advanced and metastatic pancreatic cancer; gemcitabine plus oxaliplatin; second line chemotherapy
Abstract :
[en] Gemcitabine and oxaliplatin (GEMOX) are active as first-line therapy against advanced pancreatic cancer. This study aims to evaluate the activity and tolerability of this combination in patients refractory to standard gemcitabine (GEM). A total of 33 patients (median age of 57) were included with locally advanced and metastatic evaluable diseases, who had progressed during or following GEM therapy. The GEMOX regimen consisted of 1000 mgm(-2) of GEM at a 100-min infusion on day 1, followed on day 2 by 100 mgm(-2) of oxaliplatin at a 2-h infusion; a cycle that was given every 2 weeks. All patients received at least one cycle of GEMOX (median 5; range 1-29). Response by 31 evaluable patients was as follows: PR: 7/31( 22.6%), s.d. >= 8 weeks: 11/31( 35.5%), s.d. < 8 weeks: 1/31( 3.2%), PD: 12/31( 38.7%). Median duration of response and TTP were 4.5 and 4.2 months, respectively. Median survival was 6 months (range 0.5-21). Clinical benefit response was observed in 17/31 patients (54.8%). Grade III/ IV non-neurologic toxicities occurred in 12/33 patients (36.3%), and grade I, II, and III neuropathy in 17(51%), 3(9%), and 4(12%) patients, respectively. GEMOX is a well-tolerated, active regimen that may provide a benefit to patients with advanced pancreatic cancer after progression following standard gemcitabine treatment.
Disciplines :
Oncology
Author, co-author :
Demols, A.
La Marca, Marilèna ; Centre Hospitalier Universitaire de Liège - CHU > Pharmacie
Polus, Marc ; Centre Hospitalier Universitaire de Liège - CHU > Gastro-Entérologie-Hépatologie
Marechal, R.
Gay, F.
Monsaert, E.
Hendlisz, A.
Van Laethem, J. L.
Language :
English
Title :
Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study
Androulakis N, Syrigos K, Polyzos A, Aravantinos G, Stathopoulos GP, Mallas K, Vamvakas L, Georgoulis V (2005) Oxaliplatin for pretreated patients with advanced or metastatic pancreatic cancer: a multicenter phase II study. Cancer Invest 23(1): 9-12
Blaszkowsky LS, Hulke KH, Ryan DP, Clark JW, Meyerhardt J, Zhu AX, Lawrence C, Fuchs CS (2005) A phase II study of erlotinib in combination with capecitabine in previously treated patients with metastatic pancreatic cancer. Proc Am Soc Clin Oncol 2005: abstract 4099
Burris HA, 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: 2403-2413
Faivre S, Raymond E, Woynarowski JM, Cvitkovic E (1999) Supraadditive effect of 2′,2′-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol 44(2): 117-123
Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schonekas H, Rost A, Neuhaus H, Haag C, Stoffregen C, Clemens M (2003) A phase III trial comparing gemcitabine plus cisplatin vs gemcitabine alone in advanced pancreatic carcinoma. Proc Am Soc Clin Oncol 2003 abstract 1003
Louvet C, André T, Lledo G, Hammel P, Bleiberg H, Bouleuc C, Gamelin E, Flesch M, Cvitkovic E, de Gramont A (2002) Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 20(6): 1512-1518
Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, Andre T, Zaniboni A, Ducreux M, Aitini E, Taieb 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): 3509-3516
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht J, Gallinger S, Au K, Ding J, Christy-Bittel J, Parulekar W (2005) Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Proc Am Soc Clin Oncol 2005: abstract 1
Ng M, Norman AR, Cunningham D, Waters J, Oates J, Ross P (2005) Phase II trial evaluating a 2 weekly regimen of irinotecan (IR) and 5-FU/leucovorin (LV) in patients with metastatic pancreatic cancer refractory to chemotherapy. Proc Am Soc Clin Oncol 2005: abstract 4229
Oettle H, Arnold D, Esser M, Huhn D, Riess H (2000) Paclitaxel as weekly second-line therapy in patients with advanced pancreatic carcinoma. Anticancer Drugs 11(8): 635-638
Oettle H, Pelzer U, Stieler J, Hilbig A, Roll L, Schwaner I, Adler M, Detken S, Dörken B, Riess H (2005) Oxaliplatin/folinic acid/5-fluorouracil (24 h) (OFF) plus best supportive care versus best supportive care alone (BSC) in second line therapy of gemcitabine-refractory advanced pancreatic cancer (CONKO 003). Proc Am Soc Clin Oncol 2005: abstract 4031
O'Reilly EM, Abou-Alfa GK, Letourneau R, Harker WG, Modiano M, Hurwitz H, Tchekmedyian NS, Ackerman J, De Jager RL, Eckhardt G (2004) A randomized phase III trial of DX-8951f (exatecan mesylate; DX) and gemcitabine (GEM) vs gemcitabine alone in advanced pancreatic cancer (APC). Proc Am Soc Clin Oncol 2004: abstract 4006
Richards DA, Kindler HL, Oettle H, Ramanathan RK, Van Laethem J-L, Peeters M, Fuchs M, John W, Arning M, Von Hoff D (2004) A randomized phase III study comparing gemcitabine+pemetrexed versus gemcitabine in patients with locally advanced and metastatic pancreas cancer. Proc Am Soc Clin Oncol 2004: abstract 4007
Rocha Lima CMS, Green MR, Rotche R, Miller Jr 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): 3376-3383
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: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 21(18): 3402-3408
Therasse P, Arbuch SG, Eisenhower EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92: 205-216
Tsavaris N, Kosmas C, Skopelitis H, Gouveris P, Kopteridis P, Loukeris D, Sigala F, Zorbala-Sypsa A, Felekouras E, Papalambros E (2005) Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: a phase II study. Invest New Drugs 23(4): 369-375
Ulrich-Pur H, Raderer M, Verena Kornek G, Schull B, Schmid K, Haider K, Kwasny W, Depisch D, Schneeweiss B, Lang F, Scheithauer W (2003) Irinotecan plus ralitrexed vs ralitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer 88(8): 1180-1184
