ABSTRACT
BACKGROUND: We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. METHODS: Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. RESULTS: Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens. CONCLUSION: Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.
Subject(s)
Peptides, Cyclic/administration & dosage , Uterine Cervical Neoplasms/drug therapy , Adult , Area Under Curve , Double-Blind Method , Down-Regulation/drug effects , Female , Half-Life , Humans , Injections, Intralesional/methods , Middle Aged , Nuclear Proteins/metabolism , Nucleophosmin , Uterine Cervical Neoplasms/metabolismABSTRACT
The charts of 17 patients (12 male), aged 7 to 65 years old, with chronic pancreatitis that were operated in three different Chilean regions, were reviewed. Results: Seven patients had previous endoscopic therapeutic procedures (papillotomy in 4 and stent placint in 3). Seven patients had been subjected to previous biliary surgical procedures. Indications for surgery were severe pain in 14 patients, the suspicion of a pancreatic carcinoma in 4 patients, an infected pseudocyst in one and massive bleeding of multiple pseudo-aneurysms in a pseudocysts in one patient. Twelve patients were subjected to decompressions and 5 to pancreatic resections. There was no operative mortality and one transient pancreatic fistula. After an average follow up of 22 months, pain improved in 94 percent of cases, pancreatic cancer was diagnosed in one patient and 79 percent of subjects gained weight. One patient became insulin dependent, one increased his insulin requirements and one bad transient steatorrhea, since she could not afford pancreatic enzyme replacement therapy. Conclusions: The multidisciplinary approach of patients with chornic pancreatitis, with selective use of surgery, may greatly improve their quelity of life