Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adjuvant therapy can reduce the risk of disease recurrence in patients with stage II-IV colorectal cancer. Recently, 3 monoclonal antibodies have been shown to improve clinical outcome in this group of patients. Bevacizumab is an antiangiogenesis agent that has been shown in clinical and preclinical models to reverse the effects of proangiogenic molecules. Bevacizumab is active in the adjuvant setting and in the treatment of metastatic disease. Cetuximab is targeted to the epidermal growth factor receptor. Panitumumab is a fully human immunoglobulin G2 antibody that also binds to the epidermal growth factor receptor. Combination therapies of monoclonal therapies and chemotherapy have resulted in better clinical outcomes than with either modality alone.
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PMID:Targeted therapy in colorectal cancer. 1731 96

On September 27, 2006, the U.S. Food and Drug Administration granted approval to panitumumab (Vectibix, Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Panitumumab approval is based on the results of a single, open-label, randomized, multinational study that enrolled 463 patients with EGFR-expressing (at least 1+ membrane staining in > or =1% of tumor cells) metastatic colorectal cancer. Patients were randomized to either best supportive care (BSC) alone or BSC plus panitumumab, 6 mg/kg i.v., every other week. The primary study endpoint was progression-free survival (PFS), determined by an independent review committee that was blinded as to treatment assignment. BSC patients who progressed were eligible to receive panitumumab. The study patients' median age was 62 years, with 40% aged > or =65; 63% were male, 99% were white, 86% had a baseline Eastern Cooperative Oncology Group performance status score of 0 or 1, and 67% had colon cancer. The median time from diagnosis of metastases was approximately 19 months and the median number of prior therapies was 2.4. The PFS duration was significantly longer among patients randomized to receive panitumumab in addition to BSC (n = 231) compared with BSC alone (n = 232). The median and mean PFS times were 56 and 96.4 days, respectively, for patients receiving panitumumab and 51 and 59.7 days, respectively, for patients receiving BSC alone. Nineteen partial responses (8%, 95% confidence interval [CI], 5.3%-12.5%) were observed in panitumumab treated patients. The median duration of response was 17 weeks (95% CI, 16-25 weeks). Approximately 75% of patients in the BSC alone arm crossed over to receive panitumumab after disease progression. There was no difference in overall survival between the two study arms. The most common adverse events were skin rash, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea. The most serious adverse events were pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, diarrhea, and constipation.
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PMID:FDA drug approval summary: panitumumab (Vectibix). 1752 46

Colorectal cancer is one of the leading causes of cancer-related death worldwide, with almost 20% of all patients presenting with metastatic disease at the time of their diagnosis. The treatment regimens and options of metastatic colorectal cancer have significantly changed in the last 10 years, leading to an improvement of response rates to about 50%, progression-free survival of about 10 months, and overall survival reaching over 2 years. Beside US Food and Drug Administration approval of the cytotoxic agents irinotecan (Camptosar), oxaliplatin (Eloxatin), and capecitabine (Xeloda), the increasing understanding of molecular pathways that comprise the cell cycle, apoptosis, angiogenesis, and invasion has provided novel targets in cancer therapy. The biologic agent bevacizumab (Avastin), an inhibitor against vascular endothelial growth factor, and cetuximab (Erbitux) and panitumumab (Vectibix), monoclonal antibodies to epidermal growth factor receptor, have demonstrated their efficacy in clinical trials. This article reviews the mechanisms of action and possible markers of resistance, and summarizes data on the clinical efficacy of targeting agents.
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PMID:Targeting metastatic colorectal cancer in 2008: a long way from 5-FU. 1847 17

The KRAS status is now a mandatory prerequisite in order to treat metastatic colorectal patients with anti-EGFR (epidermal growth factor receptor) antibodies, such as cetuximab (Erbitux) or panitumumab (Vectibix). KRAS mutations are unambiguously linked to a lack of response to these targeted therapies and to a poor outcome. The optimal determination of the KRAS status should be based on coordination between pathologists and biologists. The pathologist must morphologically check the tumor to be analyzed and be sure that the fixatives used are valuable for molecular biology. The pathologist's involvement may also concern the DNA extraction and the KRAS mutations analyses. This involvement has to be included in a multidisciplinary setting in order to get rapid and robust tests for the clinical use. The imperative knowledge of the KRAS status in the management of metastatic disease represents a good example of this multidisciplinary coordination. In the future, the pathologist's role should be extended, considering the emergence of a more and more personalized medicine, integrating efficiency and cost-effectiveness. Thus, the pathologist may contribute to validate new molecular tests and to offer his specific techniques for translational research.
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PMID:[Technical considerations for KRAS testing in colorectal cancer. The pathologist's point of view]. 2003 66

A 44-year-old female was referred to our hospital with a complaint of abdominal fullness. Computed tomography(CT) showed multiple liver masses and a huge ovarian tumor. Colonoscopy revealed a type 4 advanced cancer in the sigmoid colon. She was diagnosed with unresectable liver and ovarian metastases from advanced sigmoid colon cancer, for which we were obliged to select chemotherapy. As the first line, FOLFOX was applied and performed for 6 cycles, followed by FOLFOX plus bevacizumab(BV)for 5 cycles. While no deterioration of liver and ovarian metastases was observed during the course of those chemotherapy regimens, the patient developed a considerable level of acute sensorimotor neuropathic symptoms associated with oxaliplatin-induced peripheral neurotoxicity, forcing us to replace FOLFOX plus BV with FOLFIRI plus BV. Three cycles of FOLFIRI plus BV, however, turned out to be progressive disease with deterioration of liver and ovarian metastases. Since her oxaliplatin-induced neurotoxicity was improved, a regimen of FOLFOX plus BV was once again applied to her for 3 cycles, which failed to prevent her from having a progressive disease. The sequencing of K-RAS genes from the biopsy specimens of sigmoid colon cancer revealed an expression of a wild-type K-RAS. Thus, an addition of panitumumab to FOLFOX was made. Surprisingly, after 3 cycles of the chemotherapy regimen over 3 months, a significant reduction in the size of liver and ovarian metastases was observed. Her sense of abdominal fullness was apparently reduced and was even lower than what it was at admission. Panitumumab has great potential for effective treatment of patients with unresectable stage IV colorectal cancer, even after having acquired resistance to prior chemotherapy regimens.
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PMID:[A case of sigmoid colon cancer with liver and ovarian metastases effectively treated by panitumumab after acquiring resistance to prior chemotherapy regimens]. 2191 57

Panitumumab is a fully human monoclonal antibody targeting epidermal growth factor receptor (EGFR) approved for use in colorectal cancer (CRC). Critical information regarding biomarkers in CRC has been discovered through the investigation of panitumumab treatment. The discovery of anti-EGFR resistance in the setting of Kirsten rat sarcoma viral oncogene (KRAS) and more recently, neuroblastoma RAS viral oncogene (NRAS) mutations in CRC has changed the focus of therapy for metastatic disease to one based on the molecular characteristics of the tumor. This review will give a brief background on panitumumab and its current uses in CRC.
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PMID:Panitumumab in the treatment of colon cancer: A biomarker dilemma. 2537 66

29-year-old Hispanic woman presented to the clinic with complaints of abdominal pain, nausea, fatigue, and constipation. Laboratory tests indicated the presence of iron deficiency anemia and transaminitis. Imaging evaluation revealed marked hepatomegaly with multiple hepatic metastases and pelvic lymphadenopathy. Biopsy of the hepatic lesions showed adenocarcinoma positive for pan-cytokeratin, CMA5.2, villin, and CDX2. She was positive for tumor markers CA 19-9, CA-125, and CEA. Upon further evaluation, she was found to have colorectal cancer positive for KRAS and BRAF mutations. Unfortunately, her disease progressed rapidly and she expired within 3 months from the time of her first diagnosis. KRAS and BRAF mutations are rare enough to be considered virtually mutually exclusive but coexistent mutations appear to be a distinct molecular and clinical subset with aggressive course of illness, which is in dire need of new treatment strategies. Panitumumab and Cetuximab are approved for patients with wild type KRAS CRC. Vemurafenib is a potent inhibitor of the kinase domain in mutant BRAF and its use in BRAF mutated colon cancer remains to be well established. Our report highlights the need to obtain tissue samples from these patients for analysis and to evaluate the benefit of Vemurafenib in colorectal cancers.
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PMID:Are All Mutations the Same? A Rare Case Report of Coexisting Mutually Exclusive KRAS and BRAF Mutations in a Patient with Metastatic Colon Adenocarcinoma. 2881 46