This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Falcone, A. Articles by Conte, P. Search for Related Content PubMed PubMed Citation Articles by Falcone, A. Articles by Conte, P. Social Bookmarking                            What's this?

Biweekly Chemotherapy With Oxaliplatin, Irinotecan, Infusional Fluorouracil, and Leucovorin: A Pilot Study in Patients With Metastatic Colorectal Cancer

From the Division of Medical Oncology, Department of Oncology, Civil Hospital, Livorno; Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants, and Advanced Technologies in Medicine, University of Pisa; and Division of Medical Oncology, Department of Oncology, S. Chiara Hospital, Pisa, Italy.

Address reprint requests to Alfredo Falcone, MD, Divisione di Oncologia Medica, Presidio Ospedaliero, V.le Alfieri, 36, 57121 Livorno, Italy; email: a.falcone{at}med.unipi.it

PURPOSE: To determine the feasibility, recommended doses, plasma pharmacokinetics, and antitumor activity of a biweekly chemotherapy regimen with oxaliplatin (L-OHP), irinotecan (CPT-11), infusional fluorouracil (5-FU), and leucovorin (LV) in metastatic colorectal cancer patients.

PATIENTS AND METHODS: Patients received CPT-11 followed by L-OHP and LV 200 mg/m² and followed by 5-FU 3,800 mg/m² as a 48-hour infusion, repeated every 2 weeks. In the first part of the study, an escalation of CPT-11 dose and/or a decrease of the L-OHP dose were planned. Once the recommended doses of CPT-11 and L-OHP were determined, all subsequent patients were treated at the recommended doses.

RESULTS: Forty-two patients entered the study. CPT-11 175 mg/m² and L-OHP 100 mg/m² in combination with LV 200 mg/m² and 5-FU 3,800 mg/m² could be administered with acceptable toxicities; 39 patients were treated at these dose levels. The pharmacokinetics parameters of the agents used and their metabolites did not seem to be influenced by the concomitant use of the other drugs. The most relevant toxicities were diarrhea and neutropenia, with 14% of patients experiencing one episode of febrile neutropenia. In five patients (11.9%) a complete and in 25 (59.5%) a partial response was demonstrated, for an objective response rate of 71.4% (95% confidence interval, 47% to 83%). In 11 patients (26%), a surgical resection of residual disease could be performed. Median progression-free and overall survival times were 10.4 and 26.5 months, respectively.

CONCLUSION: This biweekly regimen is feasible and has acceptable and manageable toxicities and no apparent relevant pharmacokinetics interactions. This combination is associated with a promising antitumor activity, time to progression, and survival. A phase III randomized trial in Italy planned by the Gruppo Oncologico Nord Ovest has just started.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				R. Adam, R. J. de Haas, D. A. Wicherts, T. A. Aloia, V. Delvart, D. Azoulay, H. Bismuth, and D. Castaing Is Hepatic Resection Justified After Chemotherapy in Patients With Colorectal Liver Metastases and Lymph Node Involvement? J. Clin. Oncol., August 1, 2008; 26(22): 3672 - 3680. [Abstract] [Full Text] [PDF]

				E. Bajetta, L. Celio, E. Ferrario, M. Di Bartolomeo, A. Denaro, K. Dotti, M. Mancin, R. Bajetta, A. Colombo, and S. Pusceddu Capecitabine plus oxaliplatin and irinotecan regimen every other week: a phase I/II study in first-line treatment of metastatic colorectal cancer Ann. Onc., November 1, 2007; 18(11): 1810 - 1816. [Abstract] [Full Text] [PDF]

				A. Falcone, S. Ricci, I. Brunetti, E. Pfanner, G. Allegrini, C. Barbara, L. Crino, G. Benedetti, W. Evangelista, L. Fanchini, et al. Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest J. Clin. Oncol., May 1, 2007; 25(13): 1670 - 1676. [Abstract] [Full Text] [PDF]

				A. Ruzzo, F. Graziano, F. Loupakis, E. Rulli, E. Canestrari, D. Santini, V. Catalano, R. Ficarelli, P. Maltese, R. Bisonni, et al. Pharmacogenetic Profiling in Patients With Advanced Colorectal Cancer Treated With First-Line FOLFOX-4 Chemotherapy J. Clin. Oncol., April 1, 2007; 25(10): 1247 - 1254. [Abstract] [Full Text] [PDF]

				J Lee, W. Kang, J. Kwon, S. Oh, H. Lee, H. Kim, B. Park, H. Lim, M. Han, J. Park, et al. Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in patients with untreated metastatic gastric adenocarcinoma Ann. Onc., January 1, 2007; 18(1): 88 - 92. [Abstract] [Full Text] [PDF]

				D. Gholam, S. Giacchetti, C. Brezault-Bonnet, M. Bouchahda, D. Hauteville, R. Adam, B. Ducot, O. Ghemard, F. Kustlinger, C. Jasmin, et al. Chronomodulated Irinotecan, Oxaliplatin, and Leucovorin-Modulated 5-Fluorouracil as Ambulatory Salvage Therapy in Patients with Irinotecan- and Oxaliplatin-Resistant Metastatic Colorectal Cancer Oncologist, November 1, 2006; 11(10): 1072 - 1080. [Abstract] [Full Text] [PDF]

				G. Masi, L. Marcucci, F. Loupakis, E. Cerri, C. Barbara, S. Bursi, G. Allegrini, I. M. Brunetti, R. Murr, S. Ricci, et al. First-line 5-fluorouracil/folinic acid, oxaliplatin and irinotecan (FOLFOXIRI) does not impair the feasibility and the activity of second line treatments in metastatic colorectal cancer Ann. Onc., August 1, 2006; 17(8): 1249 - 1254. [Abstract] [Full Text] [PDF]

				G. Poston, R. Adam, and J.-N. Vauthey Downstaging or Downsizing: Time for a New Staging System in Advanced Colorectal Cancer? J. Clin. Oncol., June 20, 2006; 24(18): 2702 - 2706. [Full Text] [PDF]

				G. Folprecht, A. Grothey, S. Alberts, H.-R. Raab, and C.-H. Kohne Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates Ann. Onc., August 1, 2005; 16(8): 1311 - 1319. [Abstract] [Full Text] [PDF]

				Y. Seium, R. Stupp, T. Ruhstaller, P. Gervaz, G. Mentha, M. Philippe, A. Allal, C. Trembleau, J. Bauer, R. Morant, et al. Oxaliplatin combined with irinotecan and 5-fluorouracil/leucovorin (OCFL) in metastatic colorectal cancer: a phase I-II study Ann. Onc., May 1, 2005; 16(5): 762 - 766. [Abstract] [Full Text] [PDF]

				J. Taieb, P. Artru, F. Paye, C. Louvet, N. Perez, T. Andre, B. Gayet, M. Hebbar, F. M. Goebel, C. Tournigand, et al. Intensive Systemic Chemotherapy Combined With Surgery for Metastatic Colorectal Cancer: Results of a Phase II Study J. Clin. Oncol., January 20, 2005; 23(3): 502 - 509. [Abstract] [Full Text] [PDF]

				G. Masi, G. Allegrini, S. Cupini, L. Marcucci, E. Cerri, I. Brunetti, E. Fontana, S. Ricci, M. Andreuccetti, and A. Falcone First-line treatment of metastatic colorectal cancer with irinotecan, oxaliplatin and 5-fluorouracil/leucovorin (FOLFOXIRI): results of a phase II study with a simplified biweekly schedule Ann. Onc., December 1, 2004; 15(12): 1766 - 1772. [Abstract] [Full Text] [PDF]

				G. J. Griffiths, M. Y. Koh, V. G. Brunton, C. Cawthorne, N. A. Reeves, M. Greaves, M. J. Tilby, D. G. Pearson, C. J. Ottley, P. Workman, et al. Expression of Kinase-defective Mutants of c-Src in Human Metastatic Colon Cancer Cells Decreases Bcl-xL and Increases Oxaliplatin- and Fas-induced Apoptosis J. Biol. Chem., October 29, 2004; 279(44): 46113 - 46121. [Abstract] [Full Text] [PDF]

				C. Pozzo, M. Basso, A. Cassano, M. Quirino, G. Schinzari, N. Trigila, M. Vellone, F. Giuliante, G. Nuzzo, and C. Barone Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-fluorouracil plus folinic acid in colorectal cancer patients Ann. Onc., June 1, 2004; 15(6): 933 - 939. [Abstract] [Full Text] [PDF]

				A. Grothey, D. Sargent, R. M. Goldberg, and H.-J. Schmoll Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment J. Clin. Oncol., April 1, 2004; 22(7): 1209 - 1214. [Abstract] [Full Text] [PDF]

				A. F. Sobrero Scheduling of Fluorouracil: A Forget-Me-Not in the Jungle of Doublets J. Clin. Oncol., January 1, 2004; 22(1): 4 - 6. [Full Text] [PDF]

				E. Odin, Y. Wettergren, S. Nilsson, R. Willen, G. Carlsson, C. P. Spears, L. Larsson, and B. Gustavsson Altered Gene Expression of Folate Enzymes in Adjacent Mucosa Is Associated with Outcome of Colorectal Cancer Patients Clin. Cancer Res., December 1, 2003; 9(16): 6012 - 6019. [Abstract] [Full Text] [PDF]

				R. K. Ramanathan, J. W. Clark, N. E. Kemeny, H.-J. Lenz, K. O. Gococo, D. G. Haller, E. P. Mitchell, and C. G. Kardinal Safety and Toxicity Analysis of Oxaliplatin Combined With Fluorouracil or as a Single Agent in Patients With Previously Treated Advanced Colorectal Cancer J. Clin. Oncol., August 1, 2003; 21(15): 2904 - 2911. [Abstract] [Full Text] [PDF]

				P. Comella, R. Casaretti, V. De Rosa, A. Avallone, F. Izzo, F. Fiore, L. Lapenta, and G. Comella Oxaliplatin plus irinotecan and leucovorin-modulated 5-fluorouracil triplet regimen every other week: a dose-finding study in patients with advanced gastrointestinal malignancies Ann. Onc., December 1, 2002; 13(12): 1874 - 1881. [Abstract] [Full Text] [PDF]