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.
- SourceAvailable from: Sacha Satram-Hoang[show abstract] [hide abstract]
ABSTRACT: PURPOSE: Treatment advances have improved outcomes in clinical trials of patients with metastatic colorectal cancer (mCRC). Less is known about these effects for patients in real-world settings. This study evaluated treatment patterns and survival in older, demographically diverse patients with mCRC. METHODS: A retrospective cohort analysis was performed for 4,250 patients from January 1, 2000 to December 31, 2007 using linked Surveillance, Epidemiology, and End Results-Medicare database. Patients were ≥66 years, enrolled in Medicare parts A and B, and received first-line treatment with fluorouracil and leucovorin (5-FU/LV), capecitabine (CAP), 5-FU/LV plus oxaliplatin (FOLFOX), or CAP and oxaliplatin (CAPOX). Cox regression with backward elimination and propensity score-weighted Cox regression estimated relative risk of death. Date of last follow-up was December 2009. Statistical comparisons were made between 5-FU/LV vs. CAP and FOLFOX vs. CAPOX. RESULTS: Compared to 5-FU/LV, patients treated with CAP were older (mean age 78 vs. 76; P < 0.0001) and more likely female (61 vs. 54 %; P = 0.0017), while patients receiving CAPOX and FOLFOX were similar in age (mean age 74 vs. 73; P = 0.0924). Complications requiring medical resource utilization following initiation of therapy were significantly higher among patients administered with 5-FU/LV (54 %) vs. CAP (17 %; P < 0.0001) and FOLFOX (75 %) vs. CAPOX (57 %; P < 0.0001). The multivariate analysis revealed no significant differences in survival between 5-FU/LV and CAP and between FOLFOX and CAPOX. CONCLUSIONS: Overall survival was comparable between CAP and 5-FU/LV and between CAPOX and FOLFOX with fewer complications requiring medical resource utilization associated with CAP and CAPOX, thus confirming clinical trial results.Journal of Gastrointestinal Cancer 11/2012;
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ABSTRACT: Intraperitoneal (IP) chemotherapy is an effective way of treating peritoneal carcinomatosis of colorectal origin after complete cytoreduction. Although IP therapy has been already performed for many years, no standardized treatment design has been developed in terms of schedule, residence time, drug, or carrier solution. Because of the fast clearance of the conventional intravenous (IV) drug delivery systems used for IP therapy, a lot of research is performed to optimize IP drug delivery and extend the residence time of the cytotoxic agent in the peritoneal cavity. This paper reviews the recent advances made in drug delivery systems for IP chemotherapy, discussing the use of microparticles, nanoparticles, liposomes, micelles, implants, and injectable depots for IP delivery.TheScientificWorldJOURNAL 01/2013; 2013:720858. · 1.73 Impact Factor
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ABSTRACT: Despite more than 70 years of research concerning medication for cancer treatment, the disease still remains one of the leading causes of mortality worldwide. Many cancer types lead to death within a period of months to years. The original class of chemotherapeutics is not selective for tumor cells and often has limited efficacy, while treated patients suffer from adverse side‑effects. To date, the concept of tumor‑specific targeted therapy drugs has not fulfilled its expectation to provide a key for a cure. Today, many oncology trials are designed using a combination of chemotherapeutics with targeted therapy drugs. However, these approaches have limited outcomes in most cancer indications. This perspective review provides a rationale to combine targeted therapy drugs for cancer treatment based on observations of evolutionary principles of tumor development and HIV infections. In both diseases, the mechanisms of immune evasion and drug resistance can be compared to some extent. However, only for HIV is a breakthrough treatment available, which is the highly active antiretroviral therapy (HAART). The principles of HAART and recent findings from cancer research were employed to construct a hypothetical model for cancer treatment with a multi‑drug regimen of targeted therapy drugs. As an example of this hypothesis, it is proposed to combine already marketed targeted therapy drugs against VEGFRs, EGFR, CXCR4 and COX2 in an oncology trial for non‑small cell lung cancer patients without further treatment options.Oncology Reports 07/2013; · 2.30 Impact Factor