Low-dose Metronomic Capecitabine (Xeloda) for Treatment of Metastatic Gastrointestinal Cancer: A Clinical Study

Abstract

Background: Metastatic gastrointestinal cancer (GI-cancer) is often a chronic disease where the treatment intention often is palliative. For such patients, it is important to offer treatments that can prevent tumor progression without reducing quality of life more than necessary. Metronomic chemotherapy involves continuous administration of cytostatic drugs at low doses without longer drugfree intervals. Capecitabine (Xeloda) is a prodrug, given in a tablet formulation, that is selectively converted to 5-Fluorouracil at the tumor sites. In this study, we aimed to explore the efficacy and tolerability of metronomic Xeloda.Methods: Patients (n = 87) diagnosed with a primary metastatic or recurrent disease were included and retrospectively analyzed. Clinical data were obtained from patient journals. All patients had been treated with metronomic Xeloda (500 mg × 2). Primary endpoints were to investigate the two-year overall survival (OS) and the best response. Best response was evaluated by radiological and clinical examination. Standard RECIST criteria were used. Survival analysis was performed using the Kaplan-Meier method.Results: Regress stable disease and progress were seen in 13% (n = 11), 38% (n = 33) and 47% (n = 41) of the cases respectively. The two-year OS for the cohort was 56% and median OS was 26 months. The treatment was well tolerable and all reported side effects (n = 21) were of toxicity grade I or II. Conclusions:Our data show that metronomic Xeloda may offer a therapeutic alternative for highly motivated patients in a good general condition when evidence-based regimens are not considered suitable or have failed.

Diffuse reflectance spectroscopy to monitor murine colorectal tumor progression and therapeutic response

“…In contrast, the concept of low-dose continuous (metronomic) chemotherapy has been developed over the past 15 years, as it minimizes treatment side effects while targeting the endothelial cells of the tumor vasculature, which are not allowed to recover. 12,13 This therapy has been explored as NAC in clinical studies of ovarian, cervical, and breast cancers, where tumor reduction was observed. [14][15][16] Novel administration strategies for CRC-with the intent of understanding the mechanistic effects of this approach, as well as to identify potential clinically viable (endoscopic) biomarkers of positive therapy response-require the use of in vivo, primary models of the disease.…”

Longitudinal examination of perfusion and angiogenesis markers in primary colorectal tumors shows distinct signatures for metronomic and maximum-tolerated dose strategies

“…The term “metronomic chemotherapy” was coined to describe chemotherapy that involves the use of lower but active doses of chemotherapeutic drugs without prolonged rest periods in between [14] . Early studies on metronomic chemotherapy (MET), showed that the targets of this type of treatment were the endothelial cells of the tumor, which could not recover due to the continuous delivery of the drugs 14 , 15 , which translated in an anti-angiogenic effect [16] .…”

Metronomic Low Dose Leucovorin- Fluorouracil versus Supportive Treatment for Patients with Recurrent or Metastatic Colorectal Cancer

“…There was an improvement in therapeutic regimens for advanced CRC in the last few decades. The low dose metronomic palliative chemotherapy in patients with advanced CRC after failure of standard chemotherapy led to a dramatic increase in efficacy, reduction of mortality rates, and improves survival in the form of control symptoms, and enhances or improves quality of life which is important issue in that group of patients [6,7].…”