Metronomic Antiangiogenic Therapy with Capecitabine and Celecoxib in Advanced Tumor Patients – Results of a Phase II Study

Steinbild, Simone; Arends, J.; Medinger, Michael; Häring, Brigitte; Frost, Annette; Drevs, Joachim; Unger, Clemens; Strecker, Ralph; Hennig, Jürgen; Mross, Klaus

doi:10.1159/000110580

Cited by 38 publications

(27 citation statements)

References 44 publications

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“…Our novel observation sheds light on the possible clinical use of metronomic chemotherapy in frail and previously untreated human patients (especially for the low toxicity profile of our schedule) and the possible relevance of the measurement of baseline plasma VEGF in human patients who are candidate to receive, in future clinical studies, a metronomic CTX plus CXB. Indeed, these two drugs have been already administered together in human metronomic chemotherapy schedules with promising results as recently published in prostate cancer, lymphomas and other cancers [26][27][28][29][30]. Interestingly, Calleri and colleagues [31] have suggested the use of VEGF as a biomarker for treatment selection in metastatic breast cancer patients, previously treated with two-three lines of standard chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

et al. 2011

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Metronomic chemotherapy—the low-dose, long term and\ud \ud frequently administered chemotherapy—has revealed in\ud \ud these years an important impact on the stabilization of\ud \ud cancer disease for its known antiangiogenic effects,\ud \ud prolonged clinical benefits and the improved quality of life\ud \ud of several cancer patients, without any high grade toxicity\ud \ud [1–3]. Both the low cost and the oral administration of the\ud \ud drugs are key characteristics of this schedule and may offer\ud \ud important social advantages [4]. Anecdotical case reports\ud \ud [5–7] and experiences in small subsets of patients enrolled\ud \ud in retrospective clinical studies [8–10] on metastatic cancers\ud \ud have been recently published about the use of metronomic\ud \ud therapy as a first-line treatment. These point out the\ud \ud possible importance of metronomic chemotherapy as an\ud \ud alternative approach to first-line therapy in frail patients\ud \ud requiring palliation or patients refusing the standard\ud \ud chemotherapy for its impact on the quality of life. However,\ud \ud no data of prospective clinical trials on first line metronomic\ud \ud chemotherapy are currently available in metastatic\ud \ud cancer human patients.\ud \ud The veterinary medical oncology has advanced dramatically\ud \ud over the past few decades, because of the successful\ud \ud application of a number of conventional chemotherapeutic\ud \ud drugs to the cancer conditions diagnosed in veterinary\ud \ud patients [11]. Veterinary oncology cases often present a\ud \ud unique opportunity to investigate novel drugs and treatment\ud \ud schedules providing many in vivo information to the larger\ud \ud medical community and giving new effective options for\ud \ud dogs themselves [12]. As well recently pointed out by\ud \ud Paoloni and Khanna [13], these studies may also have a\ud \ud great translational relevance, predicting new therapies and\ud \ud related surrogate markers in human beings because pet dogs\ud \ud with cancers might assist the transition between mouse\ud \ud models and human patients. Moreover, in the clinical\ud \ud practice, veterinarians and their clients are generally less\ud \ud willing to accept a high degree of side effects, which most\ud \ud often results in lower drug doses than the ones that are used\ud \ud in human oncology.\ud \ud The aim of the present pilot study was to test a first-line\ud \ud metronomic oral combination of cyclophosphamide (CTX)\ud \ud and celecoxib (CXB) in canine metastatic spontaneous\ud \ud tumours, characterizing possible biomarkers to translate in\ud \ud human clinical research

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Section: Discussionmentioning

confidence: 99%

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

et al. 2011

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“…A daily dose of 1300 mg/m 2 of MC showed both good tolerability and efficacy in patients with advanced breast cancer [25]. A dose of capecitabine of 500 mg twice daily was shown to have activity and antiangiogenic effectiveness in colorectal cancer [26]. Also, a fixed daily dose of 1000 mg of MC was found to be safe and valid treatment option in advanced colorectal and gastric cancer patients [27].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Toxicity of Metronomic Capecitabine in Advanced Hepatocellular Carcinoma

Farrag¹

2012

JCT

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Background: Hepatocellular carcinoma (HCC) is a hypervascular tumor. Metronomic chemotherapy; the continuous administration of low-dose chemotherapy; has both cytotoxic and antiangiogenic effects with low toxicity profile. We evaluated the efficacy and toxicity of metronomic capecitabine (MC) in patients with advanced HCC. Patients and Methods: From May 2010, we enrolled pts with either metastatic or locally advanced diseases not candidate for ablative or locoregional treatment and have acceptable liver function. Patients received oral MC in dose of 1000 mg/m 2 daily in a 21 days cycle without interruption till disease progression or toxicity. Results: The study cohort consisted of 22 patients with a median age of 63 years. The median number of cycles received was 3 cycles (range 1 -9). From 19 patients were evaluable for response we had 3 partial responders, 10 stable diseases and disease progression in 6 patients. Median time to progression (TTP) was 2.2 months (95% CI 1.4 -6.24) and median survival time (OS) was 4.8 months (95% CI 1.8 -7.9). For 20 patients evaluable for safety: no grade III/IV hematological toxic effects were observed. Non-hematological toxic effects included grade III vomiting and diarrhea in one patient and grade III hand-foot syndrome in one patient. There was no treatment-related mortality. Conclusions: Based on the observed response rate, TTP and OS; MC has a modest antitumor efficacy in pts with advanced HCC. However, due to its low toxicity profile it deserves further attention as a convenient, outpatient-based chemotherapy regimen.

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“…Studies that have defined "nonprogression" as an endpoint have shown that K trans reduction discriminated between patients with progressive disease (no significant or minimal early pharmacodynamic change in K trans ) and those without progressive disease (significant pharmacodynamic change in K trans ; refs. [69][70][71][72]. Similar approaches were implemented in phase I and II trials of more homogeneous patient groups including vatalanib in mCRC (73) and bevacizumab in inflammatory breast cancer (74).…”

Section: Current Evidence In Mixed (Phase I) Patient Populationsmentioning

confidence: 99%

Do Imaging Biomarkers Relate to Outcome in Patients Treated with VEGF Inhibitors?

O’Connor

Jayson

2012

Clinical Cancer Research

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The management of solid tumors has been transformed by the advent of VEGF pathway inhibitors. Early clinical evaluation of these drugs has used pharmacodynamic biomarkers derived from advanced imaging such as dynamic MRI, computed tomography (CT), and ultrasound to establish proof of principle. We have reviewed published studies that used these imaging techniques to determine whether the same biomarkers relate to survival in renal, hepatocellular, and brain tumors in patients treated with VEGF inhibitors. Data show that in renal cancer, pretreatment measurements of K trans and early pharmacodynamic reduction in tumor enhancement and density have prognostic significance in patients treated with VEGF inhibitors. A weaker, but significant, relationship is seen with subtle early size change (10% in one dimension) and survival. Data from high-grade glioma suggest that pretreatment fractional blood volume and K trans were prognostic of overall survival. However, lack of control data with other therapies prevents assessment of the predictive nature of these biomarkers, and such studies are urgently required.

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Metronomic Antiangiogenic Therapy with Capecitabine and Celecoxib in Advanced Tumor Patients – Results of a Phase II Study

Cited by 38 publications

References 44 publications

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

Efficacy and Toxicity of Metronomic Capecitabine in Advanced Hepatocellular Carcinoma

Do Imaging Biomarkers Relate to Outcome in Patients Treated with VEGF Inhibitors?

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