Phase II study of intravenous adenosine 5'-triphosphate in patients with previously untreated stage IIIB and Stage IV non-small cell lung cancer
Tóm tắt
Fifteen patients with Stage IIIB or IV non-small cell lung cancer gave informed consent to receive three or more 96-hour infusions of ATP at a dose of 50 mcg/kg/min or higher to determine whether ATP has antineoplastic activity against this tumor type and to better define the spectrum of toxicity for ATP given as a single agent. There were no objective complete or partial responses observed. The median survival of the overall group was 187 days and the median time to tumor progression was 113 days. The major toxic side effects were chest pain and dyspnea, leading to the cessation of treatment in 5 patients. We conclude that ATP at this dose and schedule of administration is an inactive agent in patients with advanced non-small cell lung cancer.
Tài liệu tham khảo
Trams EG, Kaufman H, Burnstock GA: Proposal for the role of ecto-enzymes and adenylates in traumatic shock. J Theor Biol 87:609-621, 1980
Rapaport E: Treatment of human tumor cells with ADP and ATP yields arrest of growth in the S phase of the cell cycle. J Cell Physiol 114:279-283, 1983
Beyer EC, Steinberg TH: Evidence that the gap junction protein connexin-43 is the ATP-induced pore of mouse macrophages. J Biochem 266:7971-7974, 1991
Lowenstein WR: The cell to cell channel of gap junctions. Cell 48:725-726, 1987
Vandewalle B, Hornez L, Revillion F, Lefebvre J: Effect of extracellular ATP on breast tumor cell growth, implication of intracellular calcium. Cancer Lett 8547-54, 1994
Zheng LM, Zychlinsky A, Liu C-C, Ojcius DM, Ding E, Young J: Extracellular ATP as a trigger for apoptosis or programmed cell death. J Cell Biol 112:279-288, 1991
Pranzi E, Djeu JY, Hoffman SL, Epling-Burnette PK, Blanchard DK: Lysis of leukemia cells by extracellular adenosine triphosphate: Mechanism and characterization of the adenosine triphosphate receptor. Blood 82:1578-1585, 1993
Rapaport E, Fontaine J: Anticancer activities of adenine nucleotides in mice are mediated through expansion of erythrocyte ATP pools. Proc Natl Acad Sci USA 86:1662-1666, 1989
Lasso de la Vega MC, Terradez P, Obrador E, Navarro J, Pellicer JA, Estrela JM: Inhibition of cancer growth and selective glutathione depletion in Ehrlich tumour cells in vivoby extracellular ATP. Biochem J 298:99-105, 1994
Abraham EH, Prat AG, Gerweck L, Seneveratne T, Arceci RJ, Kramer R, Guidotti G, Cantiello HF: The multidrug resistance (mdr1) gene product functions as an ATP channel. Proc Natl Acad Sci USA 90:312-316, 1993
Maymon R, Maymon BBS, Cohenarmon M, Holtzinger ML, Leibovici J: Enhancing effect of ATP on intracellular Adriamycin penetration in human ovarian cancer cell lines. Biochem Biophys Acta 1201:173-178, 1994
Haskell CM, Wong M, Williams A, Lee L-Y: Phase I trial of extracellular adenosine 50-triphosphate in patients with advanced cancer. Med Pediatr Oncol 27:165-173, 1996
Aaronson NK, Ahmedzia S, Bergman B: The European Organization for Research and Treatment of Cancer QLC-C30: A Quality of Life Instrument for use in International Clinical Trials in Oncology. J Natl Cancer Inst 85:365-376, 1993
Bergman B, Aaronson NK, Ahmedzia S: The EORTC QLQLC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. Eur J Cancer 30A:635-642, 1994
Simon R: Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1-10, 1989
Figlin RA, Holmes EC, Turrisi AT: Non-small cell lung cancer. In: Haskell CM (ed) Cancer Treatment, 4th edition. W.B. Saunders Company, Philadelphia 1995, pp 385-413.