Paradigm Shifting of Systemic Chemotherapy for Unresectable Pancreatic Cancer in Japan
Abstract
:1. Introduction
2. Metastatic Pancreatic Cancer
3. Locally Advanced Pancreatic Cancer
4. Hereditary Pancreatic Cancer
5. Second-Line Chemotherapy
6. Future Perspectives of Chemotherapy for Unresectable Pancreatic Cancer
Conflicts of Interest
References
- Hruban, R.H. Pancreatic cancer. In World Cancer Report 2014; World Health Organization: Geneva, Switzerland, 2014; pp. 413–421. [Google Scholar]
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology, Pancreatic adenocarcinoma, Version 3. 2019. Available online: https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf (assessed on 4 August 2019).
- Conroy, T.; Desseigne, F.; Ychou, M.; Bouché, O.; Guimbaud, R.; Bécouarn, Y.; Adenis, A.; Raoul, J.L.; Gourgou-Bourgade, S.; de la Fouchardière, C.; et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 2011, 364, 1817–1825. [Google Scholar] [CrossRef] [PubMed]
- Von Hoff, D.D.; Ervin, T.; Arena, F.P.; Chiorean, E.G.; Infante, J.; Moore, M.; Seay, T.; Tjulandin, S.A.; Ma, W.W.; Saleh, M.N.; et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 2013, 369, 1691–1703. [Google Scholar] [CrossRef] [PubMed]
- Okusaka, T.; Ikeda, M.; Fukutomi, A.; Ioka, T.; Furuse, J.; Ohkawa, S.; Isayama, H.; Boku, N. Phase II study of FOLFIRINOX for metastatic chemotherapy-naïve Japanese pancreatic cancer patients. Cancer Sci. 2014, 105, 1321–1326. [Google Scholar] [CrossRef] [PubMed]
- Mahaseth, H.; Brutcher, E.; Kauh, J.; Hawk, N.; Kim, S.; Chen, Z.; Kooby, D.A.; Maithel, S.K.; Landry, J.; El-Rayes, B.F. Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas 2013, 42, 1311–1315. [Google Scholar] [CrossRef] [PubMed]
- Stein, S.M.; James, E.S.; Deng, Y.; Cong, X.; Kortmansky, J.S.; Li, J.; Staugaard, C.; Indukala, D.; Boustani, A.M.; Patel, V.; et al. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Br. J. Cancer 2016, 114, 737–743. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, X.; Ma, T.; Zhang, Q.; Chen, Y.G.; Guo, C.X.; Shen, Y.N.; Sun, P.W.; Li, G.G.; Gao, S.L.; Que, R.S.; et al. Modified-FOLFIRINOX in metastatic pancreatic cancer: A prospective study in Chinese population. Cancer Lett. 2017, 406, 22–26. [Google Scholar] [CrossRef] [PubMed]
- Ozaka, M.; Ishii, H.; Sato, T.; Ueno, M.; Ikeda, M.; Uesugi, K.; Sata, N.; Miyashita, K.; Mizuno, N.; Tsuji, K.; et al. A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. Cancer Chemother. Pharmacol. 2018, 81, 1017–1023. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, M.; Ueno, H.; Shiba, S.; Hosoi, H.; Ohba, A.; Sakamoto, Y.; Kondo, S.; Morizane, C.; Okusaka, T. Phase I study of S-1, irinotecan plus oxaliplatin combination therapy for advanced pancreatic cancer. Ann. Oncol. 2015, 26 (Suppl. 9), 42–70. [Google Scholar]
- Ueno, H.; Ioka, T.; Ikeda, M.; Ohkawa, S.; Yanagimoto, H.; Boku, N.; Fukutomi, A.; Sugimori, K.; Baba, H.; Yamao, K.; et al. Randomized Phase III Study of Gemcitabine Plus S-1, S-1 Alone, or Gemcitabine Alone in Patients with Locally Advanced and Metastatic Pancreatic Cancer in Japan and Taiwan: GEST Study. J. Clin. Oncol. 2013, 31, 1640–1648. [Google Scholar] [CrossRef]
- Ueno, H.; Ikeda, M.; Ueno, M.; Mizuno, N.; Ioka, T.; Omuro, Y.; Nakajima, T.E.; Furuse, J. Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Cancer Chemother. Pharmacol. 2016, 77, 595–603. [Google Scholar] [CrossRef]
- Hammel, P.; Huguet, F.; van Laethem, J.L.; Goldstein, D.; Glimelius, B.; Artru, P.; Borbath, I.; Bouché, O.; Shannon, J.; André, T.; et al. 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 2016, 315, 1844–1853. [Google Scholar] [CrossRef]
- Ioka, T.; Fukutomi, A.; Mizusawa, J.; Katayama, H.; Nakamura, S.; Ito, Y.; Hiraoka, N.; Ueno, M.; Ikeda, M.; Sugimori, K.; et al. Randomized phase II study of S-1 and concurrent radiotherapy with versus without induction chemotherapy of gemcitabine for locally advanced pancreatic cancer (LAPC): Final analysis of JCOG1106. Ann. Oncol. 2016, 27 (Suppl. 6), 207–242. [Google Scholar] [CrossRef]
- Suker, M.; Beumer, B.R.; Sadot, E.; Marthey, L.; Faris, J.E.; Mellon, E.A.; El-Rayes, B.F.; Wang-Gillam, A.; Lacy, J.; Hosein, P.J.; et al. FOLFIRINOX for locally advanced pancreatic cancer: A systematic review and patient-level meta-analysis. Lancet Oncol. 2016, 17, 801–810. [Google Scholar] [CrossRef]
- Hammel, P.; Lacy, J.; Portales, F. Phase II LAPACT trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC). J. Clin. Oncol. 2008, 36 (Suppl. 4), 204. [Google Scholar] [CrossRef]
- Fukutomi, A.; Mizusawa, J.; Katayama, H.; Okusaka, T.; Ito, T.; Okano, N.; Mizuno, N.; Ikeda, M.; Ueno, M.; Shioji, K. Randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan Clinical Oncology Group Study (JCOG1407). Ann. Oncol. 2017, 28 (Suppl. 5), 263. [Google Scholar] [CrossRef]
- Matsubayashi, H.; Takaori, K.; Morizane, C.; Maguchi, H.; Mizuma, M.; Takahashi, H.; Wada, K.; Hosoi, H.; Yachida, S.; Suzuki, M.; et al. Familial pancreatic cancer: Concept, management and issues. World J. Gastroenterol. 2017, 23, 935–948. [Google Scholar] [CrossRef]
- Fong, P.C.; Boss, D.S.; Yap, T.A.; Tutt, A.; Wu, P.; Mergui-Roelvink, M.; Mortimer, P.; Swaisland, H.; Lau, A.; O’Connor, M.J.; et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 2009, 361, 123–134. [Google Scholar] [CrossRef]
- Taniguchi, T.; Tischkowitz, M.; Ameziane, N.; Hodgson, S.V.; Mathew, C.G.; Joenje, H.; Mok, S.C.; D’Andrea, A.D. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat. Med. 2003, 9, 568–754. [Google Scholar] [CrossRef]
- Fogelman, D.; Sugar, E.A.; Oliver, G.; Shah, N.; Klein, A.; Alewine, C.; Wang, H.; Javle, M.; Shroff, R.; Wolff, R.A.; et al. Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma. Cancer Chemother. Pharmacol. 2015, 76, 489–498. [Google Scholar] [CrossRef] [Green Version]
- Takahashi, H.; Morizane, C.; Nomura, S.; Okano, N.; Tsuda, M.; Mizuno, N.; Satake, H.; Tsuji, K.; Shioji, K.; Ishii, H.; et al. Phase II clinical trial of gemcitabine plus oxaliplatin combination therapy (GEMOX) for the advanced pancreatic adenocarcinoma with a family history of pancreatic/breast/ovarian/prostate cancer or personal history of breast/ovarian/prostate cancer (FABRIC study). Ann. Oncol. 2018, 29 (Suppl. 8), 248–249. [Google Scholar]
- Robson, M.; Im, S.A.; Senkus, E.; Xu, B.; Domchek, S.M.; Masuda, N.; Delaloge, S.; Li, W.; Tung, N.; Armstrong, A.; et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med. 2017, 377, 523–533. [Google Scholar] [CrossRef]
- Moore, K.; Colombo, N.; Scambia, G.; Kim, B.G.; Oaknin, A.; Friedlander, M.; Lisyanskaya, A.; Floquet, A.; Leary, A.; Sonke, G.S.; et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med. 2018, 379, 2495–2505. [Google Scholar] [CrossRef]
- Oza, A.M.; Matulonis, U.A.; Malander, S.; Hudgens, S.; Sehouli, J.; Del Campo, J.M.; Berton-Rigaud, D.; Banerjee, S.; Scambia, G.; Berek, J.S.; et al. Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): Results from a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2018, 19, 1117–1125. [Google Scholar] [CrossRef]
- Lowery, M.A.; Kelsen, D.P.; Capanu, M.; Smith, S.C.; Lee, J.W.; Stadler, Z.K.; Moore, M.J.; Kindler, H.L.; Golan, T.; Segal, A.; et al. Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma. Eur. J. Cancer. 2018, 89, 19–26. [Google Scholar] [CrossRef]
- O’Reilly, E.M.; Lee, J.W.; Lowery, M.A.; Capanu, M.; Stadler, Z.K.; Moore, M.J.; Dhani, N.; Kindler, H.L.; Estrella, H.; Maynard, H.; et al. Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma. Cancer 2018, 124, 1374–1382. [Google Scholar] [CrossRef]
- Golan, T.; Hammel, P.; Reni, M.; Van Cutsem, E.; Macarulla, T.; Hall, M.J.; Park, J.O.; Hochhauser, D.; Arnold, D.; Oh, D.Y. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N. Engl. J. Med. 2019, 381, 317–327. [Google Scholar] [CrossRef]
- Pelzer, U.; Schwaner, I.; Stieler, J.; Adler, M.; Seraphin, J.; Dörken, B.; Riess, H.; Oettle, H. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: A phase III-study from the German CONKO-study group. Eur. J. Cancer 2011, 47, 1676–1681. [Google Scholar] [CrossRef]
- Oettle, H.; Riess, H.; Stieler, J.M.; Heil, G.; Schwaner, I.; Seraphin, J.; Görner, M.; Mölle, M.; Greten, T.F.; Lakner, V.; et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: Outcomes from the CONKO-003 trial. J. Clin. Oncol. 2014, 32, 2423–2429. [Google Scholar] [CrossRef]
- Gill, S.; Ko, Y.-J.; Cripps, C.; Beaudoin, A.; Dhesy-Thind, S.; Zulfiqar, M.; Zalewski, P.; Do, T.; Cano, P.; Lam, W.Y.H.; et al. PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin with or without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy. J. Clin. Oncol. 2016, 34, 3914–3920. [Google Scholar] [CrossRef]
- Ohkawa, S.; Okusaka, T.; Isayama, H.; Fukutomi, A.; Yamaguchi, K.; Ikeda, M.; Funakoshi, A.; Nagase, M.; Hamamoto, Y.; Nakamori, S.; et al. Randomised phase II trial of S-1 plus oxaliplatin vs S-1 in patients with gemcitabine-refractory pancreatic cancer. Br. J. Cancer 2015, 112, 1428–1434. [Google Scholar] [CrossRef]
- Ioka, T.; Komatsu, Y.; Mizuno, N.; Tsuji, A.; Ohkawa, S.; Tanaka, M.; Iguchi, H.; Ishiguro, A.; Kitano, M.; Satoh, T.; et al. Randomised phase II trial of irinotecan plus S-1 in patients with gemcitabine-refractory pancreatic cancer. Br. J. Cancer 2017, 116, 464–471. [Google Scholar] [CrossRef] [Green Version]
- Ioka, T.; Ueno, M.; Ueno, H.; Park, J.O.; Chang, H.M.; Sasahira, N.; Kanai, M.; Chung, I.J.; Ikeda, M.; Nakamori, S.; et al. TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer: A randomised, open-label, phase 3 study (GRAPE trial). Eur. J. Cancer 2019, 106, 78–88. [Google Scholar] [CrossRef]
- Wang-Gillam, A.; Li, C.P.; Bodoky, G.; Dean, A.; Shan, Y.S.; Jameson, G.; Macarulla, T.; Lee, K.H.; Cunningham, D.; Blanc, J.F.; et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): A global, randomised, open-label, phase 3 trial. Lancet 2016, 387, 545–557. [Google Scholar] [CrossRef]
- Ioka, T.; Ueno, M.; Ueno, H.; Kabir, S.; Tokudome, T.; Ikeda, M. A randomized phase 2 study of nanoliposomal irinotecan (nal-IRI, BAX2398)-containing regimen in Japanese patients with metastatic pancreatic adenocarcinoma (mPAC). Ann. Oncol. 2016, 27 (Suppl. 9), 274. [Google Scholar] [CrossRef]
- Satoi, S.; Yamaue, H.; Kato, K.; Takahashi, S.; Hirono, S.; Takeda, S.; Eguchi, H.; Massayuki, S.; Wada, K.; Shinchi, H. Role of adjuvant surgery for patients with initially unresectable pancreatic cancer with a long-term favorable response to non-surgical anti-cancer treatments: Results of a project study for pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J. Hepato Biliary Pancreat. Sci. 2013, 20, 590–600. [Google Scholar]
- Barenboim, A.; Lahat, G.; Geva, R.; Nachmany, I.; Nakache, R.; Goykhman, Y.; Brazowski, E.; Rosen, G.; Isakov, O.; Wolf, I.; et al. Neoadjuvant FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer: An intention to treat analysis. Eur. J. Surg. Oncol. 2018, 44, 1619–1623. [Google Scholar] [CrossRef]
- Yoo, C.; Shin, S.H.; Kim, K.-P.; Jeong, J.H.; Chang, H.-M.; Kang, J.H.; Lee, S.S.; Park, D.H.; Song, T.J.; Seo, D.W.; et al. Clinical outcomes of conversion surgery after neoadjuvant chemotherapy in patients with borderline resectable and locally advanced unresectable pancreatic cancer: A single-center, retrospective analysis. Cancers 2019, 11, 278. [Google Scholar] [CrossRef]
- Royal, R.E.; Levy, C.; Turner, K.; Mathur, A.; Hughes, M.; Kammula, U.S.; Sherry, R.M.; Topalian, S.L.; Yang, J.C.; Lowy, I.; et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J. Immunother. 2010, 33, 828–833. [Google Scholar] [CrossRef]
- Sharma, P.; Dirix, L.; De Vos, F.Y.F.L.; Allison, J.P.; DeCoster, L.; Zaucha, R.; Park, J.O.; VanderWalde, A.M.; Kataria, R.S.; Ferro, S.; et al. Efficacy and tolerability of tremelimumab in patients with metastatic pancreatic ductal adenocarcinoma. J. Clin. Oncol. 2018, 36 (Suppl. 4), 470. [Google Scholar] [CrossRef]
- O’Reilly, E.M.; Oh, D.-Y.; Dhani, N.; Renouf, D.J.; Lee, M.A.; Sun, W.; Fisher, G.A.; Hezel, A.F.; Chang, S.-C.; Vlahovic, G.; et al. A randomized phase 2 study of durvalumab monotherapy and in combination with tremelimumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): ALPS study. J. Clin. Oncol. 2018, 36 (Suppl. 4), 217. [Google Scholar] [CrossRef]
- Wainberg, Z.A.; Hochster, H.S.; Kim, E.J.H.; George, B.; Kalyan, A.; Chiorean, E.G.; Waterhouse, D.M.; Gutierrez, M.; Parikh, A.R.; Jain, R. Phase I study of nivolumab (Nivo)+nab-paclitaxel (nab-P) + gemcitabine (Gem) in advanced pancreatic cancer (APC). J. Clin. Oncol. 2019, 37 (Suppl. 4), 298. [Google Scholar] [CrossRef]
- Postow, M.A.; Callahan, M.K.; Barker, C.A.; Yamada, Y.; Yuan, J.; Kitano, S.; Mu, Z.; Rasalan, T.; Adamow, M.; Ritter, E.; et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N. Engl. J. Med. 2012, 366, 925–931. [Google Scholar] [CrossRef]
Original FOLFIRINOX | Modified FOLFIRINOX | S-IROX | |||||
---|---|---|---|---|---|---|---|
Conroy et al. (2011) [3] | Okusaka et al. (2014) [5] | Mahaseth et al. (2013) [6] | Stein et al. (2016) [7] | Li et al. (2017) [8] | Ozaka et al. (2018) [9] | Shiba et al. (2015) [10] | |
Country | France | Japan | USA | USA | China | Japan | Japan |
N | 171 | 36 | 36 | 37 | 62 | 69 | 18 |
Regimen | |||||||
Irinotecan (mg/m2) | 180 | 180 | 180 | 135 | 135 | 150 | 150 or 165 |
Oxaliplatin (mg/m2) | 85 | 85 | 85 | 85 | 68 | 85 | 85 |
bolus fluorouracil (mg/m2) | 400 | 400 | 0 | 300 | 0 | 0 | - |
continuous infusion fluorouracil (mg/m2) | 2400 | 2400 | 2400 | 2400 | 2400 | 2400 | S-1: 50 or 60 mg, oral, twice daily |
Objective response rate | 31.6% | 38.9% | 25% | 35.1% | 32.5% | 37.7% | 57.1% |
Disease control rate | 70.2% | 69.4% | - | 86.5% | 60% | 78.3% | 92.9% |
Median progression-free survival | 6.4 months | 5.6 months | 8.5 months | 6.1 months | 7.0 months | 5.5 months | - |
Median overall survival | 11.1 months | 10.7 months | 9.0 months | 10.2 months | 10.3 months | 11.2 months | - |
Common toxicities (Grade 3/4) | |||||||
Neutropenia | 45.7% | 77.8% | 3% | 12.2% | 29% | 47.8% | 18% |
Febrile neutropenia | 5.4% | 22.2% | 0 | 4.1% | 0 | 8.7% | - |
Thrombocytopenia | 9.1% | 11.1% | 4% | 9.5% | 4.8% | 2.9% | 12% |
Fatigue | 23.6% | 0% | 13% | 12.2% | 13% | 5.8% | - |
Diarrhea | 12.7% | 8.3% | 13% | 16.2% | 0 | 10.1% | 18% |
Peripheral neuropathy | 9.0% | 5.6% | 4% | 2.7% | 0 | 5.8% | - |
Ueno (2016) [11] | |
---|---|
N | 34 |
Objective response rate | 58.8% |
Disease control rate | 94.1% |
Median PFS | 6.5 months |
Median OS | 13.5 months |
Common toxicities (Grade 3/4) | |
Neutropenia | 70.6% |
Febrile neutropenia | 5.9% |
Thrombocytopenia | 14.7% |
Fatigue | - |
Diarrhea | 5.9% |
Peripheral neuropathy | 11.8% |
Trial | Regimen | n | Response Rate | Median PFS | Median OS | Hazard Ratio (95% CI) | P-value | Author (Year) |
---|---|---|---|---|---|---|---|---|
CONKO-03 | Best supportive care | 23 | NA | NA | 2.3 months | 0.45 | 0.008 | Pelzer (2011) [29] |
OFF | 23 | NA | NA | 4.8 months | (0.24–0.83) | |||
CONKO-03 | FF | 91 | NA | 2.1 months | 3.0 months | NA | 0.014 | Pelzer (2008) [30] |
OFF | 77 | NA | 3.0 months | 6.0 months | ||||
PANCREOX | FF | 54 | 8.5% | 2.9 months | 9.9 months | 1.78 | 0.024 | Gill S (2016) [31] |
FOLOX | 54 | 13.2% | 3.1 months | 6.1 months | (1.08–2.93) | |||
- | S-1 | 135 | 11.5% | 2.8 months | 6.9 months | 1.03 | 0.82 | Ohkawa S (2015) [32] |
SOX | 136 | 20.9% | 3.0 months | 7.4 months | (0.79–1.34) | |||
- | S-1 | 67 | 6.0% | 1.9 months | 5.8 months | 0.75 | 0.13 | Ioka T (2017) [33] |
IRIS | 60 | 8.3% | 3.5 months | 6.8 months | (0.51–1.09) | |||
GRAPE | S-1 | 290 | 19.7% | 2.8 months | 7.9 months | 0.98 | 0.756 | Ioka T (2019) [34] |
TAS118 | 296 | 27.5% | 3.9 months | 7.6 months | (0.82–1.16) | |||
NAPOLI-1 | Fluorouracil/folinic acid/nanoliposomal irinotecan | 117 | 16% | 3.1 months | 6.1 months | 0.67 | 0.012 | Wang-Gillam A (2016) [35] |
Fluorouracil/folinic acid | 119 | 1% | 1.5 months | 4.2 months | (0·49–0·92) | |||
Nanoliposomal irinotecan | 151 | 6% | 2.7 months | 4.9 months | - | - |
© 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Furuse, J. Paradigm Shifting of Systemic Chemotherapy for Unresectable Pancreatic Cancer in Japan. J. Clin. Med. 2019, 8, 1170. https://doi.org/10.3390/jcm8081170
Furuse J. Paradigm Shifting of Systemic Chemotherapy for Unresectable Pancreatic Cancer in Japan. Journal of Clinical Medicine. 2019; 8(8):1170. https://doi.org/10.3390/jcm8081170
Chicago/Turabian StyleFuruse, Junji. 2019. "Paradigm Shifting of Systemic Chemotherapy for Unresectable Pancreatic Cancer in Japan" Journal of Clinical Medicine 8, no. 8: 1170. https://doi.org/10.3390/jcm8081170