Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen previously treated (with only one prior regimen) patients with histologically proven metastatic or locally recurrent colorectal carcinoma were treated with recombinant tumor necrosis factor (rTNF) administered by 30-minute i.v. infusions twice daily for 5 consecutive days every other week for 8 weeks. Patients received 100 micrograms/m2 twice daily on day 1 of cycle 1 with escalation to 150 micrograms/m2 twice daily thereafter. Patients were concomitantly treated with indomethacin 25 mg every 6 hours and acetaminophen 650 mg every 4 hours to obviate fever and chills. Toxicities included: nausea/vomiting (69%), headache (25%), chills (69%), pain at tumor sites (63%), hypotension (31%), and hypertension (38%). Hematologic toxicity included leukopenia less than 2000 cells/mm3 (38%) and thrombocytopenia less than 100,000 cells/mm3 (13%). Liver function abnormalities occurred independently of the site or extent of metastatic disease and inconsistently in each treatment cycle. Four patients developed bilirubinemia greater than 2.5 x baseline values (range, 2.5 to 10.3 U/L); five patients had greater than 2.5 x elevations in alkaline phosphatase (range, 624 to 1663 U/L). Two patients developed retinal vein thrombosis in the absence of hemostatic abnormalities. In both instances, this complication occurred several weeks after completion of therapy. No objective responses were noted in 14 evaluable patients (95% confidence interval: 0 to 0.23). Three patients had stable disease for a median duration of 4.5 months. In conclusion, i.v. rTNF at this dose and schedule has no demonstrable antitumor efficacy. Twice-daily i.v. administration of this agent is associated with more hepatotoxicity than previously reported in trials using subcutaneous or once daily i.v. administration. Retinal vein thrombosis may be a late complication of i.v. rTNF at this dose and schedule.
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PMID:A phase II trial of recombinant tumor necrosis factor in patients with advanced colorectal carcinoma. 238 95