Abstract
Although the number of elderly patients is increasing each year, this population has
been under-represented in clinical trials. At the same time, the survival of patients
with metastatic colorectal cancer has been improving, not only because of improvements
in chemotherapy, but especially because of the addition of monoclonal antibodies (bevacizumab,
cetuximab and panitumumab). Therefore, it is necessary to define the role of these
new drugs in the elderly population, a group that is heterogeneous and consists of
those who are fit and able to tolerate all therapies equally as well as younger patients
and unfit individuals who should only given best supportive care or therapies specifically
modulated for them. Today, although data from phase II–III studies have helped to
establish the role of bevacizumab in the elderly, few trials have studied anti-epidermal
growth factor receptor (EGFR) antibodies in the same population. This review presents
the results of studies carried out with anti-EGFR agents, with a hope that more trials
will be carried out with these drugs in the elderly in the future.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Geriatric OncologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Colorectal cancer statistics, 2014.CA Cancer J Clin. 2014; 64: 104-117
- Socioeconomic status and changing inequalities in colorectal cancer? A review of the associations with risk, treatment and outcome.Eur J Cancer. 2010; 46: 2681-2695
- Increasing prevalence of comorbidity in patients with colorectal cancer in the south of The Netherlands 1995-2010.Int J Cancer. 2013; 132: 2157-2163
- Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013.Ann Oncol. 2015; 26: 463-476
- Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156
- Frailty in relation to the accumulation of deficits.J Gerontol A Biol Sci Med Sci. 2007; 62: 722-727
- Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used first line.J Clin Oncol. 2005; 23: 9441-9442
- Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.N Engl J Med. 2004; 350: 2335-2342
- Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status.J Clin Oncol. 2011; 29: 2011-2019
- Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer.Ann Oncol. 2014; 25: 1346-1355
- For the AVEX study investigators. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial.Lancet Oncol. 2013; 14: 1077-1085
- Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies.J Cancer Res Clin Oncol. 2010; 136: 737-743
- Natural killer (NK): dendritic cell (DC) cross talk induced by therapeutic monoclonal antibody triggers tumor antigen-specific T cell immunity.Immunol Res. 2011; 50: 248-254
- First-line single-agent cetuximab in elderly patients with metastatic colorectal cancer. A phase II clinical and molecular study of the Spanish group for digestive tumor therapy (TTD).Crit Rev Oncol Hematol. 2011; 77: 78-84
- First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD group study.Oncologist. 2012; 17: 339-345
- Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study.Ann Oncol. 2010; 21: 781-786
- MRC COIN trial investigators. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial.Lancet. 2011; 377: 2103-2114
- Capecitabine as first-line treatment for patients older than 70 years with metastatic colorectal cancer: an Oncopaz Cooperative Group study.J Clin Oncol. 2005; 23: 3104-3111
- Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial.Lancet. 2007; 370: 135-142
- FOCUS trial investigators; National Cancer Research Institute Colorectal Clinical Studies Group. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial.Lancet. 2007; 370: 143-152
- Cetuximab for the treatment of colorectal cancer.N Engl J Med. 2007; 357: 2040-2048
- Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials.Eur J Cancer. 2012; 48: 1466-1475
- Cetuximab and 1st-Line Chemotherapy in Elderly and Younger Patients with Metastatic Colorectal Cancer (MCRC): a Pooled Analysis of the CRYSTAL and OPUS Studies.Milan, European Cancer Congress2010
- Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer.Br J Cancer. 2012; 106: 274-278
- Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer.Crit Rev Oncol Hematol. 2008; 67: 255-262
- Anti-EGFR (cetuximab) combined with irinotecan for treatment of elderly patients with metastatic colorectal cancer (mCRC).J Cancer Res Clin Oncol. 2012; 138: 1487-1492
- Patterns of use and tolerance of anti-epidermal growth factor receptor antibodies in older adults with metastatic colorectal cancer.Clin Colorectal Cancer. 2014; 13: 192-198
- Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC) — results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care.Ann Oncol. 2011; 22: 118-126
- Panitumumab: a review of its use in metastatic colorectal cancer.Drugs. 2010; 70: 1059-1078
- Epidermal growth factor receptor monoclonal antibodies for the treatment of metastatic colorectal cancer.Pharmacotherapy. 2008; 28: 742-754
- PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer.J Clin Oncol. 2014; 32: 2240-2247
- Final results from a randomized phase 3 study of FOLFIRI ± panitumumab for second-line treatment of metastatic colorectal cancer.Ann Oncol. 2014; 25: 107-116
- 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. 2007; 25: 1658-1664
- Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.J Clin Oncol. 2008; 26: 1626-1634
- Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study.Lancet Oncol. 2014; 15: 569-579
- On behalf of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). First-line single-agent panitumumab in frail elderly patients with wild-type KRAS metastatic colorectal cancer and poor prognostic factors: a phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours.Eur J Cancer. 2015; 51: 1371-1380
- Single-agent panitumumab in frail elderly patients with advanced RAS and BRAF wild-type colorectal cancer: challenging drug label to light up new hope.Oncologist. 2015; 20: 1261-1265
- Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations.J Clin Oncol. 2014; 32: 2587-2594
- Is panitumumab monotherapy safe in metastatic colorectal cancer patients over 70 years old?.in: San Francisco: Gastrointestinal Cancers Symposium. 2015
Article info
Publication history
Published online: February 18, 2016
Accepted:
January 29,
2016
Received in revised form:
January 16,
2016
Received:
October 2,
2015
Identification
Copyright
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
