Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Phase I clinical trial of 1-beta-D-arabinofuranosyl-5-azacytosine (ara-AC or fazarabine) given as a 72-h continuous infusion on a 21-day cycle was conducted in 27 adult patients with refractory cancer. The major toxicity was reversible granulocytopenia and thrombocytopenia. Dose-limiting toxicity was observed at a dose rate of 1.96 mg/m2/h in which Grade IV leukopenia (WBC less than 1,000/mm3) occurred in 4 of 11 patients and Grade IV thrombocytopenia (platelets less than 25,000/mm3) occurred in 3 of 11 patients. Plasma steady-state levels ranged from 0.13 to 0.6 microM for doses of 1.25 to 5.94 mg/m2/h. Mean total body clearance was 647 ml/min/m2. Minor clinical responses were seen in one patient with testicular cancer, one patient with colon cancer, one patient with breast cancer, and one patient with acute nonlymphocytic leukemia. Another patient with adenocarcinoma of unknown primary had stable disease during 13 cycles of therapy. Based on the results of this study, the recommended dose for Phase II studies of 1-beta-D-arabinofuranosyl-5-azacytosine administered as a 72-h continuous infusion is 2.0 mg/m2/h (48 mg/m2/day).
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PMID:Phase I and pharmacokinetic study of arabinofuranosyl-5-azacytosine (fazarabine, NSC 281272). 168 36

rTNF was administered to 28 patients with advanced metastatic cancers by continuous intravenous infusion for 5 consecutive days every 2 weeks. The dose levels were 30, 40, 70, 110, 180 and 290 micrograms/M2/day. Groups of 3 patients were started at each successive dose level and then on subsequent courses treated with the next dose level through 4 escalations as tolerated. Tumor types were: colon cancer 14; adenocarcinoma of unknown primary, 2; renal cancer, 2; leiomyosarcoma, 2; lung cancer, 1; prostate cancer, 1; thymona, 1; bladder cancer; 1; parotid, 1; Kaposi's sarcoma 2; ovarian 1. Toxicities included fever and chills (usually within the first 8 hours of infusion), fatigue, headache, decreased performance status, hypotension and CNS. All patients experienced leukopenia and thrombocytopenia within 24 hours or less after start of infusion with return of baseline by 72 hours after rTNF was stopped. The fall in these counts averaged 50% and was not dose related. No major changes in liver or renal function, coagulation or blood lipids were seen. Major dose limiting toxicities were fatigue, confusion, thrombocytopenia, seizures, hypotension and decreased performance status. NK cell activity measured against K562 target cells was augmented from about 30% target cell lysis to about 70% target cell lysis over the first 7 days of treatment. Two patients, both with metastatic colon cancer showed transient, objective tumor regression which did not qualify as a partial response. One patient with ovarian cancer had a stable partial response but progressed after 13 courses of treatment. Continuous infusion of TNF can be safely administered to patients with a maximum tolerated dose of only between 30 and 40 micrograms/M2/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I trial of recombinant tumor necrosis factor (rTNF) administered by continuous intravenous infusion in patients with disseminated malignancy. 264 24

Microangiopathic hemolytic anemia and thrombocytopenia secondary to disseminated intravascular coagulation is a well-described complication of widely metastatic carcinoma. The authors report four cases of gastric carcinoma, one case of colon cancer, and one case of adenocarcinoma of unknown primary in which the patient developed a syndrome analogous to thrombotic thrombocytopenic purpura, consisting of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure without definite evidence of disseminated intravascular coagulation. In contrast to previous reports, postmortem examination in three of the cases revealed no recurrence or only microscopic foci of residual tumor. In the remaining three, there was clinical and pathologic evidence of grossly disseminated carcinoma. Also in contrast to previous cases, all patients evidenced azotemia and proteinuria at the onset of the syndrome and ultimately uremia was a contributing cause of death. Coagulation profiles showed prolonged thrombin times and elevated fibrin degradation products in four instances and did not distinguish the patients with grossly metastatic disease from those with no tumor or only microscopic residua. Circulating immune complexes containing carcinoembryonic antigen were found in the patient with metastatic colon carcinoma. The syndrome was clinically identical whether or not grossly metastatic tumor was present, and it should not be attributed to advanced disease without definite clinical or pathologic evidence of a recurrence.
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PMID:Microangiopathic hemolytic anemia, thrombocytopenia, and renal failure in patients treated for adenocarcinoma. 728 73

Recently, MET exon 14 deletion (METex14del) has been postulated to be one potential mechanism for MET protein overexpression. We screened for the presence of METex14del transcript by multiplexed fusion transcript analysis using nCounter assay followed by confirmation with quantitative reverse transcription PCR with correlation to MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). We extracted RNAs from 230 patients enrolled onto the prospective molecular profiling clinical trial (NEXT-1) (NCT02141152) between November 2013 and August 2014. Thirteen METex14del cases were identified including 3 gastric cancer, 4 colon cancer, 5 non-small cell lung cancer, and one adenocarcinoma of unknown primary. Of these 13 METex14del cases, 11 were MET IHC 3+ and 2 were 2+. Only one out of the 13 METex14del cases was MET amplified (MET/CEP ratio > 2.0). Growths of two (gastric, colon) METex14del+ patient tumor derived cell lines were profoundly inhibited by both MET tyrosine kinase inhibitors and a monoclonal antibody targeting MET. In conclusion, METex14del is a unique molecular aberration present in gastrointestinal (GI) malignancies corresponding with overexpression of MET protein but rarely with MET amplification. Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies.
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PMID:Gastrointestinal malignancies harbor actionable MET exon 14 deletions. 2637 39

Oncology guidelines currently recommend against performing colonoscopies in the workup of adenocarcinoma of unknown primary unless colonic malignancy is otherwise suggested by clinical signs or symptoms. We present 2 cases of metastatic colonic adenocarcinoma that presented only with neurologic symptoms from vertebral metastasis. Although bony metastases are a rare presentation of colon cancer and colonoscopy is not warranted in the initial workup of adenocarcinoma of unknown primary, we describe these cases as a reminder that bony metastases do not rule out a colon cancer diagnosis.
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PMID:Vertebral Metastasis as the Initial Manifestation of Colon Cancer. 2780 74