Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study

Rothenberg, Mace L.; Cox, John V.; Butts, Charles; Navarro, Matilde; Bang, Yung Jue; Goel, Rakesh; Gollins, Simon; Siu, Lillian L.; Laguerre, Shelly; Cunningham, David

doi:10.1093/annonc/mdn370

Cited by 172 publications

(135 citation statements)

References 18 publications

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“…Recently, more attention has been paid to combination chemotherapy of CRC with the regimen of capecitabine and oxaliplatin for safe, reliable and convenient medication. In certain randomized studies it was concluded that XELOX is non-inferior in terms of efficacy to the FOLFOX regimen in the first-line treatment of MCRC (5)(6)(7)9,11 Regarding adverse reactions during treatment, 5% of patients had Grade ≥3 hematologic toxicity, 8% of patients had Grade 3 peripheral neuropathy and 13% of patients had severe hand-foot syndrome (19). Similar results were obtained in another phase II trial that included a total of 50 patients aged ﹥70 years with MCRC, using the XELOX regimen as first-line therapy.…”

Section: Study (Year Reference) Pfs (Month) Median Os (Month) ------mentioning

confidence: 99%

Capecitabine plus oxaliplatin compared with 5-fluorouracil plus oxaliplatin in metastatic colorectal cancer: Meta-analysis of randomized controlled trials

et al. 2012

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Abstract. The aim of this study was to evaluate the curative effects and safety of capecitabine plus oxaliplatin compared with 5-fluorouracil (5-FU) plus oxaliplatin in patients with metastatic colorectal cancer (MCRC). We searched the Cochrane Central register of Controlled Trials (CENTRAL), PubMed, Ovid, ScienceDirect, EBSCO, EMBASE and conference proceedings for eligible trials. A meta-analysis was performed using Review Manager 5.0. A total of 3,603 cancer patients from 7 trials were analyzed, and the baseline patient characteristics were comparable in all studies. Curative effect outcomes including complete response (CR) (OR= 0.78; 95% CI 0.47-1.31; p= 0.35), partial response (PR) (OR= 0.81; 95% CI 0.65-1.00; p=0.05) and the overall response rate (ORR) (OR=0.85; 95% CI 0.71-1.02; p=0.08) showed similar curative effects between the capecitabine plus oxaliplatin group and the 5-FU plus oxaliplatin group. Moreover, the median overall survival (OS) and progression-free survival (PFS) had no statistically significant differences. Regarding safety, hand-foot syndrome was more frequently observed in the capecitabine plus oxaliplatin group (OR=2.71; 95% CI 2.04-3.61; p<0.00001), while stomatitis and neutropenia were reversed. Other toxic effects had no statistically significant differences between the two groups. Our results showed that capecitabine plus oxaliplatin had similar curative effects to 5-FU plus oxaliplatin, however, it was safer in patients with MCRC.

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Section: Study (Year Reference) Pfs (Month) Median Os (Month) ------mentioning

confidence: 99%

Capecitabine plus oxaliplatin compared with 5-fluorouracil plus oxaliplatin in metastatic colorectal cancer: Meta-analysis of randomized controlled trials

et al. 2012

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“…Toxicity. (17) showed that xELOx was statistically as effective as FOLFOx-4 when administered as a second-line treatment in patients with metastatic colorectal cancer (median progression-free survival, 4.7 vs. 4.8 months; median overall survival, 11.9 vs. 12.5 months). In summary, the results of these Phase III studies showed that capecitabine could replace 5FU/LV infusions.…”

Section: Discussionmentioning

confidence: 99%

Phase I trial of oxaliplatin plus S-1 chemotherapy in patients with metastatic colorectal cancer

Emi¹,

Yamaguchi²,

Hihara³

et al. 2010

Oncology Letters

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Abstract. Advanced colorectal cancer can be effectively treated with s-1, as well as with a combination of oxaliplatin, 5-fluorouracil (5FU) and leucovorin (LV). However, S-1 together with oxaliplatin may provide a more convenient alternative to 5FU/LV. To evaluate the performance of S-1 combined with oxaliplatin for patients with colorectal cancer, we conducted a Phase I clinical trial in an outpatient setting. We administered s-1 to 15 patients with advanced colorectal adenocarcinoma for two weeks followed by one week of rest. Oxaliplatin was also administered on day 1 of the S-1 cycle. The dose of oxaliplatin was increased from 40 to 85 mg/m 2 to define the maximum tolerated dose and recommended dose in preparation for a Phase II trial. We administered 102 courses of treatment to 15 patients. Grade 3 thrombocytopenia developed in only 1 patient at a dose of 85 mg/m 2 of oxaliplatin plus oral S-1. No other grade 3-4 toxicities developed. No dose-limiting toxicity developed at level 4 of our regimen (oxaliplatin 85 mg/m 2 ), and the recommended dose for a Phase II trial was 85 mg/m 2 of oxaliplatin in an outpatient setting.

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“…The XELOX regimen was associated with a higher frequency and severity of diarrhea, thrombocytopenia and HFS, whereas FOLFOX-4 was associated with more grade 3/4 neutropenia. However, as it was shown that the efficacies of the different treatment regimens are equivalent in metastatic gastrointestinal tumors (9)(10)(11)(12)(13)(14), the use of an oral chemotherapeutic regimen is certainly more comfortable for outpatients and thus certainly positively influences the compliance of patients.…”

Section: Discussionmentioning

confidence: 99%

Combination therapies with oxaliplatin and oral capecitabine or intravenous 5-FU show similar toxicity profiles in gastrointestinal carcinoma patients if hand-food syndrome prophylaxis is performed continuously

et al. 2012

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Abstract. The use of anticancer drugs in palliative settings is often limited by their severe toxic effects. In gastrointestinal carcinomas the 5-fluorouracil-based palliative regimen FOLFOX-4 is often preferred to the equally effective, but more convenient oral capecitabine-based regimen XELOX. This preference is mainly based on the fact that the highly effective oral agent capecitabine induces hand-foot syndrome (HFS). In this study, we investigated whether the continuous administration of skin prophylaxis (10% urea, panthenol, bisabolol, vitamin A, C and E) is capable of protecting against capecitabine-induced HFS and allowing a more convenient oral therapeutic option. In this retrospective analysis, the toxicity profiles, according to NCI CTCAE 3.0 criteria, of 54 patients with gastrointestinal cancer who received either XELOX (34 patients) or FOLFOX-4 (20 patients) were compared using Fisher tests. The treatment protocols that were compared, herein, did not differ significantly in the majority of the analyzed items, with the exception of increased nausea (XELOX-70), fatigue (XELOX-130) and tumor pain . No significant differences were observed among the various groups with regard to emesis, diarrhea, mucositis, exanthema, alopecia, loss of weight and the incidence of infections. In particular, no significant differences in toxicity levels occurred in terms of dose, and HFS was limited if skin prophylaxis was performed continuously. XELOX-based palliative regimens provide an equally effective and comparably toxic therapeutic alternative to FOLFOX-4 if HFS prophylaxis is performed continuously.Since the oral administration of capecitabine is a more convenient method of application, it provides patients with a quality of life-preserving therapeutic alternative.

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Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study

Abstract: XELOX is noninferior to FOLFOX-4 when administered as second-line treatment in patients with metastatic colorectal cancer.

Cited by 172 publications

References 18 publications

Capecitabine plus oxaliplatin compared with 5-fluorouracil plus oxaliplatin in metastatic colorectal cancer: Meta-analysis of randomized controlled trials

Capecitabine plus oxaliplatin compared with 5-fluorouracil plus oxaliplatin in metastatic colorectal cancer: Meta-analysis of randomized controlled trials

Phase I trial of oxaliplatin plus S-1 chemotherapy in patients with metastatic colorectal cancer

Combination therapies with oxaliplatin and oral capecitabine or intravenous 5-FU show similar toxicity profiles in gastrointestinal carcinoma patients if hand-food syndrome prophylaxis is performed continuously

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