Intensity of adjuvant chemotherapy regimens and grade III–V toxicities among elderly stage III colon cancer patients

Erning, Felice N. van; Razenberg, Lieke G.E.M.; Lemmens, Valery; Creemers, Geert-Jan; Pruijt, J.F.M.; Maas, Huub; Janssen‐Heijnen, M.L.G.

doi:10.1016/j.ejca.2016.03.074

Cited by 18 publications

(33 citation statements)

References 34 publications

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“…Except for the finding that male patients more often completed all planned cycles of CAPOX than female patients, no other differences in patient and tumor characteristics were found between patients who completed all planned cycles and patients who did not complete all planned cycles, for both CAPOX and CapMono. In a previous study from our group, we found that only the presence of any grade III‐V toxicity was related to early treatment discontinuation for both CAPOX and CapMono . The completion rates are lower than those found in other studies.…”

Section: Discussioncontrasting

confidence: 62%

“…Nowadays, in the Netherlands CAPOX and capecitabine monotherapy (CapMono) are the mostly prescribed regimens for elderly stage III colon cancer patients treated in daily clinical practice. A significant part of the elderly treated with adjuvant chemotherapy however do not complete all planned cycles . Previous studies have shown that patients who failed to complete chemotherapy treatment with FU/LV exhibited a worse cancer‐specific survival than those who completed treatment, while early discontinuation of FOLFOX did not affect disease‐free and overall survival …”

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confidence: 99%

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Recurrence‐free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy

Erning

Janssen‐Heijnen

Creemers

et al. 2016

Intl Journal of Cancer

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The aim of this study is to investigate the effects of CAPOX and capecitabine on recurrence-free survival (RFS) and overall survival (OS) among elderly stage III colon cancer patients and to evaluate the effect of (non-)completion. Patients aged 70 years who underwent resection only or who were subsequently treated with CAPOX or capecitabine in 10 large non-academic hospitals were included. RFS and OS were analyzed with Kaplan-Meier curves and multivariable Cox regression adjusted for patient and tumor characteristics. 982 patients were included: 630 underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five-year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60% (p 5 0.91), adjusted HR 5 0.99 (95%CI 0.68-1.44); OS: 66% vs. 66% (p 5 0.76), adjusted HR 5 0.93 (95%CI 0.64-1.34)). After resection only, RFS was 38% and OS 37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three-year RFS and OS did not differ between patients who discontinued CAPOX early and patients who completed treatment with CAPOX (RFS: 61% vs. 69% (p 5 0.21), adjusted HR 5 1.42 (95%CI 0.85-2.37); OS: 68% vs. 78% (p 5 0.41), adjusted HR 5 1.17 (95%CI 0.70-1.97)). Three-year RFS and OS differed between patients who discontinued capecitabine early and patients who completed treatment with capecitabine (RFS: 54% vs. 72% (p 5 0.01), adjusted HR 5 2.07 (95%CI 1.11-3.84); OS: 65% vs. 80% (p 5 0.01), adjusted HR 5 2.00 (95%CI 1.12-3.59)). Receipt of CAPOX or capecitabine is associated with improved RFS and OS. The advantage does not differ by regimen. The addition of oxaliplatin might not be justified in elderly stage III colon cancer patients.Adjuvant chemotherapy is standard care for patients with stage III colon cancer. Several randomized controlled trials have been performed to compare the effectiveness of a number of agents in this setting. In the X-ACT trial, oral capecitabine demonstrated to be as effective as 5FU/LV, with an improved safety profile except for more hand-foot syndrome. 1,2 The MOSAIC trial and NSABP C-07 study showed that oxaliplatin in combination with 5-flourouracil/leucovorin (FOLFOX) provided an additional 4% survival gain compared to 5FU/LV alone, but at the cost of higher toxicity rates, especially significant neurotoxicity. [3][4][5][6] In the XELOXA trial, the combination of oxaliplatin with capecitabine (CAPOX) also improved disease-free and overall survival compared with bolus fluorouracil/folinic acid (FU/FA) and was shown to provide an alternative treatment option, but with higher rates of grade III-IV neurotoxicity and grade III hand-foot syndrome. 7-9 Up to date, no randomized controlled trial compared FOLFOX and CAPOX head to head in the adjuvant setting and therefore both are considered standard care. Despite the fact that patients aged 70 years account for more than half of the patients with colon cancer, 10 only a small part of this group is included in clinical trials. Subgroup analyses of trials by age group have shown that oral capecitabine maintained...

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Section: Discussioncontrasting

confidence: 62%

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confidence: 99%

Recurrence‐free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy

Erning

Janssen‐Heijnen

Creemers

et al. 2016

Intl Journal of Cancer

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“…In most studies, elderly patients were found to experience more adverse events related to the use of capecitabine [7, 8, 12], although one study [13] showed no difference in the incidence of grade 3 or 4 adverse events between patients aged older than 80 years and the overall population. The impact of these adverse effects on patient quality of life, treatment compliance, and disease-related outcomes in the elderly is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Real-World Adverse Effects of Capecitabine Toxicity in an Elderly Population

Beek¹,

Roukens²,

Jacobs³

et al. 2018

Drugs - Real World Outcomes

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BackgroundFew studies have assessed the safety and effectiveness of the numerous available chemotherapeutic therapies for geriatric oncology patients. Most safety studies are conducted in large trials, and there is some uncertainty surrounding whether the results would be the same in typical daily use.ObjectiveThis retrospective study aims to assess the adverse effects of real-world capecitabine use in elderly patients.MethodsWe reviewed the records of patients treated with capecitabine in an oncology department of a University Clinic in Nijmegen, The Netherlands. We scored adverse effects such as hand-foot syndrome and diarrhea, and dosage adjustments and the reasons for them. In total, 132 patients were included, 69 of whom were aged 70 years or below (mean age: 57 years), while 63 were aged older than 70 years (mean age: 74 years).ResultsPatients aged over 70 years experienced more serious adverse effects than younger patients. Grade 2 or 3 hand-foot syndrome toxicity was experienced by 20.2% of patients aged younger than 70 years and by 34.9% of patients older than 70 years (p = 0.059). Grade 2, 3, or 4 diarrhea was experienced by 17.4% of the patients aged younger than 70 years but by 31.7% of the patients aged older than 70 years (p = 0.044). Dosage was adjusted for 27/69 patients in the younger group and 52/63 patients in the older group (p = 0.001).ConclusionThe difference in observed adverse effects cannot be the sole explanation for the high incidence of observed dose adjustments. A prospective follow-up study of elderly patients using capecitabine outside clinical trials is needed to evaluate the optimum balance between adverse effects and efficacy.

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“…In the MOSAIC Trial (2004), patients randomized to 5‐flourouracil plus oxaliplatin (FOLFOX) had a significantly higher odds of discontinuation than those randomized to 5‐flourouracil alone (OR: 2.16; 95% CI: 1.74‐2.69) . Similarly, van Erning (2016) found that patients aged 70 + years who were prescribed capecitabine plus oxaliplatin (CAPOX) in a real‐world setting had a higher odds of discontinuation relative to those prescribed capecitabine monotherapy (OR: 2.51; 95% CI: 1.63‐3.86) . In contrast, Abrams et al (2011) found that, in a real‐world cancer patient population, combination therapy was associated with a reduced odds of discontinuation relative to monotherapy (OR: 0.78; 95% CI: 0.62‐0.98) .…”

Section: Resultsmentioning

confidence: 99%

“…From an initial 3927 articles, 18 investigations were identified for inclusion in our review (14 observational studies and four randomized trials) ( Figure 1 and Table 2). [3][4][5][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Among the observational studies, the pooled estimate of the proportion of patients who discontinued chemotherapy was 25.1% (95% CI: 18.3%-33.3%) ( Figure 2). There was substantial heterogeneity in these estimates, likely arising from the disparity in the definitions of chemotherapy discontinuation (I 2 : 98.8%; tau 2 : 0.567; 95% prediction interval: 6.8%-60.7%).…”

Section: Systematic Reviewmentioning

confidence: 99%

Prognostic factors of adjuvant chemotherapy discontinuation among stage III colon cancer patients: A survey of medical oncologists and a systematic review and meta‐analysis

et al. 2020

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Background Factors that are prognostic of early discontinuation of adjuvant chemotherapy among stage III colon cancer patients have yet to be described. To address this gap, a survey of medical oncologists and a systematic review and meta‐analysis were conducted. Methods A survey was distributed in March 2019 to medical oncologists who treat colon cancer within Alberta, Canada. Clinicians were asked to rank the prognostic importance of a set of variables using a Likert scale and agreement was quantified using a weighted Cohen's kappa. In addition, we systematically searched four databases up to July 2019. Meta‐analyses were conducted using a random‐effects model. Results Of the 25 clinicians who were sent the survey, 14 responded. Overall, there was no agreement regarding which variables were prognostic of early discontinuation (weighted Cohen's kappa = 0.12; 95% CI = 0.05‐0.18). From an initial 3927 articles, 18 investigations were identified for inclusion in our review. Based upon evidence from both the survey and the systematic review, the following four variables were identified as being prognostic of early discontinuation: (a) comorbidity (OR2+ vs 0 = 1.53; 95% CI = 1.30‐1.79); (b) performance status (ORECOG 2+ vs 0‐1 = 1.33; 95%CI = 1.07‐1.65); (c) T stage (ORT4 vs T1‐2 = 1.57; 95% CI = 0.99‐2.50); and (d) chemotherapy regimen (estimates not pooled due to heterogeneity). In addition to these factors, there was some suggestion that age, marital status/social support, muscle mass, N stage, and tumor grade had prognostic value. Conclusions Current evidence is heterogeneous and limited. Additional research is needed to confirm our findings and to explore additional prognostic factors.

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Intensity of adjuvant chemotherapy regimens and grade III–V toxicities among elderly stage III colon cancer patients

Cited by 18 publications

References 34 publications

Recurrence‐free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy

Recurrence‐free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy

Real-World Adverse Effects of Capecitabine Toxicity in an Elderly Population

Prognostic factors of adjuvant chemotherapy discontinuation among stage III colon cancer patients: A survey of medical oncologists and a systematic review and meta‐analysis

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