Differentiated thyroid cancer can be effectively treated with high-dose 131I and the other head and neck cancer can also be effectively treated with extra-radiotherapy, but these treatments often result in a reduction in salivary gland function, causing xerostomia. Collectively, these effects can lead to severe secondary complications, including difficulty in speaking and swallowing, decreasing appetite even affecting nutrition and sleep. Amifostine, an analog of cysteamine, is a phosphorlyated aminothiol prodrug and its active metabolite, WR-1065 etc, can selectively protect normal tissues from the cytotoxic effects of drugs and/or radiation while preserve antitumor effects. Many studies have demonstrated that amifostine protects normal tissues from both acute and late extra-radiation damage without protecting the tumor. It has been approved by FDA to be used for protecting the salivary gland from xerostomia caused by radiotherapy. It has also show protecting effects on intra-radiotherapy, but there are many problems waiting for study.
Amifostine ; adverse effects ; therapeutic use ; Animals ; Clinical Trials as Topic ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Cytoprotection ; Head and Neck Neoplasms ; drug therapy ; radiotherapy ; Humans ; Rabbits ; Radiation Injuries ; prevention & control ; Radiation-Protective Agents ; pharmacology

BACKGROUND/AIMS: The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA). METHODS: A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches. RESULTS: Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies. CONCLUSIONS: Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile.
Antirheumatic Agents/administration & dosage/adverse effects/*therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Humans ; Janus Kinases/antagonists & inhibitors ; Methotrexate/therapeutic use ; Piperidines/administration & dosage/adverse effects/*therapeutic use ; Protein Kinase Inhibitors/administration & dosage/adverse effects/therapeutic use ; Pyrimidines/administration & dosage/adverse effects/*therapeutic use ; Pyrroles/administration & dosage/adverse effects/*therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome

Antineoplastic Agents ; pharmacology ; therapeutic use ; Benzamides ; Clinical Trials, Phase II as Topic ; Drug Resistance, Neoplasm ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Piperazines ; pharmacology ; therapeutic use ; Pyrimidines ; pharmacology ; therapeutic use