FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study
The purpose of the present study was to evaluate the activity and the tolerability of the FOLFIRI regimen, administered as second-line chemotherapy in patients with locally advanced or metastatic pancreatic cancer after the failure of a gemcitabine-based regimen.
Patients with locally advanced/metastatic disease who received a first-line chemotherapy (one line only) with gemcitabine ± platinoid (cisplatin, oxaliplatin) and who had measurable disease conform with the RECIST criteria were eligible for the study.
FOLFIRI consists of irinotecan 180 mg/m2 iv on day 1, leucovorin (l-form) 200 mg/m2 iv on day 1 and 2, 5-FU 400 mg/m2 iv bolus on days 1 and 2, and 5-FU 600 mg/m2 iv by ci for 22 h on days 1 and 2, repeated every 2 weeks. The primary end point was the response rate.
Among the 50 enrolled patients, 4 partial responses (PR) (8 %) and 14 stable diseases were observed, for a disease control rate of 18/50 (36 %). Forty-one patients (82 %) have been pretreated with cisplatin/oxaliplatin+gemcitabine as first-line chemotherapy. The median progression-free and overall survivals were 3.2 and 5 months, respectively. The 6-month survival rate was 32 %. Grade 3–4 neutropenia and diarrhea occurred in 10 (20 %) and 6 (12 %) patients, respectively.
The FOLFIRI regimen showed a modest clinical activity in this quite heavily pretreated patients’ population with locally advanced or metastatic pancreatic cancer with a manageable toxicity profile.
KeywordsPancreatic cancer FOLFIRI Chemotherapy Second-line Irinotecan
The authors thank the staff of the Giscad Foundation Executive Office, Silvia Rota and Luciano Frontini, for data management and secretarial activities. The study is sponsored by Fondazione GISCAD who provided the economical support for insurance and costs related to data management, statistical analysis, and the other activities of central and group coordinating centres. Hospira-Italia srl supports the study providing and managing the drug (Irinotecan) required for the treatment.
Conflict of interest
- 2.Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolò M, Ciaparrone M, Cavanna L, Giuliani F, Maiello E, Testa A, Pederzoli P, Falconi M, Gallo C, Di Maio M, Perrone F; Gruppo Oncologico Italia Meridionale (GOIM), Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente (GISCAD), Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC) (2010) Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol 28:1645–1651Google Scholar
- 3.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, GERCOR, GISCAD (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 23:3509–3516PubMedCrossRefGoogle Scholar
- 4.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, National Cancer Institute of Canada Clinical Trials Group (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 25:1960–1966Google Scholar
- 5.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 27:5513–5518PubMedCrossRefGoogle Scholar
- 6.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, Groupe Tumeurs Digestives of Unicancer, PRODIGE Intergroup (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825Google Scholar
- 9.Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247PubMedCrossRefGoogle Scholar
- 11.Kaplan EL, Meier P (1961) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481Google Scholar
- 14.Gebbia V, Maiello E, Giuliani F, Borsellino N, Arcara C, Colucci G (2010) Irinotecan plus bolus/infusional 5-fluorouracil and leucovorin in patients with pretreated advanced pancreatic carcinoma: a multicenter experience of the Gruppo Oncologico Italia Meridionale. Am J Clin Oncol 33:461–464PubMedCrossRefGoogle Scholar
- 15.Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, Lee SS, Seo DW, Lee SK, Kim MH, Han DJ, Kim SC, Lee JL (2009) A randomised phase II study of modified FOLFIRI.3 versus modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer 101:1658–1663PubMedCrossRefGoogle Scholar
- 16.Taïeb J, Lecomte T, Aparicio T, Asnacios A, Mansourbakht T, Artru P, Fallik D, Spano JP, Landi B, Lledo G, Desrame J (2007) FOLFIRI.3, a new regimen combining 5-fluorouracil, folinic acid and irinotecan, for advanced pancreatic cancer: results of an Association des Gastro-Enterologues Oncologues (Gastroenterologist Oncologist Association) multicenter phase II study. Ann Oncol 18:498–503PubMedCrossRefGoogle Scholar
- 18.Neuzillet C, Hentic O, Rousseau B, Rebours V, Bengrine Lefèvre L, Raymond E, Ruszniewski P, Louvet C, Hammel P (2011) FOLFIRI regimen as second-/third-line chemotherapy in patients with advanced pancreatic adenocarcinoma refractory to gemcitabine and platinum salts: a retrospective series of 70 patients. J Clin Oncol 29 (suppl 4 abstract):272Google Scholar
- 19.Pelzer U, Schwaner I, Stieler J, Adler M, Seraphin J, Dörken 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 47:1676–1681Google Scholar
- 21.Hosein PJ, de Lima Lopes G Jr, Pastorini VH, Gomez C, Macintyre J, Zayas G, Reis I, Montero AJ, Merchan JR, Rocha Lima CM (2012) A phase II trial of nab-paclitaxel as second-line therapy in patients with advanced pancreatic cancer. Am J Clin Oncol Feb 2. (Epub ahead of print)Google Scholar
- 22.Dimou AT, Syrigos KN, Saif MW (2011) Novel agents in the management of pancreatic adenocarcinoma: phase I studies. Highlights from the “2011 ASCO Gastrointestinal Cancers Symposium”. San Francisco, CA, USA. January 20–22, 2011. JOP 12:114–116Google Scholar
- 23.National Cancer Institute, National Institutes of Health, US Department of Health and Human Services (2010) COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE), ver 4.03, June 2010. (URL: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf)