3783.
Australasian Gastro-intestinal Trials Group. Definition of surgical standards for pancreatic cancer: A consensus statement by the Australasian Gastro-Intestinal Trials Group. Australia. 2015.
Motoi F, Ishida K, Fujishima F, et al. Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial. Ann Surg Oncol. 2013;20(12):3794-3801.
Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. New Engl J Med. 2004;350(12):1200-1210.
Kamarajah SK, Burns WR, Frankel TL, Cho CS, Nathan H. Validation of the American Joint Commission on Cancer (AJCC) 8th edition staging system for patients with pancreatic adenocarcinoma: a Surveillance, Epidemiology and End Results (SEER) analysis. Ann Surg Oncol. 2017;24(7):2023-2030.
Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. New Engl J Med. 2018;379(25):2395-2406.
Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011-1024.
Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. New Engl J Med. 2013;369(18):1691-1703.