New systemic frontline treatment for metastatic colorectal carcinoma

Braun, Ada; Achterrath, W.; Wilke, H.; Vanhoefer, U.; Harstrick, A.; Preusser, P.

doi:10.1002/cncr.20154

Cited by 66 publications

(42 citation statements)

References 112 publications

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“…Currently available treatment options for glioblastoma multiforme and colorectal cancer have made improvements in the quality-of-life for patients with these cancers; however, they are still limited in the overall objective response rates and survival benefit (2,6,9,13,14). Based on the highly vascularized nature of these tumors, novel therapeutic strategies employing antiangiogenic agents in combination with traditional cytotoxic agents are being evaluated for treating these cancers.…”

Section: Discussionmentioning

confidence: 99%

The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice

Jones‐Bolin

Zhao²,

Hunter³

et al. 2006

Molecular Cancer Therapeutics

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CEP-7055, a fully synthetic, orally active N,N-dimethylglycine ester of CEP-5214, a C3-(isopropylmethoxy) -fused pyrrolocarbazole with potent pan -vascular endothelial growth factor receptor (VEGFR) kinase inhibitory activity, has recently completed phase I clinical trials in cancer patients. These studies evaluated the antitumor efficacy of CEP-7055 using orthotopic models of glioblastoma and colon carcinoma in combination with temozolomide, and irinotecan and oxaliplatin, respectively, for their effects on primary and metastatic tumor burden and median survival. Chronic administration of CEP-7055 (23.8 mg/kg/dose) and temozolomide resulted in improvement of median survival of nude mice bearing orthotopic human glioblastoma xenografts compared with temozolomide alone (261 versus 192 days, respectively; P V 0.02). Reductions in neurologic dysfunction, brain edema, hemorrhage, and intratumoral microvessel density (CD34 staining) were observed in glioma-bearing mice receiving CEP-7055 alone, temozolomide alone, and the combination of CEP-7055 and temozolomide relative to vehicle and to temozolomide monotherapy. The administration of CEP-7055 in combination with irinotecan (20 mg/kg/dose i.p. Â 5 days), and to a lesser degree with oxaliplatin (10 mg/kg/dose i.v.), showed reductions on primary colon carcinoma and hepatic metastatic burden in the CT-26 tumor model relative to that achieved by irinotecan and oxaliplatin monotherapy. These data show the significant efficacy and tolerability of optimal efficacious doses of CEP-7055 when given in combination with temozolomide and irinotecan relative to monotherapy with these cytotoxic agents in preclinical orthotopic glioma and colon carcinoma models and lend support for the use of these treatment regimens in a clinical setting in patients with glioblastoma and colon carcinoma.

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Section: Discussionmentioning

confidence: 99%

The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice

Jones‐Bolin

Zhao²,

Hunter³

et al. 2006

Molecular Cancer Therapeutics

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“…Capecitabine a fluoropyrimidene carbamate rationally designed as orally administered is currently approved by the FDA (Food and Drug Administration) EMA (European Medicinal Agency) and COFEPRIS (Federal Commission against Sanitary Risks, Mexico) as adjuvant in patients with colon, colorectal [1][2][3], breast [4,5], ovarian [6,7] and pancreatic [8][9][10] cancer, in combination with other antineoplasic drugs. Capecitabine a prodrug is selectively activated by tumor cells to its cytotoxic moiety, 5-fluorouracil (5-FU), by thymidine phosphorylase, which is generally expressed at high levels in tumors [11,12].…”

Section: Introductionmentioning

confidence: 99%

Bioequivalence of Two Formulations (Innovator vs Generic) of Capecitabine in Patients with Cancer of Colon

Betzabe¹,

Manuel²,

Rafael³

et al. 2015

CRJ

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Abstract:Capecitabine is an orally administered chemotherapeutic agent used in the treatment of numerous cancers including colon, colorectal, ovarian, breast and pancreatic. Considering the importance of generic drugs in Health Care Systems, it is essential that its quality, safety and efficacy be compared with the corresponding innovator product. The objective of the study was to compare the pharmacokinetics and relative bioequivalence between two tablet (500 mg) formulations of capecitabine in Mexican patients with cancer of colon. The study was designed as open, prospective, randomized, two-way, crossover bioequivalence trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 24 patients. After each administration, serial blood samples were collected for up 8 hr. The washout between the two administrations was 3 days. Capecitabine was determined in plasma using LC/MS-MS. No statistically significant differences in C max , AUC 0-t , and AUC 0-α were found between the test and innovator formulations. Both products were well tolerated by the patients, with no serious adverse events. The generic capecitabine was pharmacokinetic bioequivalent with the innovator formulations.

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“…More recently, new chemotherapeutic drugs with different mechanisms of action such as irinotecan and oxaliplatin have been demonstrated to be active in combination with 5-FU. Therefore, 5FU-irinotecan or 5FU-oxaliplatin combinations have become the standard first-line regimens in metastatic CRC (Braun et al, 2004). Although there is clear evidence that chemotherapy in the first-line setting improves time to disease progression (TTP), overall survival (OS) and quality of life (QL), overall treatment results remain unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer

et al. 2007

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The recent successful development of monoclonal antibodies that target key components of biological pathways has expanded the armamentarium of treatment options for patients with colorectal cancer (CRC). In particular, the epidermal growth factor receptor (EGFR), a tyrosine kinase growth factor receptor involved in CRC development and progression, is exploited by the newest monoclonal antibody that is available for use in CRC patients. Cetuximab, the first chimeric monoclonal antibody, which has been generated against the EGFR, is currently registered in USA, Europe and worldwide, in combination with irinotecan in the treatment of metastatic CRC patients who have progressed on irinotecan containing chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of concomitant chemotherapy. Furthermore, a series of phase III clinical trials are currently evaluating the combination of cetuximab with standard chemotherapy regimens in the first-line treatment chemotherapy-naı¨ve patients with metastatic CRC.

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New systemic frontline treatment for metastatic colorectal carcinoma

Cited by 66 publications

References 112 publications

The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice

The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice

Bioequivalence of Two Formulations (Innovator vs Generic) of Capecitabine in Patients with Cancer of Colon

Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer

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