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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ABSTRACT: Die Behandlung des metastasierten kolorektalen Karzinoms (KRK) hat sich in den letzten Jahren entscheidend gewandelt und wird zunehmend zur individualisierten Therapie. Seit wenigen Jahren stehen neben einer Reihe von hochwirksamen Chemotherapeutika monoklonale Antikörper für die Behandlung zur Verfügung. Mittlerweile hängt die Entscheidung über die Art und Dauer der Therapie stark davon ab, welches Ausmaß die Erkrankung hat und ob der Patient symptomatisch ist. Auch das Vorliegen bestimmter genetischer Veränderungen beeinflusst die Wahl der Substanz. Therapieziel in der palliativen Situation bleibt die Verlängerung des Überlebens und eine Verbesserung der Lebensqualität. Bei der Patientengruppe, die primär nicht resektable Lebermetastasen aufweist, die durch Verkleinerung resezierbar werden können, kann durch eine intensive neoadjuvante Therapie sekundär die Möglichkeit der chirurgischen Entfernung der Tumormanifestationen herbeigeführt und die Patienten können so potenziell geheilt werden. Treatment of advanced colorectal carcinoma (aCRC) has changed considerably over the past few years and is becoming increasingly individualized. In addition to highly effective chemotherapeutics, monoclonal antibodies became available for treating CRC a few years ago. The decision as to the type and duration of treatment now heavily depends on the extent of the disease and whether the patient is symptomatic. The existence of certain genetic changes also affects the choice of substance. The aim of palliative treatment remains to extend the patient’s life and to improve quality of life. In a patient group with primarily non-resectable liver metastases that may become resectable following a reduction in size, intensive neoadjuvant therapy can create the option of secondary surgical removal of the tumor manifestations and thus potentially cure the patients.Der Gastroenterologe 01/2008; 3(2):135-143.
Article: Colorectal cancer.[Show abstract] [Hide abstract]
ABSTRACT: Substantial progress has been made in colorectal cancer in the past decade. Screening, used to identify individuals at an early stage, has improved outcome. There is greater understanding of the genetic basis of inherited colorectal cancer and identification of patients at risk. Optimisation of surgery for patients with localised disease has had a major effect on survival at 5 years and 10 years. For rectal cancer, identification of patients at greatest risk of local failure is important in the selection of patients for preoperative chemoradiation, a strategy proven to improve outcomes in these patients. Stringent postoperative follow-up helps the early identification of potentially radically treatable oligometastatic disease and improves long-term survival. Treatment with adjuvant fluoropyrimidine for colon and rectal cancers further improves survival, more so in stage III than in stage II disease, and oxaliplatin-based combination chemotherapy is now routinely used for stage III disease, although efficacy must be carefully balanced against toxicity. In stage II disease, molecular markers such as microsatellite instability might help select patients for treatment. The integration of targeted treatments with conventional cytotoxic drugs has expanded the treatment of metastatic disease resulting in incremental survival gains. However, biomarker development is essential to aid selection of patients likely to respond to therapy, thereby rationalising treatments and improving outcomes.The Lancet 03/2010; 375(9719):1030-47. · 39.06 Impact Factor
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ABSTRACT: A patient is described who presented with an obstructive adenocarcinoma in the ascending colon and two liver metastases. She underwent right hemicolectomy with concurrent lymphadenectomy. As one of the liver metastases was considered irresectable, she received bevacizumab-containing chemotherapy. The disease responded well to treatment and after 4 months the largest lesion was subjected to radiofrequency ablation and the smaller could be removed. Eventually, systemic treatment was discontinued. At a later time-point the patient developed a new metastasis in the hilum of the liver. Bevacizumab-containing treatment was again successful; the patient experienced a complete response. Currently, she feels well. The only sign of disease is a slightly elevated carcino-embryonic antigen level at 36 months after diagnosis of metastatic colon cancer.Anti-cancer drugs 06/2011; 22 Suppl 2:S1-7. · 2.23 Impact Factor