Clinical and Translational Oncology

, Volume 15, Issue 9, pp 705–711 | Cite as

Panitumumab and irinotecan every 3 weeks is an active and convenient regimen for second-line treatment of patients with wild-type K-RAS metastatic colorectal cancer

  • A. CarratoEmail author
  • A. Gómez
  • P. Escudero
  • M. Chaves
  • F. Rivera
  • E. Marcuello
  • E. González
  • C. Grávalos
  • M. Constenla
  • J. Luis Manzano
  • F. Losa
  • J. Maurel
  • R. Dueñas
  • B. Massuti
  • J. Gallego
  • J. Aparicio
  • A. Antón
  • E. Aranda
Research Article



To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC).


Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m2 of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal.


Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032).


This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC.


Colorectal cancer Epidermal growth factor receptor (EGFR) inhibitors Monoclonal antibodies Prospective trial Topoisomerase I inhibitors 



The authors thank the patients and the medical and nursing staff of all the participating institutions: Also, the authors acknowledge Inmaculada Ruiz de Mena from TTD Data Center and Marta Llorens and Xavier Núñez from TFS Trial Form Support for monitoring, statistics and data management. This research, including data collection, analysis and medical writing services, was funded by Amgen. The authors also thank Dr. Beatriz Gil-Alberdi from HealthCo (Madrid, Spain) for her assistance in the preparation of the manuscript. Supported by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), Madrid, Spain.

Conflict of interest

Alfredo Carrato, consultant or advisory role (Amgen, Merck Serono) and research funding (Amgen). Fernando Rivera, consultant or advisory role (Amgen) and research funding (Amgen). Enrique Aranda, consultant or advisory role (Roche and Merck Serono). All remaining authors have declared no conflict of interest.


  1. 1.
    Folprecht G, Seymour MT, Saltz L et al (2008) Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol 26:1443–1451PubMedCrossRefGoogle Scholar
  2. 2.
    Jonker DJ, O’Callaghan CJ, Karapetis CS et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040–2048PubMedCrossRefGoogle Scholar
  3. 3.
    Van Cutsem E, Peeters M, Siena S et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664PubMedCrossRefGoogle Scholar
  4. 4.
    Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757–1765PubMedCrossRefGoogle Scholar
  5. 5.
    Douillard JY, Siena S, Cassidy J et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28:4697–4705PubMedCrossRefGoogle Scholar
  6. 6.
    Peeters M, Price TJ, Cervantes A et al (2010) Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28:4706–4713PubMedCrossRefGoogle Scholar
  7. 7.
    Tabernero J, Ciardiello F, Rivera F et al (2010) Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study. Ann Oncol 21:1537–1545PubMedCrossRefGoogle Scholar
  8. 8.
    Weiner LM, Belldegrun AS, Crawford J et al (2008) Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies. Clin Cancer Res 14:502–508PubMedCrossRefGoogle Scholar
  9. 9.
    Amado RG, Wolf M, Peeters M et al (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26:1626–1634PubMedCrossRefGoogle Scholar
  10. 10.
    Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345PubMedCrossRefGoogle Scholar
  11. 11.
    Fuchs CS, Moore MR, Harker G et al (2003) Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol 21:807–814PubMedCrossRefGoogle Scholar
  12. 12.
    Haller DG, Rothenberg ML, Wong AO et al (2008) Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single-agent fluoropyrimidine therapy for metastatic colorectal carcinoma. J Clin Oncol 26:4544–4550PubMedCrossRefGoogle Scholar
  13. 13.
    Kim GP, Sargent DJ, Mahoney MR et al (2009) Phase III noninferiority trial comparing irinotecan with oxaliplatin, fluorouracil, and leucovorin in patients with advanced colorectal carcinoma previously treated with fluorouracil: N9841. J Clin Oncol 27:2848–2854PubMedCrossRefGoogle Scholar
  14. 14.
    Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26:2311–2319PubMedCrossRefGoogle Scholar
  15. 15.
    Langer C, Kopit J, Awad M et al (2008) Analysis of K-RAS mutations in patients with metastatic colorectal cancer receiving cetuximab in combination with irinotecan: results from the EPIC trial. In: 33rd European Society of Medical Oncology, StockholmGoogle Scholar
  16. 16.
    Andre T, Blons H, Mabro M et al (2012) Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study. Ann Oncol [Epub ahead of print]Google Scholar
  17. 17.
    Seymour MT, Brown SR, Richman S et al (2011) Panitumumab in combination with irinotecan for chemoresistant advanced colorectal cancer: results of PICCOLO, a large randomised trial with prospective molecular stratification. Eur J Cancer 47(Suppl 1):6007Google Scholar
  18. 18.
    Lacouture ME, Mitchell EP, Piperdi B et al (2010) Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol 28:1351–1357PubMedCrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2012

Authors and Affiliations

  • A. Carrato
    • 1
    Email author
  • A. Gómez
    • 2
  • P. Escudero
    • 3
  • M. Chaves
    • 4
  • F. Rivera
    • 5
  • E. Marcuello
    • 6
  • E. González
    • 7
  • C. Grávalos
    • 8
  • M. Constenla
    • 9
  • J. Luis Manzano
    • 10
  • F. Losa
    • 11
  • J. Maurel
    • 12
  • R. Dueñas
    • 13
  • B. Massuti
    • 14
  • J. Gallego
    • 15
  • J. Aparicio
    • 16
  • A. Antón
    • 17
  • E. Aranda
    • 2
  1. 1.Medical Oncology DepartmentRamón y Cajal University HospitalMadridSpain
  2. 2.Medical Oncology DepartmentReina Sofía HospitalCórdobaSpain
  3. 3.Medical Oncology DepartmentClínico Lozano Blesa University HospitalZaragozaSpain
  4. 4.Medical Oncology DepartmentVirgen del Rocío University HospitalSevillaSpain
  5. 5.Medical Oncology DepartmentMarqués de Valdecilla University HospitalSantanderSpain
  6. 6.Medical Oncology DepartmentSanta Creu i Sant Pau HospitalBarcelonaSpain
  7. 7.Medical Oncology DepartmentVirgen de las Nieves HospitalGranadaSpain
  8. 8.Medical Oncology DepartmentDoce de Octubre University HospitalMadridSpain
  9. 9.Medical Oncology DepartmentPontevedra Hospital ComplexPontevedraSpain
  10. 10.Medical Oncology DepartmentCatalán Oncology Institut, German Trias I Pujol HospitalBadalonaSpain
  11. 11.Medical Oncology DepartmentL′Hospitalet General HospitalBarcelonaSpain
  12. 12.Medical Oncology DepartmentClínic HospitalBarcelonaSpain
  13. 13.Medical Oncology DepartmentJaén Hospital ComplexJaenSpain
  14. 14.Medical Oncology DepartmentAlicante General HospitalAlicanteSpain
  15. 15.Medical Oncology DepartmentElche University General HospitalElcheSpain
  16. 16.Medical Oncology DepartmentLa Fe University HospitalValenciaSpain
  17. 17.Medical Oncology DepartmentMiguel Servet HospitalZaragozaSpain

Personalised recommendations