Lower incidence of adverse events about capecitabine and oxaliplatin from the GOIM 2802 study: a commentary (original) (raw)
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International Journal of Cancer, 2011
A regimen consisting of 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) is widely used in France in the first-line treatment of metastatic colorectal cancer (MCRC). The aim of our study was to demonstrate the non-inferiority of capecitabine plus oxaliplatin (XELOX) versus FOLFOX-6 for this indication. Patients were randomly assigned to receive XELOX or FOLFOX-6 for 6 months. The primary endpoint was overall response rate (ORR) in the per-protocol (PP) population; however, progression-free and overall survival (OS), time to response and response duration were also assessed. A total of 306 patients were enrolled (XELOX n 5 156; FOLFOX-6 n 5 150). ORR was 42 and 46% with XELOX and FOLFOX-6, respectively, in the PP population. The difference between groups was 4.7%; the upper limit of the unilateral 95% confidence interval (14.4%) was below the non-inferiority margin of 15%. In the intent-to-treat population, median progression-free survival was 8.8 months with XELOX and 9.3 months with FOLFOX-6, and median OS was 19.9 and 20.5 months, respectively. XELOX patients had significantly more grade 3/4 thrombocytopenia (12% vs. 5%) and diarrhoea (14% vs. 7%), but significantly less grade 3/4
Journal of Clinical Oncology, 2004
Purpose Capecitabine has demonstrated high efficacy as first-line treatment for metastatic colorectal cancer (MCRC). Oxaliplatin shows synergy with fluorouracil (FU), with little toxicity overlap. The XELOX regimen (capecitabine plus oxaliplatin), established in a previous dose-finding study, should improve on infused oxaliplatin with FU and leucovorin (FOLFOX) regimens. The present studies further characterize efficacy and safety of the XELOX regimen. Patients and Methods The antitumor activity of XELOX was investigated in a colon cancer xenograft model. Patients with MCRC received first-line XELOX in 3-week treatment cycles: intravenous oxaliplatin 130 mg/m2 (day 1) followed by oral capecitabine 1,000 mg/m2 twice daily (day 1, evening, to day 15, morning). Results A preclinical study confirmed that capecitabine has supra-additive activity with oxaliplatin. In the clinical study, 53 of 96 patients (55%) achieved an objective response, and 30 (31%) experienced disease stabilization ...
Clinical Colorectal Cancer, 2006
Replacing infusional 5-fluorouracil (5-FU)/leucovorin (LV) with oral capecitabine would be more convenient to patients, because it would lead to reduced hospital chair time and infusion-related toxicities. Previous trials with oral capecitabine-based regimens (other than XELOX [capecitabine/ oxaliplatin]) have failed to demonstrate the equivalent efficacy of capecitabinebased regimens to various 5-FU/oxaliplatin regimens (nonstandard FOLFOX [5-FU/LV/oxaliplatin] combinations); of note, these trials did not use the XELOX and standard FOLFOX regimens. An international phase III trial (NO16966) was initiated to demonstrate the noninferiority of XELOX to FOLFOX4 for the first-line treatment of metastatic colorectal cancer. The protocol was later amended to compare bevacizumab and chemotherapy versus placebo and chemotherapy. The efficacy data showed that XELOX was as effective as FOLFOX4 (progression-free survival [PFS; intent-to-treat population]: hazard ratio [HR], 1.04; 97.5% confidence interval, 0.93-1.16). Also, bevacizumab/chemotherapy (pooled with XELOX or FOLFOX) significantly prolonged PFS (HR, 0.83; P = 0.0023) compared with placebo and chemotherapy (XELOX/FOLFOX). In subgroup analysis, the addition of bevacizumab to XELOX (9.3 months vs. 7.4 months; HR, 0.77; P = 0.0026) and FOLFOX4 (9.4 months vs. 8.6 months; HR, 0.89; P = 0.1871) prolonged PFS compared with respective placebo arms; however, it did not show statistical significance with the FOLFOX4 regimen. The adverse events were manageable and comparable between treatment arms.
Annals of Oncology, 2005
The efficacy of oxaliplatin combined with capecitabine (XELOX) as second-line therapy in patients with advanced colorectal cancer (ACRC) resistant to irinotecan is not well established. Oxaliplatin induces acute, cold-induced neuropathy in most patients. The incidence is claimed to be infusion rate-dependent and therefore a 2-h infusion is recommended. Patients and methods: For practical and economic reasons, but also for patient's convenience, we performed a phase II study to examine XELOX 30 (capecitabine 1000 mg/m 2 orally twice daily on days 1-14 and oxaliplatin 130 mg/m 2 as a 30 min infusion on day 1) in patients with ACRC resistant to irinotecan. In addition the pharmacokinetics of oxaliplatin was studied. Results: From November 2002 to September 2003, 70 patients with ACRC were treated with XELOX 30. Median age was 62 (range 33-74 years) years and median performance status was 1 (range 0-2). The median number of courses was four (range 1-12) and median cumulative dose of oxaliplatin was 530 (range 125-1560) mg/m 2. The response rate was 17% (95% CI 10-23), median time to progression (TTP) was 5.4 months (95% CI 4.6-6.4) and median survival 9.5 months (95% CI 8.5-11.2). White blood cell count (WBC) and performance status were significantly correlated to TTP. Neurotoxicity was moderate: grade 1 56%, grade 2 17% and grade 3 6%. Other grade 3 toxicities were nausea/vomiting 9%, diarrhoea 14% and PPE 8%. The maximum blood concentration and total body clearance of oxaliplatin was higher than previously reported in studies examining 2-h infusions, but the volume of distribution and terminal half-life was in close agreement with previous results. Conclusion: XELOX 30 is a very convenient second-line regimen in ACRC with an activity and safety profile similar to other oxaliplatin schedules.
Jurnal Kedokteran dan Kesehatan Indonesia, 2009
Background: Combinations of Fluorouracil (FU) and biomodulator Leucovorin (LV) established as a standard regimen for therapy of colorectal cancer with metastases. To give better antitumor activity in colorectal cancer therapy, oxaliplatin is combined with FU/LV and give significant improvement. Fluorouracil can only be given by intravenous administration. This limitation raised effort to find alternative drugs that can be given orally, such as capecitabine. Capecitabine is an oral FU prodrug, with high oral bioavailability, highly accumulated in neoplastic tissue to be converted in FU, and well tolerated. Some clinical studies revealed effectivity of capecitabine plus oxaliplatin (XELOX) compared to FU/LV plus oxaliplatin (FOLFOX). Objective: This article is aimed to compare non inferiority of XELOX to FOLFOX in colorectal cancer with metastases, viewed form primary outcomes and secondary outcomes. Results: XELOX was comparable to FOLFOX with some benefitsover FOLFOX. Conclusion: XELOX could be considered as FOLFOX replacement as a standard therapyfor colorectal cancer with metastases. Latar Belakang: Sampai saat ini, terapi untuk kanker kolorektal masih didominasi oleh penggunaan fluorouracil (FU) yang dikombinasi dengan biomodulator leucovorin (LV). Penggunaan FU/LV seringkali dikombinasikan dengan oxaliplatinuntuk meningkatkan aktivitas antitumornya serta mencegah metastasis. Keterbatasan FU adalah hanya bisa diberikan secara intravena sehingga menyebabkan digalinya alternatif obat secara oral, salah satunya capecitabine. Capecitabine adalah prodrug bagi FU yang mempunyai bioavailabilitas oral tinggi, terkonsentrasi dalam jumlah besar dalam jaringan tumor untuk dikonversi menjadi FU, serta dapat ditoleransi dengan baik. Beberapa penelitian klinis telah menguji efektivitas penggunaan capecitabine plus oxaliplatin (XELOX) dibandingkan FU/LV plus oxaliplatin (FOLFOX). Tujuan: Tulisan ini bertujuan untuk membandingkan efek penggunaan kombinasi XELOX dibandingkan FOLFOX dalam terapi kanker kolorektal dengan metastasis yang ditinjau dari beberapa penelitian klinis, dengan melihat outcome primer dan sekundernya. Hasil: Hasil menunjukkan bahwa penggunaan XELOX non inferior dari FOLFOX pada kanker kolorektal dengan metastasis, yang dilihat darioutcome primer dan outcome sekunder, serta memberikan beberapa Review Article 188 Miladiyah. Analysis of capecitabine plus oxaliplatin... kelebihan dibandingkan dengan FOLFOX Kesimpulan: XELOX dapat dipertimbangkan sebagai regimen pengganti FOLFOX untuk terapi kanker kolorektal dengan metastasis.