Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Leucovorin Plus Oxaliplatin in Metastatic Colorectal Cancer: A Final Report of the AIO Colorectal Study Group
ABSTRACT To compare the use of capecitabine plus oxaliplatin (CAPOX) with infusional fluorouracil (FU)/folinic acid plus oxaliplatin (FUFOX) as first-line therapy for patients with metastatic colorectal cancer (MCRC).
A total of 474 patients with MCRC received either CAPOX (capecitabine 1,000 mg/m2 bid, days 1 to 14 plus oxaliplatin 70 mg/m2 days 1 and 8, repeated every 22 days) ) or FUFOX (oxaliplatin 50 mg/m2 followed by leucovorin 500 mg/m2 plus FU 2,000 mg/m2 as a 22-hour infusion days 1, 8, 15, and 22, repeated every 36 days). The primary end point was progression-free survival (PFS). Secondary end points were response rate (RR), overall survival (OS), time to treatment failure, and toxicity. The study was designed to determine noninferiority for the CAPOX regimen.
Median PFS was 7.1 months in the CAPOX arm and 8.0 months in the FUFOX arm (hazard ratio [HR], 1.17; 95% CI, 0.96 to 1.43; P = .117). Median OS was 16.8 months (CAPOX) and 18.8 months (FUFOX; HR, 1.12; 95% CI, 0.92 to 1.38; P = .26). Overall RRs were 48% for CAPOX (95% CI, 41% to 54%) and 54% for FUFOX (95% CI, 47% to 60%). Both regimens were generally well tolerated, although there was a significantly higher incidence of grade 2/3 hand-foot syndrome (HFS) in the CAPOX arm (P = .028).
CAPOX resulted in a slightly inferior efficacy than FUFOX. With respect to PFS, the best estimate of the HR of 1.17 was within the prespecified equivalence range. However, a relevant inferiority cannot be excluded. Both regimens were generally well tolerated but there was a significantly higher rate of grade 2/3 HFS in the CAPOX arm.
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- "It was approved by US Food And Drug Administration (FDA) in 2004, based on the AVF2107 study  comparing bolus irinotecan, 5 fluorouracil, leucovorin (IFL), and placebo therapy with IFL and bevacizumab showed a 4.7 and 4.4 month increase in median OS and PFS, respectively. However, FOLFOX, FOLFIRI [4, 5], and XELOX [6–8] became standard first-line therapy for mCRC now. Comparing FOLFOX regimen, IFL showed more early deaths, greater toxicity, and worse effectiveness in N9741 study . "
ABSTRACT: Background. Efficacy of adding bevacizumab in first-line chemotherapy of metastatic colorectal cancer (mCRC) has been controversial. The aim of this study is to gather current data to analyze efficacy of adding bevacizumab to the most used combination first-line chemotherapy in mCRC, based on the 2012 meta-analysis reported by Macedo et al. Methods. Medline, EMBASE and Cochrane library, meeting presentations and abstracts were searched. Eligible studies were randomized controlled trials (RCTs) which evaluated first-line chemotherapy with or without bevacizumab in mCRC. The extracting data were included and examined in the meta-analysis according to the type of chemotherapy regimen. Results. Seven trials, totaling 3436 patients, were analyzed. Compared with first-line chemothery alone, the adding of bevacizumab did not show clinical benefit for OS both in first-line therapy and the most used combination chemotherapy (HR = 0.89; 95% CI = 0.78-1.02; P = 0.08; HR = 0.93; 95% CI = 0.83-1.05; P = 0.24). In contrast with OS, the addition of bevacizumab resulted in significant improvement for PFS (HR = 0.68; 95% CI = 0.59-0.78; P < 0.00001). Moreover, it also demonstrated statistical benefit for PFS in the most used combination first-line chemotherapy (HR = 0.84; 95% CI = 0.75-0.94; P = 0.002). And the subgroup analysis indicated only capacitabine-based regimens were beneficial. Conclusions. This meta-analysis shows that the addition of bevacizumab to FOLFOX/FOLFIRI/XELOX regimens might not be beneficial in terms of OS. Benefit has been seen when PFS has been taken into account. In subgroup analysis, benefit adding bevacizumab has been seen when capecitabine-based regimens are used. Further studies are warranted to explore the combination with bevacizumab.Gastroenterology Research and Practice 05/2014; 2014(1):594930. DOI:10.1155/2014/594930 · 1.75 Impact Factor
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- "This fact is well-demonstrated from clinical trials indicating the low median survival of patients diagnosed with peritoneal carcinomatosis . Current treatment of peritoneal carcinomatosis involves removing the majority of peritoneal metastases (cytoreductive surgery) followed by intravenous (IV) administration of chemotherapeutic agents such as oxaliplatin in combination with 5-fluorouracil or leucovorin   to kill remaining tumor cells. Also platinum-based (i.e. "
ABSTRACT: Intraperitoneal (IP) administration of nano-sized delivery vehicles containing small interfering RNA (siRNA) is recently gaining attention as an alternative route for the efficient treatment of peritoneal carcinomatosis. The colloidal stability of nanomatter following IP administration has, however, not been thoroughly investigated yet. Here, enabled by advanced microscopy methods such as Single Particle Tracking (SPT) and Fluorescence Correlation Spectroscopy (FCS), we follow the aggregation and cargo release of nano-scaled systems directly in peritoneal fluids from healthy mice and ascites fluid from a patient diagnosed with peritoneal carcinomatosis. The colloidal stability in the peritoneal fluids was systematically studied in function of the charge (positive or negative) and Poly-Ethylene Glycol (PEG) degree of liposomes and polystyrene nanoparticles, and compared to human serum. Our data demonstrate strong aggregation of cationic and anionic nanoparticles in the peritoneal fluids, while only slight aggregation was observed for the PEGylated ones. PEGylated liposomes, however, lead to a fast and premature release of siRNA cargo in the peritoneal fluids. Based on our observations, we reflect on how to tailor improved delivery systems for IP therapy.Acta biomaterialia 03/2014; 10(7). DOI:10.1016/j.actbio.2014.03.012 · 5.68 Impact Factor
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- "However, no prospective trials of cisplatin-containing chemotherapy for NETs have previously been undertaken. Over the last 10 years, capecitabine (Cap) has been effectively substituted for 5-FU in many regimens used to treat gastrointestinal tract cancers   . Cap has reported activity as a single agent or in combination regimens for non-pancreatic NETs   as well as in combination with temozolomide for pancreatic NETs . "
ABSTRACT: Cytotoxic chemotherapy is widely used for advanced, unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and the most commonly used regimen combines 5-fluorouracil with streptozocin. The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin. Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625mg/m(2) twice daily orally, streptozocin (Strep) 1.0g/m(2) intravenously on day 1, with or without cisplatin (Cis) 70mg/m(2) intravenously on day 1. The primary outcome measure was objective response. Secondary outcome measures included progression-free and overall survival, quality of life, toxicity and biochemical response. 86 (44 CapStrep, 42 CapStrepCis) patients were randomised. Best objective response rate was 12% (95% confidence interval (CI)=2-22%) with CapStrep and 16% (95% CI=4-27.4%) with CapStrepCis. Disease-control rate was 80% with CapStrep and 74% with CapStrepCis. The estimated median progression-free and overall survival were 10.2 and 26.7months for CapStrep and 9.7 and 27.5months for CapStrepCis. 44% of CapStrep and 68% of CapStrepCis patients experienced grade ⩾3 adverse events. The efficacies of the novel CapStrep±Cis regimens were very similar. CapStrep was better tolerated than CapStrepCis. The trial was registered as EudraCT: 2004-005202-71 and ISRCTN: 35124268.European journal of cancer (Oxford, England: 1990) 01/2014; 50(5). DOI:10.1016/j.ejca.2013.12.011 · 4.82 Impact Factor