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Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401

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Abstract

Purpose

Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients.

Methods

A total of 322 patients with metastatic colorectal cancer were randomized to receive biweekly: oxaliplatin 100 mg/m2 i.v. on day 1, capecitabine 1,000 mg/m2 orally twice daily from day 1 to day 11 (OXXEL); or oxaliplatin 85 mg/m2 i.v. on day 1; 6S-leucovorin 250 mg/m2 i.v. and fluorouracil 850 mg/m2 i.v. on day 2 (OXAFAFU).

Results

Eleven complete and 42 partial responses were registered with OXXEL (RR = 34%); six complete and 48 partial responses were obtained with OXAFAFU (RR = 33%) (= 0.999). Severe adverse events were less frequent (32 vs. 43%) with OXXEL, which also reduced the occurrence of severe neutropenia (10 vs. 27%) and febrile neutropenia (6 vs. 13%), but produced more gastric side effects (8 vs. 3%) and diarrhea (13 vs. 8%). QoL did not differ across the two arms. Median PFS was 6.6 months in the OXXEL, and 6.5 months in the OXAFAFU arm (HR = 1.12, P = 0.354). Median overall survival was 16.0 and 17.1 months (HR = 1.01, = 0.883).

Conclusions

OXXEL and OXAFAFU regimens were equally active in metastatic colorectal cancer. The choice should be based on patient preference and on pharmacoeconomic evaluations.

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References

  • Becouarn Y, Ychou M, Ducreux M et al (1998) Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. J Clin Oncol 16:2739–2744

    PubMed  CAS  Google Scholar 

  • Borner MM, Dietrich D, Stupp R et al (2002) Phase II study of capecitabine and oxaliplatin in first- and second-line treatment of advanced or metastatic colorectal cancer. J Clin Oncol 20:1759–1766

    Article  PubMed  CAS  Google Scholar 

  • Cassidy J, Tabernero J, Twelves C et al (2004) XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol 22:2084–2091

    Article  PubMed  CAS  Google Scholar 

  • Cassidy J, Douillard J-Y, Twelves C et al (2006) Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes’ C colon cancer: the X-ACT trial. Br J Cancer 94:1122–1129

    Article  PubMed  CAS  Google Scholar 

  • Cassidy J, Clarke S, Diaz-Rubio E et al. (2007) XELOX vs FOLFOX4: efficacy results from XELOX-1/NO16966, a randomised phase III trial in first-line metastatic colorectal cancer (MCRC). Proc Am Soc Clin Oncol Gastrointestinal Cancer Symposium (abstr 270)

  • Comella P, Massidda B, Filippelli G et al (2005a) Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial. Ann Oncol 16:878–886

    Article  PubMed  CAS  Google Scholar 

  • Comella P, Natale D, Farris A et al (2005b) Capecitabine plus oxaliplatin for the first-line treatment of elderly patients with metastatic colorectal carcinoma. Cancer 104:282–289

    Article  PubMed  CAS  Google Scholar 

  • Comella P, Massidda B, Palmeri S et al (2005c) Biweekly oxaliplatin combined with oral capecitabine (OXXEL regimen) as first-line treatment of metastatic colorectal cancer patients. A Southern Italy Cooperative oncology group phase II study. Cancer Chemother Pharmacol 56:481–486

    Article  PubMed  CAS  Google Scholar 

  • Cox DR (1972) Regression models and life tables. J R Stat Soc 34:187–202

    Google Scholar 

  • Díaz-Rubio E, Sastre J, Zaniboni A et al (1998) Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: a phase II multicentric study. Ann Oncol 9:105–108

    Article  PubMed  Google Scholar 

  • Díaz-Rubio E, Tabernero J, Gómez-Espaňa J et al (2007) Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish cooperative group for the treatment of digestive tumors trial. J Clin Oncol 25:4224–4230

    Article  PubMed  Google Scholar 

  • Ducreux M, Bennouna J, Hebbar M et al. (2007) Efficacy and safety findings from a randomised phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5- FU/LV + O (FOLFOX-6) for metastatic colorectal cancer (MCRC). Proc Am Soc Clin Oncol 170s (abstr 4029)

  • Feliu J, Salud A, Escudero P et al (2006) XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer. Br J Cancer 94:969–975

    Article  PubMed  CAS  Google Scholar 

  • Fischel J-L, Etienne M-C, Formento P, Milano G (1998) Search for the optimal schedule for the oxaliplatin/5-fluorouracil association modulated or not by folinic acid: preclinical data. Clin Cancer Res 4:2529–2535

    PubMed  CAS  Google Scholar 

  • Giacchetti S, Perpoint B, Zidani R et al (2000) Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 18:136–147

    PubMed  CAS  Google Scholar 

  • Goldberg RM, Sargent DJ, Morton RF et al (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22:23–30

    Article  PubMed  CAS  Google Scholar 

  • Goldberg RM, Sargent DJ, Morton RF et al (2006) Randomized controlled trial of reduced-dose bolus fluorouracil plus leucovorin and irinotecan or infused fluorouracil plus leucovorin and oxaliplatin in patients with previously untreated metastatic colorectal cancer: a North American intergroup trial. J Clin Oncol 24:3347–3353

    Article  PubMed  CAS  Google Scholar 

  • de Gramont A, Figer A, Seymour M et al (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947

    PubMed  Google Scholar 

  • Grothey A, Jordan K, Kellner O et al. (2003): Capecitabine plus irinotecan (CAPIRI) vs capecitabine plus oxaliplatin (CAPOX) as first-line therapy of advanced colorectal cancer (ACRC): updated results of a randomized phase II trial. Proc ECCO 12, Eur J Cancer S90 (abstract # 295)

  • Hochster HS, Hart LL, Ramanathan RK et al. (2006) Safety and efficacy of oxaliplatin/fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC): final analysis of the TREE-Study. Proc Am Soc Clin Oncol Annual Meeting 24, 18S (abstract 3510)

  • Kaplan ES, Meier P (1958) Non parametric estimation for incomplete observations. J Am Stat Assoc 53:557–580

    Article  Google Scholar 

  • Lévi F, Misset JL, Brienza S et al (1992) A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer. Cancer 69:893–900

    Article  PubMed  Google Scholar 

  • Liu G, Franssen E, Fitch MI, Warner E (1997) Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 15:110–115

    PubMed  CAS  Google Scholar 

  • Machover D, Díaz-Rubio E, De Gramont A et al (1996) Two consecutive phase II study of oxaliplatin (L-OHP) for the treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines. Ann Oncol 7:95–98

    PubMed  CAS  Google Scholar 

  • Mantel N (1966) Evaluation of survival data and two new ranks of order statistics arising in its considerations. Cancer Chemother Rep 50:163–170

    PubMed  CAS  Google Scholar 

  • Martoni AA, Pinto C, Di Fabio F et al (2006) Capecitabine plus oxaliplatin (XELOX) versus protracted 5-fluorouracil venous infusion plus oxaliplatin (pviFOX) as first-line treatment in advanced colorectal cancer: a GOAM phase II randomised study (FOCA trial). Eur J Cancer 42:3161–3168

    Article  PubMed  CAS  Google Scholar 

  • Mayer RJ (2007) Should capecitabine replace infusional fluorouracil and leucovorin when combined with oxaliplatin in metastatic colorectal cancer? J Clin Oncol 25:4165–4167

    Article  PubMed  CAS  Google Scholar 

  • Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214

    Article  PubMed  CAS  Google Scholar 

  • Osoba D, Rodrigues G, Myles J, Zee B, Pater J (1998) Interpreting the significance of changes in health-related quality-of-Life scores. J Clin Oncol 16:139–144

    PubMed  CAS  Google Scholar 

  • Pfeiffer P, Mortensen JP, Bjerregaard B et al (2006) Patient preference for oral or intravenous chemotherapy: a randomised cross-over trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with colorectal cancer. Eur J Cancer 42:2738–2743

    Article  PubMed  CAS  Google Scholar 

  • Porschen R, Arkenau H-T, Kubicka S et al (2007) Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO colorectal study group. J Clin Oncol 25:4217–4223

    Article  PubMed  CAS  Google Scholar 

  • Raymond E, Chaney SG, Taamma A, Cvitkovic E (1998) Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol 9:1053–1071

    Article  PubMed  CAS  Google Scholar 

  • Salts LB, Clarke S, Diaz-Rubio E et al. (2007) Bevacizumab (Bev) in combination with XELOX or FOLFOX4: efficacy results from XELOX-1/NO16966, a randomized phase III trial in the first-line metastatic colorectal cancer (MCRC). Proc Am Soc Clin Oncol Gastrointestinal Cancer Symposium (abstract 238)

  • Sandomenico C, Filippelli G, Massidda B et al. (2006): Biweekly oxaliplatin plus Xeloda (OXXEL) versus oxaliplatin plus folinic acid-modulated 5-fluorouracil i.v. bolus (OXAFAFU) in metastatic colorectal carcinoma (MCC): safety interim analysis of a Southern Italy Cooperative oncology group (SICOG) phase III trial. Proc Am Soc Clin Oncol 168 s (abstract 3590)

  • Twelves C, Gollins S, Grieve R, Samuel L (2006) A randomised cross-over trial comparing patient preference for oral capecitabine and 5-fluorouracil/leucovorin regimens in patients with advanced colorectal cancer. Ann Oncol 7:239–245

    Google Scholar 

  • Ward SE, Kaltenthaler E, Cowan J et al (2006) The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer. Br J Cancer 95:27–33

    Article  PubMed  CAS  Google Scholar 

  • Zeuli M, Nardoni C, Pino MS et al (2003) Phase II study of capecitabine and oxaliplatin as first-line treatment in advanced colorectal cancer. Ann Oncol 14:1378–1382

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The following investigators of the Southern Italy Cooperative Oncology Group are acknowledged as contributors to this trial: Rossana Casaretti MD, Claudia Sandomenico MD, Department of Medical Oncology, National Tumour Institute, Naples; Silvana Leo MD, Medical Oncology, City Hospital, Lecce; Salvatore Tafuto MD, Medical Oncology, City Hospital, Pozzuoli; Ettore Greco MD, Medical Oncology, City Hospital, Lametia Terme; Mario Roselli PhD, Chair of Medical Oncology, Tor Vergata University Medical School, Rome; Valerio Milia MD, Medical Oncology, City Hospital, Macomer; Antonio Gambardella PhD, Chair of Geriatrics, Second University Medical School, Naples; Sergio Mancarella MD, Medical Oncology, City Hospital, Galatina; Giancarlo Di Pinto MD, Medical Oncology, City Hospital, Castrovillari; Lucio De Luca MD, Medical Oncology, Pellegrini Hospital, Naples; Giacomo Vessia MD, Medical Oncology, City Hospital, Altamura, Italy. This work was partially supported by Italian Ministry of Health (FSN 2004). We thank Luca Franco and Marina Licenziato for their invaluable contribution in the data management.

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Correspondence to Pasquale Comella.

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Comella, P., Massidda, B., Filippelli, G. et al. Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401. J Cancer Res Clin Oncol 135, 217–226 (2009). https://doi.org/10.1007/s00432-008-0454-7

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