Top

Cancer Chemotherapy and Pharmacology

Published in:

01-03-2015 | Original Article

Retrospective analysis of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) as salvage chemotherapy in patients with gemcitabine-refractory advanced pancreatic cancer: inflammation-based prognostic score predicts survival

Authors: Akiyoshi Kasuga, Naohiro Okano, Daisuke Naruge, Hiroshi Kitamura, Atsuko Takasu, Fumio Nagashima, Junji Furuse

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2015

Abstract

Purpose

The purpose of this study was to assess the efficacy and safety of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) in patients with gemcitabine (GEM)-refractory pancreatic cancer (PC) and to explore independent variables associated with survival.

Methods

We retrospectively reviewed consecutive patients with GEM-refractory PC who received FGS at our institution from March 2009 to December 2013. GEM was administered by fixed dose rate intravenous infusion of 1,200 mg/m² as a 120-min infusion on day 1, and S-1 was administered orally twice a day at a dose of 40 mg/m² on days 1–7. Cycles were repeated every 14 days.

Results

Sixty-one patients with GEM-refractory PC received FGS. Sixteen patients received FGS as third-line treatment. Twenty-nine patients (48 %) had a history of S-1 administration. The objective response rate was 13 %, and the disease control rate was 49 %. The median progression-free survival time was 2.7 months, and the median overall survival time was 6.0 months. Major Grade 3 or 4 adverse events included neutropenia (15 %), diarrhea (3 %), anorexia (2 %), and fatigue (2 %). A high inflammation-based prognostic score (modified Glasgow prognostic score (mGPS), which incorporates C-reactive protein and albumin), a performance status >0, and serum carbohydrate antigen 19–9 level >2,000 IU/ml were independently associated with a poor outcome.

Conclusions

FGS might be effective and well tolerated as salvage chemotherapy in a practical setting. The inflammation-based prognostic score is a simple and reliable indicator of survival in the setting of salvage chemotherapy.

Burris HA III, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15(6):2403–2413PubMed

Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W (2007) 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 25(15):1960–1966. doi:10.1200/jco.2006.07.9525 CrossRefPubMed

Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703. doi:10.1056/NEJMoa1304369 CrossRef

Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M (2013) 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 31(13):1640–1648. doi:10.1200/jco.2012.43.3680 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

Morizane C, Okusaka T, Furuse J, Ishii H, Ueno H, Ikeda M, Nakachi K, Najima M, Ogura T, Suzuki E (2009) A phase II study of S-1 in gemcitabine-refractory metastatic pancreatic cancer. Cancer Chemother Pharmacol 63(2):313–319. doi:10.1007/s00280-008-0741-7 CrossRefPubMed

Morizane C, Okusaka T, Ueno H, Kondo S, Ikeda M, Furuse J, Shinichi O, Nakachi K, Mitsunaga S, Kojima Y, Suzuki E, Ueno M, Yamaguchi T (2012) Phase I/II study of gemcitabine as a fixed dose rate infusion and S-1 combination therapy (FGS) in gemcitabine-refractory pancreatic cancer patients. Cancer Chemother Pharmacol 69(4):957–964. doi:10.1007/s00280-011-1786-6 CrossRefPubMed

Tempero M, Plunkett W, Ruiz Van Haperen V, Hainsworth J, Hochster H, Lenzi R, Abbruzzese J (2003) Randomized phase II comparison of dose-intense gemcitabine: 30-min infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 21(18):3402–3408. doi:10.1200/jco.2003.09.140 CrossRefPubMed

Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, Alberts S, O’Dwyer P, Haller D, Catalano P, Cella D, Benson AB 3rd (2009) Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-min infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 27(23):3778–3785. doi:10.1200/jco.2008.20.9007 CrossRefPubMedCentralPubMed

10.

Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ (2003) Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer 89(6):1028–1030. doi:10.1038/sj.bjc.6601242 CrossRefPubMedCentralPubMed

11.

Proctor MJ, Morrison DS, Talwar D, Balmer SM, O’Reilly DS, Foulis AK, Horgan PG, McMillan DC (2011) An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study. Br J Cancer 104(4):726–734. doi:10.1038/sj.bjc.6606087 CrossRefPubMedCentralPubMed

12.

Pelzer U, Schwaner I, Stieler J, Adler M, Seraphin J, Dorken B, Riess H, Oettle H (2011) 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 47(11):1676–1681. doi:10.1016/j.ejca.2011.04.011 CrossRefPubMed

13.

Sudo K, Yamaguchi T, Nakamura K, Denda T, Hara T, Ishihara T, Yokosuka O (2011) Phase II study of S-1 in patients with gemcitabine-resistant advanced pancreatic cancer. Cancer Chemother Pharmacol 67(2):249–254. doi:10.1007/s00280-010-1311-3 CrossRefPubMed

14.

Todaka A, Fukutomi A, Boku N, Onozawa Y, Hironaka S, Yasui H, Yamazaki K, Taku K, Machida N, Sakamoto T, Tomita H (2010) S-1 monotherapy as second-line treatment for advanced pancreatic cancer after gemcitabine failure. Jpn J Clin Oncol 40(6):567–572. doi:10.1093/jjco/hyq005 CrossRefPubMed

15.

Boeck S, Wilkowski R, Bruns CJ, Issels RD, Schulz C, Moosmann N, Laessig D, Haas M, Golf A, Heinemann V (2007) Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer. Oncology 73(3–4):221–227. doi:10.1159/000127413 CrossRefPubMed

16.

Takahara N, Isayama H, Nakai Y, Sasaki T, Hamada T, Uchino R, Mizuno S, Miyabayashi K, Kogure H, Yamamoto N, Sasahira N, Hirano K, Ijichi H, Tateishi K, Tada M, Koike K (2013) A retrospective study of S-1 and oxaliplatin combination chemotherapy in patients with refractory pancreatic cancer. Cancer Chemother Pharmacol 72(5):985–990. doi:10.1007/s00280-013-2278-7 CrossRefPubMed

17.

Assaf E, Verlinde-Carvalho M, Delbaldo C, Grenier J, Sellam Z, Pouessel D, Bouaita L, Baumgaertner I, Sobhani I, Tayar C, Paul M, Culine S (2011) 5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma. Oncology 80(5–6):301–306. doi:10.1159/000329803 CrossRefPubMed

18.

Lee MG, Lee SH, Lee SJ, Lee YS, Hwang JH, Ryu JK, Kim YT, Kim DU, Woo SM (2013) 5-Fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with advanced pancreatic cancer who have progressed on gemcitabine-based therapy. Chemotherapy 59(4):273–279. doi:10.1159/000356158 CrossRefPubMed

19.

Tanaka T, Ikeda M, Okusaka T, Ueno H, Morizane C, Hagihara A, Iwasa S, Kojima Y (2008) Prognostic factors in Japanese patients with advanced pancreatic cancer treated with single-agent gemcitabine as first-line therapy. Jpn J Clin Oncol 38(11):755–761. doi:10.1093/jjco/hyn098 CrossRefPubMed

20.

Yi JH, Lee J, Park SH, Lee KT, Lee JK, Lee KH, Choi DW, Choi SH, Heo JS, Lim do H, Park YS, Lim HY, Kang WK, Park K, Park JO (2011) A prognostic model to predict clinical outcomes with first-line gemcitabine-based chemotherapy in advanced pancreatic cancer. Oncology 80(3–4):175–180. doi:10.1159/000328449 CrossRefPubMed

21.

Shimoda M, Katoh M, Kita J, Sawada T, Kubota K (2010) The Glasgow prognostic score is a good predictor of treatment outcome in patients with unresectable pancreatic cancer. Chemotherapy 56(6):501–506. doi:10.1159/000321014 CrossRefPubMed

22.

Glen P, Jamieson NB, McMillan DC, Carter R, Imrie CW, McKay CJ (2006) Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology 6(5):450–453. doi:10.1159/000094562 CrossRefPubMed

23.

La Torre M, Nigri G, Cavallini M, Mercantini P, Ziparo V, Ramacciato G (2012) The Glasgow prognostic score as a predictor of survival in patients with potentially resectable pancreatic adenocarcinoma. Ann Surg Oncol 19(9):2917–2923. doi:10.1245/s10434-012-2348-9 CrossRefPubMed

Title: Retrospective analysis of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) as salvage chemotherapy in patients with gemcitabine-refractory advanced pancreatic cancer: inflammation-based prognostic score predicts survival
Authors: Akiyoshi Kasuga
Naohiro Okano
Daisuke Naruge
Hiroshi Kitamura
Atsuko Takasu
Fumio Nagashima
Junji Furuse
Publication date: 01-03-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2665-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2015

Low-dose-intensity bevacizumab with weekly irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer

Population pharmacokinetic analysis of oxaliplatin in adults and children identifies important covariates for dosing

Pharmacokinetics of neamine in rats and anti-cervical cancer activity in vitro and in vivo

Effect of axitinib on the QT interval in healthy volunteers

A randomized phase II study of combination therapy with S-1, oral leucovorin, and oxaliplatin (SOL) and mFOLFOX6 in patients with previously untreated metastatic colorectal cancer

Dosing algorithm revisit for busulfan following IV infusion

Keynote webinar | Spotlight on antibody–drug conjugates in cancer