Feasibility of Capecitabine and Oxaliplatin Combination Chemotherapy Without Central Venous Access Device in Patients With Stage III Colorectal Cancer

doi:10.1016/j.clcc.2015.11.004

Clinical Colorectal Cancer

Volume 15, Issue 3, September 2016, Pages 250-256

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https://doi.org/10.1016/j.clcc.2015.11.004 Get rights and content

Abstract

Background

5-Fluorouracil and leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (XELOX) is a standard adjuvant treatment for patients with stage III colon cancer (CC). Capecitabine is an oral fluoropyrimidine, and administration of oxaliplatin does not necessarily require the insertion of a central venous access device (CVAD). We evaluated the feasibility of XELOX without a CVAD as adjuvant treatment in patients with stage III CC.

Patients and Methods

We retrospectively studied prospectively collected data from patients with stage III CC treated with XELOX in the International Duration Evaluation of Adjuvant Chemotherapy French trial. Patients were divided into 2 groups: those with a CVAD and those with peripheral venous access (PVA), including patients who had and had not had a CVAD at the first cycle of chemotherapy. Chemotherapy without a CVAD was considered feasible if the patient received all cycles of adjuvant therapy without it.

Results

A total of 203 patients were included: 86 (43%) in the PVA group and 116 (57%) in the CVAD group. Of the 85 patients in the PVA group (1 patient was not treated), 69 (81.2%) did not require the insertion of a CVAD. However, 16 (18.8%) required CVAD insertion owing to systematic delay of the initially planned CVAD before the second cycle of chemotherapy in 7, complications related to PVA usage in 5, a switch to the modified FOLFOX6 regimen in 2, and other reasons in 2. The oxaliplatin dose was similar in both groups regardless of the chemotherapy duration. XELOX without a CVAD was feasible for 81.2% of the patients for whom a CVAD had not been planned before chemotherapy and for 88.4% of patients for whom chemotherapy was planned without the use of a CVAD.

Conclusion

XELOX chemotherapy without a CVAD is a feasible approach for treating patients with stage III CC in the adjuvant setting.

Introduction

Colorectal cancer (CRC) is the third most diagnosed cancer in the world and the fourth most common cause of cancer death.¹ The 3-year disease-free survival (DFS) for patients with stage III CRC without any postoperative chemotherapy has ranged from 44% to 52%.2, 3 The standard adjuvant treatment for patients with stage III colon cancer consists of the combination of folinic acid, 5-FU, and oxaliplatin (FOLFOX), administered for 6 months.4, 5, 6, 7

With the intent to improve the quality of life of patients with CRC, the oral drug capecitabine was developed as a substitute for infusional 5-FU/LV in the adjuvant setting. In the phase III Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial of stage III colon cancer (CC), capecitabine was compared to 6 months of the Mayo Clinic 5-FU/LV combination.⁸ Capecitabine yielded at least equivalent DFS to 5-FU/LV. In the multicenter phase III NO16968 trial, which randomized patients with stage III CC to either capecitabine and oxaliplatin (XELOX) for 3 weeks or standard bolus 5-FU/LV, XELOX showed superiority over 5-FU/LV.9, 10 A 3-year DFS of 70.9% with XELOX versus 66.5% with 5-FU/LV and 7-year overall survival of 73% with XELOX versus 67% with 5-FU/LV were observed. These results prompted the adoption of the XELOX regimen as standard adjuvant treatment for stage III CC. The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) phase III multicenter trial was designed to test whether a 3-month course of oxaliplatin-based adjuvant therapy (modified FOLFOX6 or XELOX) is not inferior for DFS to the current 6-month duration of the identical treatment.¹¹

With the XELOX regimen, capecitabine is administered orally, with intravenous administration of oxaliplatin. Given that oxaliplatin is classified as an irritating cytostatic regimen,¹² its administration through a peripheral vein does not induce a severe risk of skin toxicity in the case of extravasation. Oxaliplatin infusion without the need for a central venous access device (CVAD) has been reported in patients with metastatic CRC; however, very few data have been published regarding this aspect.¹³ The placement of an implantable CVAD might not be always justified in patients for whom peripheral venous access (PVA) is sufficient and for those who undergoing XELOX for a maximum duration of 8 cycles, such as in the case of adjuvant chemotherapy for stage III CRC. The IDEA study provided an ideal learning opportunity to compare CVAD XELOX chemotherapy delivery with PVC XELOX administration in patients with stage III CRC.

The present study used an extraction of the IDEA FRANCE database to evaluate the feasibility of XELOX chemotherapy without a CVAD as adjuvant treatment of stage III CC.

Section snippets

Patients

Patients eligible for study inclusion were those with stage III CC and those treated with XELOX (at least as the first course of treatment) in the French IDEA study (ClinicalTrials.gov identifier, NCT00958737; EudraCT number, 2009-010384-16). Patients were excluded from the present analysis if the first cycle of chemotherapy had been the FOLFOX6 modified regimen.

Each patient provided written informed consent before undergoing any study-related procedures. The study was conducted in accordance

Patient Population

A total of 203 of the 2023 patients (10.0%) from the IDEA France database were considered eligible for the present study. Of these, 86 (42.4%) were classified into the PVA group and 116 (57.1%) into the CVAD group. One patient in the PVA group was not treated. The main characteristics of the eligible patients are listed in Table 1. The distribution of patient characteristics at baseline was similar between the 2 groups, except for tumor grade differentiation.

Chemotherapy Administration

In the PVA group, 1 patient was not

Discussion

The results of our study have shown that XELOX chemotherapy without a CVAD is a feasible approach for treating patients with stage III CC in the adjuvant setting. XELOX chemotherapy without a CVAD was successful in 81.2% of patients for whom a CVAD was not planned before the first cycle of chemotherapy and in 88.4% of patients for whom chemotherapy had been planned without the use of CVAD.

The main indication for CVAD includes the need for venous access in patients undergoing prolonged

Conclusion

In the present study, we have demonstrated that XELOX chemotherapy without a CVAD is a feasible approach for treating most patients with stage III CC in the adjuvant setting without adverse consequence in treatment exposure. From a clinical standpoint, our findings contribute toward a better orientation of therapeutic decisions. An appropriate assessment of the patient's venous capital by the nurse or physician can better guide decision on whether a CVAD should be placed, with the aim of

Disclosure

B. Chibaudel reports personal fees for consultancy from Roche and Sanofi. O Bouché reports personal fees from Roche, Merck-Sereno, and Amgen. A Lièvre reports honoraria from Merck Serono, Amgen, Sanofi, and Roche. T André reports personal fees from Roche, Amgen, Sanofi, and Merck. No potential conflicts of interest were disclosed by the other authors.

Acknowledgments

The authors thank the patients, their caregivers, and all the study investigators listed: Albert Aleba (Centre Hospitalier Niort, Niort), Jean-Baptiste Bachet (Groupe Hospitalier Universitaire Pitié Salpetrière, Paris), Julien Baudon (Centre Hospitalier de Cholet, Cholet), Isabelle Baumgaertner (Centre Hospitalier Universitaire Henri Mondor, Creteil), Yves Becouarn (Institut Bergonié, Bordeaux), Nathalie Bonichon-Lamichhane (Clinique Tivoli, Bordeaux), Christian Borel (Centre Régional de Lutte

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Cited by (11)

Non-metastatic colon cancer: French Intergroup Clinical Practice Guidelines for diagnosis, treatments, and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, AFEF, and SFR)
2024, Digestive and Liver Disease
This article is a summary of the French intergroup guidelines regarding the management of non-metastatic colon cancer (CC), revised in November 2022.
These guidelines represent collaborative work of all French medical and surgical societies involved in the management of CC. Recommendations were graded in three categories (A, B, and C) according to the level of evidence found in the literature published up to November 2022.
Initial evaluation of CC is based on clinical examination, colonoscopy, chest-abdomen-pelvis computed tomography (CT) scan, and carcinoembryonic antigen (CEA) assay. CC is usually managed by surgery and adjuvant treatment depending on the pathological findings. The use of adjuvant therapy remains a challenging question in stage II disease. For high-risk stage II CC, adjuvant chemotherapy must be discussed and fluoropyrimidine monotherapy or oxaliplatin-based chemotherapy proposed according to the type and number of poor prognostic features. Oxaliplatin-based chemotherapy (FOLFOX or CAPOX) is the current standard for adjuvant therapy of patients with stage III CC. However, these regimens are associated with significant oxaliplatin-induced neurotoxicity. The results of the recent IDEA study provide evidence that 3 months of treatment with CAPOX is as effective as 6 months of oxaliplatin-based therapy in patients with low-risk stage III CC (T1–3 and N1). A 6-month oxaliplatin-based therapy remains the standard of care for high-risk stage III CC (T4 and/or N2). For patients unfit for oxaliplatin, fluoropyrimidine monotherapy is recommended.
French guidelines for non-metastatic CC management help to offer the best personalized therapeutic strategy in daily clinical practice. Each individual case must be discussed within a multidisciplinary tumor board and then the treatment option decided with the patient.
Vascular access device type for systemic anti-cancer therapies in cancer patients: A scoping review
2024, Critical Reviews in Oncology/Hematology
Patients with cancer can expect to receive numerous invasive vascular access procedures for intravenous therapy and clinical diagnostics. Due to the increased incidence and prevalence of cancer globally there will be significantly more people who require first-line intravenous chemotherapy over the next ten years.
Our objective was to determine the types of evidence that exist for the vascular access device (VAD) type for the delivery of systemic anti-cancer therapy (SACT) in cancer patients. We used JBI scoping review methodology to identify the types of VADs used for SACT and with a specific search strategy included articles from 2012–2022 published in the English language. We identify (i) type of VADs used for SACT delivery (ii) the type of insertion and post-insertion complications (iii) the geographical location and clinical environment (iv) and whether VAD choice impacts on quality of life (QOL). Findings were presented using the PAGER framework.
Our search strategy identified 10,390 titles, of these, 5318 duplicates were removed. The remaining 5072 sources were screened for eligibility, 240 articles met the inclusion criteria. The most common design include retrospective study designs (n = 91) followed by prospective study designs (n = 31). We found 28 interventional studies with 21 registered in a clinical trial registry and identified no core outcome sets papers specific to VAD for SACT. The most prevalent publications were those that featured two or more VAD types (n = 70), followed by tunnelled intravenous VADs (n = 67). Of 38 unique complications identified, the most frequent catheter related complication was catheter related thrombosis (n = 178, 74%), followed by infection (n = 170, 71%). The county where the most publications originated from was China (n = 62) with one randomized controlled multicenter study from a comprehensive cancer centre. Of the thirty three studies that included QOL we found 4 which reported on body image. No QOL measurement tools specific to the process of SACT administration via VAD are available
Our findings suggest a systematic review and meta-analysis of VAD use for intravenous SACT can be considered. However, the development of a core outcome set for SACT should be prioritised. Funding for high quality programs of research for VAD in cancer are needed. Comprehensive cancer centres should lead this research agenda.
Impact of the IDEA Collaboration Study Results on Clinical Practice in France for Patients With Stage III Colon Cancer: A National GERCOR - PRODIGE Survey
2021, Clinical Colorectal Cancer
Citation Excerpt :
One-third of the physicians used CVAD for patients treated with CAPOX for 3 months, despite good venous capital. The feasibility of treating patients with CAPOX on a peripheral venous access for 3 or 6 months has been demonstrated in an analysis of 203 patients included in the IDEA France study: CAPOX adjuvant chemotherapy without a CVAD was successful in 88.4% of patients for whom chemotherapy had been planned without the use of CVAD.14 The reason why one-third of physicians use central venous devices needs to be explored.
The IDEA collaboration showed that the type and duration of adjuvant chemotherapy in stage III colon cancer (CC) could be adjusted according to the schedule of chemotherapy and the level of risk. We aimed at evaluating the implementation of IDEA’s results in real-life practice for stage III CC.
All clinicians registered in the French oncology cooperative groups GERCOR, FFCD, and UNICANCER GI mailing lists were invited to participate to an online anonymized nationwide survey from January 30, 2019 to March 31, 2019. Proportions were compared using the χ² test.
A total of 213 physicians answered the survey. Of these, 173 (81%) considered that 3 months of adjuvant chemotherapy was the new standard of care for low-risk (pT1-3/N1) stage III CC, and 99% considered that 6 months remained the standard of care for high-risk (pT4 and/or pN2) stage III CC. In patients under 70 years, capecitabine and oxaliplatin (CAPOX) for 3 months was prescribed by 74% of the participants in low-risk CC, whereas 6 months of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was preferred for high-risk CC in 94% of cases. For patients over 70 years with good performance status and no comorbidities, 172 (81%) physicians prescribed oxaliplatin-based chemotherapy for low-risk CC (3 months, 144 of 172%; 88%), and 200 (94%) physicians prescribed oxaliplatin-based adjuvant chemotherapy for high-risk CC (6 months, 199 of 200%; 99.5%).
The IDEA results have been practice-changing as French physicians have implemented 3 months of CAPOX for patients with low-risk stage III CC, substituting from 6 months of FOLFOX, which remains the preferred regimen for high-risk patients.
Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials
2020, The Lancet Oncology
Citation Excerpt :
The administration of FOLFOX is cumbersome because doing so requires the implantation of a venous access device and the use of an infusion pump. Capecitabine, an oral fluoropyrimidine, combined with oxaliplatin intravenously every 3 weeks is more convenient for most patients, less expensive for the health-care system in most countries, and does not require the placement of a venous access device for most patients, especially if the duration of treatment is only 3 months, corresponding to only four intravenous administrations of oxaliplatin.26 Because no randomisation to either FOLFOX or CAPOX was done in this study, we could not assess whether 3 months of CAPOX was as good as 6 months of FOLFOX.7
A prospective, pooled analysis of six randomised phase 3 trials was done to investigate disease-free survival regarding non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer; non-inferiority was not shown. Here, we report the final overall survival results.
In this prospective, pooled analysis of six randomised phase 3 trials, we included patients with stage III colon cancer aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0–1 recruited between June 20, 2007, and Dec 31, 2015, across 12 countries in the CALGB/SWOG 80702, IDEA France, SCOT, ACHIEVE, TOSCA, and HORG trials, who started any treatment (modified intention-to-treat). Patients in all trials were randomly assigned to 3 months or 6 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) every 2 weeks or capecitabine and oxaliplatin (CAPOX) in different doses and methods every 3 weeks, at the treating physician's discretion. The primary endpoint was disease-free survival (time to relapse, secondary colorectal primary tumour, or death due to all causes), and overall survival (time to death due to all causes) was the prespecified secondary endpoint. The non-inferiority margin for overall survival was set as a hazard ratio (HR) of 1·11. Pre-planned subgroup analyses included regimen and risk group. Non-inferiority was declared if the one-sided false discovery rate adjusted (FDRadj) p value was less than 0·025.
With median follow-up of 72·3 months (IQR 72·2–72·5), 2584 deaths among 12 835 patients were observed. 5064 (39·5%) patients received CAPOX and 7771 (60·5%) received FOLFOX. 5-year overall survival was 82·4% (95% CI 81·4–83·3) with 3 months of therapy and 82·8% (81·8–83·8) with 6 months of therapy (HR 1·02 [95% CI 0·95–1·11]; non-inferiority FDRadj p=0·058). For patients treated with CAPOX, 5-year overall survival was 82·1% (80·5–83·6) versus 81·2% (79·2–82·9; HR 0·96 [0·85–1·08]); non-inferiority FDRadj p=0·033), and for patients treated with FOLFOX 5-year overall survival was 82·6% (81·3–83·8) and 83·8% (82·6–85·0; HR 1·07 [0·97–1·18]; non-inferiority FDRadj p=0·34). Updated disease-free survival results confirmed previous findings (HR 1·08 [95% CI 1·02–1·15]; non-inferiority FDRadj p=0·25). Data on adverse events were not further recorded.
Non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer was not confirmed in terms of overall survival, but the absolute 0·4% difference in 5-year overall survival should be placed in clinical context. Overall survival results support the use of 3 months of adjuvant CAPOX for most patients with stage III colon cancer. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies, and cost associated with a shorter treatment duration.
US National Cancer Institute.
Oncology nurses’ knowledge about exploring chemotherapy related - Extravasation care: A cross-sectional study
2020, Clinical Epidemiology and Global Health
Citation Excerpt :
It is defined as accidental damage of subcutaneous tissue or perivascular space related to leakage of the cytotoxic drug.6 The severity of damage depends on the amount and type of leaked drug, time, and toxicity.7 Because of shortage in reporting and registration of chemotherapy extravasation events; the incidence of extravasation varies.
can cause significant tissue damage; alter limb function, pain and decreasing quality of life. Nurses play a significant role in the prevention, identification and follow-up of the complications.
This study was conducted to evaluate the oncology nurses’ knowledge about chemotherapy related - extravasation injuries, risk factors, preventive measures, and management practices.
A descriptive cross-sectional design with a convenience sample was used. A sample of 110 oncology nurses completed the knowledge test. European Society for Medical Oncology (ESMO) - European Oncology Nursing Society (EONS) management of chemotherapy extravasation Clinical practice guidelines were used to develop the knowledge test.
The oncology nurses' knowledge of chemotherapy related-extravasation's definition and signs and symptoms was satisfactory. However, knowledge about risk factors was limited. Generally, the results showed that high percentage of the participants had correct information regarding the procedure domain. However, knowledge deficit regarding site of insertion, and cannula characteristics were reported. The results showed that there was knowledge deficit among the participants regarding all specific treatment practices.
The current study provides a baseline data about oncology nurses knowledge and practice regarding chemotherapy related-extravasation care. Continues education, seminars, and workshops should be conducted for oncology nurses to increase their knowledge and strengthen their competencies.
Locust bean gum and sodium alginate based interpenetrating polymeric network microbeads encapsulating Capecitabine: Improved pharmacokinetics, cytotoxicity &in vivo antitumor activity
2019, Materials Science and Engineering C
Citation Excerpt :
So far, fluoropyrimidines are the most preferred agents utilized during chemotherapy [3]. Capecitabine, a carbamic acid derivative and a prodrug of 5-Fluoropyrimidine (5-FU) has emerged out as a successful agent alone or in the combination such as oxaliplatin or irinotecan for the treatment of early stage and advanced stage colorectal cancer [4]. Though CAP sounds an effective drug with good water solubility and bioavailability, but its high dose (1250 mg/m2), elimination half-life of 0.5–1 h and associated severe side effects bone marrow depression, cardiotoxicity, dermatitis, diarrhea, nausea, vomiting etc. requires a suitable formulation that can circumvent the entire problems related with CAP [5].
A combination of biopolymers sodium alginate and locust bean gum has been used to prepare an interpenetrating polymeric network of an anticancer drug Capecitabine by ionotropic gelation method. For the optimization 3² levels, a full factorial design was employed to examine the influence of independent factors, i.e. polymer ratio and cross-linker concentration on responses particle size and drug entrapment. The obtained optimized formulation was examined for solid-state characterization, swelling study, in vitro drug release, SRB study, oral toxicity study, in vivo pharmacokinetic and in vivo antitumor study. The results of all the studies performed were found suitable in extending the release of a short elimination half-life drug with improved bioavailability and suggesting it to be safe and effective for oral drug delivery in treating colon cancer.

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Original StudyFeasibility of Capecitabine and Oxaliplatin Combination Chemotherapy Without Central Venous Access Device in Patients With Stage III Colorectal Cancer

Abstract

Background

Patients and Methods

Results

Conclusion

Introduction

Section snippets

Patients

Patient Population

Chemotherapy Administration

Discussion

Conclusion

Disclosure

Acknowledgments

Ann Oncol

Eur J Cancer

Ann Oncol

GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11

Levamisole and fluorouracil as adjuvant therapy of resected colon carcinoma

N Engl J Med

Efficacy of adjuvant fluorouracil and folinic acid in colon cancer

Lancet

Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial

J Clin Oncol

Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07

J Clin Oncol

Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses

J Clin Oncol

Multicenter international study of oxaliplatin/5-fluorouracil/leucovorin in the adjuvant treatment of colon cancer (MOSAIC) investigators: oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer

N Engl J Med

Capecitabine as adjuvant treatment for stage III colon cancer

N Engl J Med

Original Study
Feasibility of Capecitabine and Oxaliplatin Combination Chemotherapy Without Central Venous Access Device in Patients With Stage III Colorectal Cancer