Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study

Rosati, Gerardo; Cordio, S.; Bordonaro, Roberto; Caputo, G; Novello, G.; Reggiardo, Giorgio; Manzione, Luigi

doi:10.1093/annonc/mdp359

Cited by 45 publications

(40 citation statements)

References 28 publications

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“…In the first-line setting with SOx we observed a response rate of 41%, DCR of 86%, median PFS of 8.5 months and median OS of 18.5 months, data which are in line with what would be expected in older mCRC patients treated with chemotherapy [18,19]. Our findings indicate that the SOx regimen is well tolerated even in older patients with a low rate of clinical adverse events similar to what would be expected with other fluoropyrimidine-oxaliplatin-based combinations, albeit with a much lower rate of HFS [20].…”

Section: Discussionsupporting

confidence: 89%

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review

et al. 2016

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Background: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. Material and methods: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. Results: From June 2012 to December 2014, 71 older patients received 1 cycle of either S-1 (n ¼ 9), SOx (n ¼ 44) or IRIS (n ¼ 18) for mCRC. Median age was 76 years and most patients had a WHO performance status of 0 (32%) or 1 (56%). All patients were evaluable for response and safety. In the SOx group, 18 (41%) and 20 patients (45%) had partial response (PR) and stable disease (SD), respectively (disease control rate 86%). Median progression-free survival (PFS) was 8.5 months and median overall survival (OS) was 18.5 months. In the S-1 group (median age 82 years), PR was 22%, median PFS 6.4 months and median OS 15.8 months. In the IRIS group, PR was 28%, median PFS 7.8 months and the median OS 16.5 months. In general, therapy was well tolerated; main non-hematological toxicities were fatigue and diarrhea. Conclusion: S-1 monotherapy, SOx and IRIS were well tolerated for older patients with mCRC and could become alternative regimens in older mCRC patients. These regimens are now further evaluated in the randomized ongoing NORDIC9 trial.

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Section: Discussionsupporting

confidence: 89%

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review

et al. 2016

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“…Inclusion criteria for the NMA were in line with the PICO (population, intervention, comparator, outcome) criteria specified in the NICE scope 14 84,87,88,92 were excluded from the primary analysis because of population differences or differences in the treatment regimen administered. Based on the 17 RCTs, Amgen built one network.…”

Section: Network Meta-analysismentioning

confidence: 99%

“…41-2 and pp. [87][88][89][90][91][92][93][94][95][96][97] and full results (including the results of the sensitivity analyses conducted) were reported (appendix 8, pp. 87-97).…”

Section: Network Meta-analysismentioning

confidence: 99%

“…Of the studies included in Amgen's NMA [n = 21, reported in 22 publications 28 [78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94] The reason for their exclusion was that they did not evaluate the effectiveness of the interventions in the RAS WT population. In addition to the abstracts for the OPUS 33 and CRYSTAL 34 trials included in the Amgen NMA, the Assessment Group identified the full publications.…”

Section: Comparison With the Assessment Group's Network-meta-analysismentioning

confidence: 99%

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The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation

Huxley

Crathorne

Varley-Campbell

et al. 2017

Health Technol Assess

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BackgroundColorectal cancer is the fourth most commonly diagnosed cancer in the UK after breast, lung and prostate cancer. People with metastatic disease who are sufficiently fit are usually treated with active chemotherapy as first- or second-line therapy. Targeted agents are available, including the antiepidermal growth factor receptor (EGFR) agents cetuximab (Erbitux®, Merck Serono UK Ltd, Feltham, UK) and panitumumab (Vecitibix®, Amgen UK Ltd, Cambridge, UK).ObjectiveTo investigate the clinical effectiveness and cost-effectiveness of panitumumab in combination with chemotherapy and cetuximab in combination with chemotherapy for rat sarcoma (RAS) wild-type (WT) patients for the first-line treatment of metastatic colorectal cancer.Data sourcesThe assessment included a systematic review of clinical effectiveness and cost-effectiveness studies, a review and critique of manufacturer submissions, and a de novo cohort-based economic analysis. For the assessment of effectiveness, a literature search was conducted up to 27 April 2015 in a range of electronic databases, including MEDLINE, EMBASE and The Cochrane Library.Review methodsStudies were included if they were randomised controlled trials (RCTs) or systematic reviews of RCTs of cetuximab or panitumumab in participants with previously untreated metastatic colorectal cancer withRASWT status. All steps in the review were performed by one reviewer and checked independently by a second. Narrative synthesis and network meta-analyses (NMAs) were conducted for outcomes of interest. An economic model was developed focusing on first-line treatment and using a 30-year time horizon to capture costs and benefits. Costs and benefits were discounted at 3.5% per annum. Scenario analyses and probabilistic and univariate deterministic sensitivity analyses were performed.ResultsThe searches identified 2811 titles and abstracts, of which five clinical trials were included. Additional data from these trials were provided by the manufacturers. No data were available for panitumumab plus irinotecan-based chemotherapy (folinic acid + 5-fluorouracil + irinotecan) (FOLFIRI) in previously untreated patients. Studies reported results forRASWT subgroups. First-line treatment with anti-EGFR therapies in combination with chemotherapy appeared to have statistically significant benefits for patients who areRASWT. For the independent economic evaluation, the base-case incremental cost-effectiveness ratio (ICER) forRASWT patients for cetuximab plus oxaliplatin-based chemotherapy (folinic acid + 5-fluorouracil + oxaliplatin) (FOLFOX) compared with FOLFOX was £104,205 per quality-adjusted life-year (QALY) gained; for panitumumab plus FOLFOX compared with FOLFOX was £204,103 per QALY gained; and for cetuximab plus FOLFIRI compared with FOLFIRI was £122,554 per QALY gained. The ICERs were sensitive to treatment duration, progression-free survival, overall survival (resected patients only) and resection rates.LimitationsThe trials includedRASWT populations only as subgroups. No evidence was available for panitumumab plus FOLFIRI. Two networks were used for the NMA and model, based on the different chemotherapies (FOLFOX and FOLFIRI), as insufficient evidence was available to the assessment group to connect these networks.ConclusionsAlthough cetuximab and panitumumab in combination with chemotherapy appear to be clinically beneficial forRASWT patients compared with chemotherapy alone, they are likely to represent poor value for money when judged by cost-effectiveness criteria currently used in the UK. It would be useful to conduct a RCT in patients withRASWT.Study registrationThis study is registered as PROSPERO CRD42015016111.FundingThe National Institute for Health Research Health Technology Assessment programme.

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“…New studies are mandatory to establish particularly the safety of various combinations plus or minus biological agents in older patients. In this context, the results of a randomized phase Ⅱ study evaluating the activity and safety of capecitabine in combination with oxaliplatin (CAPOX) or with irinotecan (CAPIRI) in patients ≥ 70 years could be of interest [66] . Preliminary data from this trial confirm both combinations are active (RR 38.4% for CAPIRI and 32.2% for CAPOX) with median response durations of 8.2 mo for CAPIRI and 6 mo for CAPOX.…”

Section: Resultsmentioning

confidence: 99%

Role of chemotherapy and novel biological agents in the treatment of elderly patients with colorectal cancer

Rosati¹,

Bilancia²

2008

WJG

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Patients older than 65 years are the fastest growing segment of the cancer population. It is estimated that within 20 years over 75% of cases and 85% of deaths from colorectal cancer (CRC) will be in this setting. Concerns about cancer treatment in the elderly relate to comorbidities, which increase proportionally with age, physiological changes associated with aging which may influence drug metabolism and toxicity, and diminishing life expectancy, which particularly impacts decisions surrounding the benefits of adjuvant therapies. Over the last 10 years, significant improvements in the treatment of advanced CRC with combination therapy have been made. The randomized trials which have defined these improvements did not exclude elderly patients. However, the median age of patients in these trials has generally been approximately 60 years. Thus, it appears that some degree of selection is involved with younger and presumably fitter patients being the subjects in most of the pivotal trials. The availability of new molecularly targeted agents and newly improved existing agents has expanded the range of treatment options available. This variety gives greater flexibility in dealing with different subsets of patients, such as the elderly. However, some fit elderly patients seem to tolerate combination therapy reasonably well, while studies on unfit elderly subjects are needed.

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Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study

Abstract: CAPOX and CAPIRI had similar efficacy in elderly patients, although CAPOX seemed to be better tolerated.

Cited by 45 publications

References 28 publications

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review

The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation

Role of chemotherapy and novel biological agents in the treatment of elderly patients with colorectal cancer

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