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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Sudarshana Datta, MD [2]

## Overview

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In patients with pancreatic cancer, surgery is the primary modality of treatment. However, surgery is performed only in a small fraction of patients who have resectable lesions. Majority of patients have unresectable disease and are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy. Curative resection is not performed in cases of extrapancreatic involvement that require palliative therapy. As per the guidelines of The National Comprehensive Cancer Network (NCCN), patients with locally advanced unresectable or metastatic disease should be treated with a combination of Leucovorin, 5-fuorouracil, Oxaliplatin, and Irinotecan also known as FOLFIRINOX regimen. Neoadjuvant therapy is preferred as shrinkage of the tumor using chemotherapy makes resection easier and improves patient prognosis. Radiotherapy may also form part of neoadjuvant therapy to facilitate tumor shrinkage, but its use on unresectable tumors remains controversial.

## Medical Therapy

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* In patients with pancreatic cancer, surgery is the primary modality of treatment.
* Patients with unresectable disease are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy.
* Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients.
* The different types of treatment modalities available for patients with pancreatic cancer are:
* Surgery
* Radiation therapy
* Chemotherapy
* Chemoradiation therapy
* Targeted therapy

* New types of treatment such as biologic therapy, are being studied in clinical trials.

### Chemotherapy guidelines

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* The National Comprehensive Cancer Network (NCCN) has recommended guidelines for treatment in patients based on their performance status.
* In order to predict survival of patients in various stages of pancreatic cancer, the performance status of a patient is a major prognostic factor.
* Patients with poor prognostic factors have poor performance status. This includes:[1]
* Metastatic disease
* Large tumor
* Severe weight loss
* Preferred regimens based on performance status in locally advanced/metastatic disease are enlisted in the table as follows:[2][3][4][5][6][7][8][9][10][11][12][13][14]

PREFERRED REGIMENS BASED ON PERFORMANCE STATUS IN LOCALLY ADVANCED/METASTATIC DISEASE

Good perfomance status  | FOLFIRINOX[15][16][17][18][19][20][21][22][23]
Good perfomance status with intolerance to FOLFIRINOX | Paclitaxel protein bound AND Gemcitabine
Poor performance status  | Gemcitabine monotherapy[24][25][26][27]
Poor performance status refractory to Gemcitabine | Capecitabine OR capecitabine AND erlotinib[28]

### Preferred regimens based on the stage of pancreatic cancer:

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Stages I-II:

Neoadjuvant therapy :

* There are no standard regimens currently for neoadjuvant treatment of resectable pancreatic cancer.
* Preferred neoadjuvant drug regimens are as follows:
* Capecitabine
* Fluorouracil
* Fluorouracil or Cisplatin plus radiation
* Gemcitabine or Gemcitabine or Cisplatin

Adjuvant chemotherapy:

* In patients with resectable pancreatic cancer:
* Preferred regimen: Gemcitabine 1000 mg/m 2 IV q30min for 3 weeks; every 4 weeks for six cycles

Adjuvant chemotherapy and chemoradiation:

Preferred regimen (1): Gemcitabine 1000 mg/m 2 IV q30min weekly for 3 weeks

Preferred regimen (2): 5-fluorouracil (FU) 250 mg/m 2/day continuous IV infusion via pump

Preferred regimen (3): Radiotherapy 1.8 Gy/day upto a total of 50.4 Gy; then 3-5 wk after chemoradiation: Gemcitabine 1000 mg/m 2 IV q30 min weekly; every 4 weeks for three cycles

#### Stage III:

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Neoadjuvant therapy:

Preferred regimen (1): Gemcitabine 1000 mg/m 2 IV q30 min weekly for 3 weeks, every 4 weeks

Preferred regimen (2): 5-fluorouracil (FU) 500 mg/m 2/day IV bolus on days 1-3 and 29-31 with radiotherapy, 40 Gy

Stage IV:

* Preferred regimen (1): Protein bound Paclitaxel 125 mg/m 2 AND Gemcitabine 1000 mg/m 2 IV over 30-40 min on days 1, 8, and 15 q4weeks
* Preferred regimen (2): Gemcitabine 1000 mg/m 2 IV over 30 min q1week for 7 wk, followed by 1 week off, then weekly for 3 wk
* Preferred regimen (3): Gemcitabine 1000 mg/m 2 IV over 30 min on days 1 and 15 AND Cisplatin 50 mg/m 2 IV over 1 h on days 1 and 15, q4 weeks
* Preferred regimen (3): Gemcitabine 1000 mg/m 2 IV weekly for 7 wk AND Erlotinib 100 mg PO daily on days 1-56 then Gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 plus Erlotinib 100 mg PO q24h on days 1-28 in four cycles
* Preferred regimen (4): Gemcitabine 1000 mg/m 2 IV weekly for 3 weeks q4weeks AND Capecitabine 1660 mg/m 2/day weekly for 3 wk; q4weeks
* Preferred regimen (5): Oxaliplatin 85 mg/m 2 IV AND Irinotecan 180 mg/m 2 IV on day 1 AND Leucovorin 400 mg/m 2 IV on day 1, followed by 5-fluorouracil (FU) 400 mg/m 2 IV bolus on day 1 and then 2400 mg/m 2 IV infusion over 46 h on days 1 and 15

Alternative treatment recommendations for Stage IV:

* Alternative regimen (1): Capecitabine 1250 mg/m 2 PO q12h for 2 weeks, every 3 weeks
* Alternative regimen (2): Capecitabine 1000 mg/m 2 PO q12h for 2 weeks; every 3 weeks AND Erlotinib 150 mg PO daily
* Alternative regimen (3): Irinotecan liposomal 70 mg/m 2 IV infused over 1.5h AND Leucovorin 400 mg/m 2 IV infused over 30min ,followed by 5-fluorouracil (FU) 2400 mg/m 2 IV infused over 46 h q3 weeks
* Alternative regimen (4): 5-fluorouracil (FU) 2000 mg/m 2 IV continuous on days 1, 8, 15, and 22 AND Leucovorin 200 mg/m 2 IV over .5h on days 1, 8, 15, and 22 AND Oxaliplatin 85 mg/m 2 IV on days 8 and 22; q42d

Comparison of one year survival of various regimens is depicted in the table below:

ONE YEAR SURVIVAL OF DIFFERENT REGIMENS

One year survival of FOLFIRINOX (leucovorin AND 5-fluorouracil [LV5-FU] AND oxaliplatin AND Irinotecan) is better than Gemcitabine[16][29][30][31][32][33][34]
One year survival of Gemcitabine AND Erlotinib is better than Gemcitabine[13][35][36]
One year survival of Gemcitabine AND Capecitabine is better than or equal to Gemcitabine [2][37][38][39][40]
One year survival of Gemcitabine AND nanoparticle albumin-bound (nab)-Paclitaxel is better than Gemcitabine[41][42]

### Radiation Therapy

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* The role of radiotherapy as an auxiliary (adjuvant) treatment after potentially curative surgery is controversial.[43][44][45]
* Radiotherapy may form part of neoadjuvant therapy to attempt to shrink a tumor to a resectable state, but its use on unresectable tumors remains controversial.[19][46]

### Palliative Therapy

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Palliative therapy in patients with pancreatic cancer mainly involves the management of symptoms arising as a result of complications of therapy:[47][48][49][50][51][52]

* Pain:
* There are various techniques for pain management as palliative therapy in patients with advanced stage of pancreatic cancer:
* Narcotic analgesics
* Narcotic analgesics AND tricyclic antidepressants or antiemetics
* Radiation therapy

### Adjuvant and Neoadjuvant therapy

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* The use of gemcitabine as adjuvant therapy is considered a standard form of therapy following surgical resection in pancreatic cancer patients.[39][44][53][54][55][56][57][58][59][60]

* Neoadjuvant therapy may be used as a form of therapy due to the following reasons:[4][19][61][62][63][64][65][66][67][68]
* Toxic effects of chemotherapy can be tolerated more easily before surgery as compared to after resection.
* Shrinkage of tumor with neoadjuvant therapy makes resection easier and improves patient prognosis.
* Systemic treatment for cancer involving various systems improves prognosis.
* No therapy is considered as first line therapy under this category.
* Decisions for treatment are made on an individual basis.

### New Treatments

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* Irinotecan in an encapsulated form inside a nanoliposome is being used in advanced pancreatic cancer patients who have earlier been treated using gemcitabine-based chemotherapy.[69]
* Liposomal Irinotecan is used along with leucovorin and fluorouracil.[70]

### Early-Onset Pancreatic Cancer

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* Current treatment guidelines do not differ between early onset pancreatic cancer and later-onset pancreatic cancer.
* Due to a higher frequency of germline DNA damage repair variants and actionable somatic alterations in early-onset pancreatic cancer, targeted therapies such as polyadenosine diphosphate ribose polymerase inhibitors may be used. Those treated with targeted therapies had significantly longer over all survival compared with those not receiving targeted therapies.[71]
* All patients with early onset pancreatic cancer should undergo germline and somatic genetic sequencing to detect hererditary syndromes and identify therapeutic options.[71]

## References

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1. ↑ Tas F, Sen F, Odabas H, Kılıc L, Keskın S, Yıldız I (2013). "Performance status of patients is the major prognostic factor at all stages of pancreatic cancer". Int. J. Clin. Oncol. 18 (5): 839–46. doi:10.1007/s10147-012-0474-9. PMID 22996141.
2. ↑ 2.0 2.1 Mukherjee S, Hurt CN, Bridgewater J, Falk S, Cummins S, Wasan H, Crosby T, Jephcott C, Roy R, Radhakrishna G, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T (2013). "Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial". Lancet Oncol. 14 (4): 317–26. doi:10.1016/S1470-2045(13)70021-4. PMC 3620899. PMID 23474363.
3. ↑ Hurt CN, Falk S, Crosby T, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T, Mukherjee S (2017). "Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer". Br. J. Cancer. 116 (10): 1264–1270. doi:10.1038/bjc.2017.95. PMC 5482737. PMID 28376080.
4. ↑ 4.0 4.1 Huguet F, Girard N, Guerche CS, Hennequin C, Mornex F, Azria D (2009). "Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review". J. Clin. Oncol. 27 (13): 2269–77. doi:10.1200/JCO.2008.19.7921. PMID 19307501.
5. ↑ Hazel JJ, Thirlwell MP, Huggins M, Maksymiuk A, MacFarlane JK (1981). "Multi-drug chemotherapy with and without radiation for carcinoma of the stomach and pancreas: a prospective randomized trial". J Can Assoc Radiol. 32 (3): 164–5. PMID 7028759.
6. ↑ Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouché O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L (2008). "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. 19 (9): 1592–9. doi:10.1093/annonc/mdn281. PMID 18467316.
7. ↑ Irigoyen A, Gallego J, Guillén Ponce C, Vera R, Iranzo V, Ales I, Arévalo S, Pisa A, Martín M, Salud A, Falcó E, Sáenz A, Manzano Mozo JL, Pulido G, Martínez Galán J, Pazo-Cid R, Rivera F, García García T, Serra O, Fernández Parra EM, Hurtado A, Gómez Reina MJ, López Gomez LJ, Martínez Ortega E, Benavides M, Aranda E (2017). "Gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group". Eur. J. Cancer. 75: 73–82. doi:10.1016/j.ejca.2016.12.032. PMID 28222309.
8. ↑ Brasiūniene B, Juozaityte E (2007). "The effect of combined treatment methods on survival and toxicity in patients with pancreatic cancer". Medicina (Kaunas). 43 (9): 716–25. PMID 17986845.
9. ↑ Middleton G, Palmer DH, Greenhalf W, Ghaneh P, Jackson R, Cox T, Evans A, Shaw VE, Wadsley J, Valle JW, Propper D, Wasan H, Falk S, Cunningham D, Coxon F, Ross P, Madhusudan S, Wadd N, Corrie P, Hickish T, Costello E, Campbell F, Rawcliffe C, Neoptolemos JP (2017). "Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial". Lancet Oncol. 18 (4): 486–499. doi:10.1016/S1470-2045(17)30084-0. PMID 28259610.
10. ↑ Xia BT, Fu B, Wang J, Kim Y, Ahmad SA, Dhar VK, Levinsky NC, Hanseman DJ, Habib DA, Wilson GC, Smith M, Olowokure OO, Kharofa J, Al Humaidi AH, Choe KA, Abbott DE, Ahmad SA (2017). "Does radiologic response correlate to pathologic response in patients undergoing neoadjuvant therapy for borderline resectable pancreatic malignancy?". J Surg Oncol. 115 (4): 376–383. doi:10.1002/jso.24538. PMID 28105634.
11. ↑ Choi SJ, Kim HJ, Kim JS, Bak YT, Kim JS (2016). "Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report". BMC Cancer. 16: 588. doi:10.1186/s12885-016-2616-3. PMC 4971692. PMID 27484349.
12. ↑ Wang Y, Hu GF, Zhang QQ, Tang N, Guo J, Liu LY, Han X, Wang X, Wang ZH (2016). "Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis". Drug Des Devel Ther. 10: 1961–72. doi:10.2147/DDDT.S105442. PMC 4912328. PMID 27358556.
13. ↑ 13.0 13.1 Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C (2016). "Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial". JAMA. 315 (17): 1844–53. doi:10.1001/jama.2016.4324. PMID 27139057.
14. ↑ Chen J, Kaley K, Garcon MC, Rodriguez T, Saif MW (2016). "A novel schedule of erlotinib/capecitabine (7/7) as salvage therapy in previously treated advanced pancreatic adenocarcinoma: a case series". Therap Adv Gastroenterol. 9 (2): 162–8. doi:10.1177/1756283X15622779. PMC 4749861. PMID 26929778.
15. ↑ Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé 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): 1817–25. doi:10.1056/NEJMoa1011923. PMID 21561347.
16. ↑ 16.0 16.1 Peddi PF, Lubner S, McWilliams R, Tan BR, Picus J, Sorscher SM, Suresh R, Lockhart AC, Wang J, Menias C, Gao F, Linehan D, Wang-Gillam A (2012). "Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma". JOP. 13 (5): 497–501. PMID 22964956.
17. ↑ Marthey L, Sa-Cunha A, Blanc JF, Gauthier M, Cueff A, Francois E, Trouilloud I, Malka D, Bachet JB, Coriat R, Terrebonne E, De La Fouchardière C, Manfredi S, Solub D, Lécaille C, Thirot Bidault A, Carbonnel F, Taieb J (2015). "FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort". Ann. Surg. Oncol. 22 (1): 295–301. doi:10.1245/s10434-014-3898-9. PMID 25037971.
18. ↑ Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, Wuthrick E, Williams TM, Reardon J, Ellison EC, Bloomston M, Bekaii-Saab T (2015). "Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas". Ann. Surg. Oncol. 22 (4): 1153–9. doi:10.1245/s10434-014-4225-1. PMC 4373613. PMID 25358667.
19. ↑ 19.0 19.1 19.2 Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernández-del Castillo C (2015). "Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer". Ann. Surg. 261 (1): 12–7. doi:10.1097/SLA.0000000000000867. PMC 4349683. PMID 25599322.
20. ↑ Mellon EA, Hoffe SE, Springett GM, Frakes JM, Strom TJ, Hodul PJ, Malafa MP, Chuong MD, Shridhar R (2015). "Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma". Acta Oncol. 54 (7): 979–85. doi:10.3109/0284186X.2015.1004367. PMID 25734581.
21. ↑ Sadot E, Doussot A, O'Reilly EM, Lowery MA, Goodman KA, Do RK, Tang LH, Gönen M, D'Angelica MI, DeMatteo RP, Kingham TP, Jarnagin WR, Allen PJ (2015). "FOLFIRINOX Induction Therapy for Stage 3 Pancreatic Adenocarcinoma". Ann. Surg. Oncol. 22 (11): 3512–21. doi:10.1245/s10434-015-4647-4. PMC 4849545. PMID 26065868.
22. ↑ Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, Staugaard C, Indukala D, Boustani AM, Patel V, Cha CH, Salem RR, Chang B, Hochster HS, Lacy J (2016). "Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer". Br. J. Cancer. 114 (7): 737–43. doi:10.1038/bjc.2016.45. PMC 4984865. PMID 27022826.
23. ↑ Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, El-Rayes BF, Wang-Gillam A, Lacy J, Hosein PJ, Moorcraft SY, Conroy T, Hohla F, Allen P, Taieb J, Hong TS, Shridhar R, Chau I, van Eijck CH, Koerkamp BG (2016). "FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis". Lancet Oncol. 17 (6): 801–810. doi:10.1016/S1470-2045(16)00172-8. PMC 5527756. PMID 27160474.
24. ↑ Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A (2005). "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. 23 (15): 3509–16. doi:10.1200/JCO.2005.06.023. PMID 15908661.
25. ↑ Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D (2004). "Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer". J. Clin. Oncol. 22 (8): 1430–8. doi:10.1200/JCO.2004.10.112. PMID 15084616.
26. ↑ Rocha Lima CM, Green MR, Rotche R, Miller WH, Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL (2004). "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. 22 (18): 3776–83. doi:10.1200/JCO.2004.12.082. PMID 15365074.
27. ↑ Ishii H, Furuse J, Boku N, Okusaka T, Ikeda M, Ohkawa S, Fukutomi A, Hamamoto Y, Nakamura K, Fukuda H (2010). "Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG0506". Jpn. J. Clin. Oncol. 40 (6): 573–9. doi:10.1093/jjco/hyq011. PMID 20185458.
28. ↑ Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS (2007). "Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer". J. Clin. Oncol. 25 (30): 4787–92. doi:10.1200/JCO.2007.11.8521. PMID 17947726.
29. ↑ Conroy T, Gavoille C, Samalin E, Ychou M, Ducreux M (2013). "The role of the FOLFIRINOX regimen for advanced pancreatic cancer". Curr Oncol Rep. 15 (2): 182–9. doi:10.1007/s11912-012-0290-4. PMID 23341367.
30. ↑ Boone BA, Steve J, Krasinskas AM, Zureikat AH, Lembersky BC, Gibson MK, Stoller RG, Zeh HJ, Bahary N (2013). "Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer". J Surg Oncol. 108 (4): 236–41. doi:10.1002/jso.23392. PMC 3816713. PMID 23955427.
31. ↑ Conroy T, Paillot B, François E, Bugat R, Jacob JH, Stein U, Nasca S, Metges JP, Rixe O, Michel P, Magherini E, Hua A, Deplanque G (2005). "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. 23 (6): 1228–36. doi:10.1200/JCO.2005.06.050. PMID 15718320.
32. ↑ Shinchi H, Takao S, Noma H, Matsuo Y, Mataki Y, Mori S, Aikou T (2002). "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. 53 (1): 146–50. PMID 12007953.
33. ↑ "A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. The Gastrointestinal Tumor Study Group". Ann. Surg. 189 (2): 205–8. 1979. PMC 1397020. PMID 426553.
34. ↑ Faris JE, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, Ferrone CR, Wargo JA, Allen JN, Dias LE, Kwak EL, Lillemoe KD, Thayer SP, Murphy JE, Zhu AX, Sahani DV, Wo JY, Clark JW, Fernandez-del Castillo C, Ryan DP, Hong TS (2013). "FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience". Oncologist. 18 (5): 543–8. doi:10.1634/theoncologist.2012-0435. PMC 3662845. PMID 23657686.
35. ↑ Furuse J, Gemma A, Ichikawa W, Okusaka T, Seki A, Ishii T (2017). "Postmarketing surveillance study of erlotinib plus gemcitabine for pancreatic cancer in Japan: POLARIS final analysis". Jpn. J. Clin. Oncol. 47 (9): 832–839. doi:10.1093/jjco/hyx075. PMID 28541474.
36. ↑ Fountzilas C, Chhatrala R, Khushalani N, Tan W, LeVea C, Hutson A, Tucker C, Ma WW, Warren G, Boland P, Iyer R (2017). "A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent". Cancer Chemother. Pharmacol. doi:10.1007/s00280-017-3375-9. PMID 28702772.
37. ↑ Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R (2008). "Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001". J. Clin. Oncol. 26 (22): 3695–701. doi:10.1200/JCO.2007.15.6240. PMID 18669454.
38. ↑ Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP (2009). "Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer". J. Clin. Oncol. 27 (33): 5513–8. doi:10.1200/JCO.2009.24.2446. PMID 19858379.
39. ↑ 39.0 39.1 Sahora K, Kuehrer I, Eisenhut A, Akan B, Koellblinger C, Goetzinger P, Teleky B, Jakesz R, Peck-Radosavljevic M, Ba'ssalamah A, Zielinski C, Gnant M (2011). "NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer". Surgery. 149 (3): 311–20. doi:10.1016/j.surg.2010.07.048. PMID 20817204.
40. ↑ Stokes JB, Nolan NJ, Stelow EB, Walters DM, Weiss GR, de Lange EE, Rich TA, Adams RB, Bauer TW (2011). "Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer". Ann. Surg. Oncol. 18 (3): 619–27. doi:10.1245/s10434-010-1456-7. PMID 21213060.
41. ↑ Passero FC, Saif MW (2017). "Second line treatment options for pancreatic cancer". Expert Opin Pharmacother. 18 (15): 1607–1617. doi:10.1080/14656566.2017.1369955. PMID 28820270.
42. ↑ Saif MW (2014). "Advanced stage pancreatic cancer: novel therapeutic options". Expert Rev Clin Pharmacol. 7 (4): 487–98. doi:10.1586/17512433.2014.910451. PMID 24939470.
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