Summary
Pancreatic cancer is the fifth leading cause in cancer related death among adults in the United States. Thirtythousand new cases of pancreatic cancer are diagnosed each year, most are metastatic at diagnosis and no effective systemic therapy is available. 773U82 mesylate is one of a series of compounds (arylmethylaminopropanediols-AMAPS) which was synthesized at the Wellcome Research Laboratories. AMAPS bind to DNA, show evidence of topoisomerase 2 inhibition and are active in a variety of murine and human preclinical screens. Based on these data a phase II trial of 773U82 mesylate administered at 800 mg/ m2 daily × 3 at a 4 h infusion repeated every three weeks was carried out. Patients eligible for these trials had histologic proof of adenocarcinoma, good performance status, and normal organ function. This was a multi-institutional trial. Nineteen patients were entered; 15 patients were fully eligible and 4 were ineligible, but were evaluated. Thirteen patients were fully evaluable for response and no response was seen. Median time to progressive disease among eligible patients was 56 days. Toxicity of 773U82 mesylate was myelosuppression which was not prohibitive. 773U82 mesylate is not active in pancreatic cancer.
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References
Boring CC, Squires TS, Tong T: Cancer Statistics, 1991 CA: A Journal of Clinicians 41:19–51, 1991
Brennen MF, Kinsella T, Friedman M: Cancer of the pancreas. In: Cancer: Principles and Practice of Oncology, 3rd edition, DeVita VT, Hellman S, Rosenberg SA (eds) 1989, pp 800–835
Forrest JR, Longmire WP Jr: Carcinoma of the pancreas and periampullary region: a study of 279 patients. Ann Surg 189:129–134, 1979
Brooks JR: Operative approach to pancreatic cancer. Semin Oncol 6:357–365, 1979
Monge JJ, Judd ES, Gage RP: Radical pancreaticoduodenectomy: a 22 year experience with the complications, mortality rate and survival rate. Ann Surg 160: 711–716, 1964
Tepper J, Nardi G, Sut H: Carcinoma of the pancreas. Review of the MGH experience: indications for radiation therapy. Cancer 37:1519–1524, 1976
Wiggans G, Wooley PV, MacDonald J, Smythe T, Ueno W, Schein PS: Phase II trial of streptozotocin, mitomycin and 5-fluorouracil (SMF) in the treatment of advanced pancreatic cancer. Cancer 41:387–391, 1978
Waddell WR: Chemotherapy for carcinoma of the pancreas. Surgery 74:420, 1973
Kovach JS, Moertel CG, Schutt AJ, Hahn RG, Reitemeier RJ: A controlled trial of combined 1,3 Bis(2-chloroethyl)-1-Nitrosourea and 5-fluorouracil therapy for advanced gastric and pancreatic cancer. Cancer 33:563–567, 1974
Cullinan S, Moertel CG, Wieand HS, Schutt AJ, Krook JE, Foley JF, Norris BD, Kardinal CG, Tschetter LK, Barlow JF: A phase III trial of the therapy of advanced pancreatic carcinoma. Evaluations of the mallinson regimen and combined 5-fluorouracil, doxorubicin, and cisplatin. Cancer 65:2207–2212, 1990
Moertel CG, Childs DS, Reitmeier RJ, Colby MY, Jr, Holbrook MA: Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 2:865–869, 1969
Bair K, Andrews C, Tuttle R, Knick VC, Cory M, McKee DD: Synthesis and antitumor activity of a novel series of DNA intercalators. Northeast Regional Meeting 15, Nerm 15, Hosted by the Mid-Huston Section of the American Chemical Society, 1985
Bair KW, Andrews CW, Tuttle RL, Knick VC, McKee DD, Cory M: Biophysical studies and murine antitumor activity of arylmethylaminopropanediols (AMAPS), a new class of DNA binding drugs. Proc Am Assoc Cancer Res 27:424, 1986
Carter CA, Bair KW: Effects of arylmethylaminopropanediols (AMAPS) and established agents on macromolecular synthesis in MCF-7 cells. Proc Am Assoc Cancer Res 31:396, 1990
Bellamy W, Dorr R, Bair KW: Cytotoxicity and mechanisms of action of 3 arylmethylaminopropanediols (AMAPS). Proc Am Assoc Cancer Res 30:562, 1989
Carbone PP, Lucas SV, Alberti DB, Arzoomanian RZ, Tombes MB, Trump DL, Remick SR, Wargin WA, Tuttle RL, Frontiera M, Kohler P, Sparks C, Nieting L, Bailey H, Wilding G: Phase I evaluation of BWA773UHCL(BWA773) in two hour infusion repeated daily × 3. Proc Am Assoc Cancer Res 30:247, 1989
Havlin K, Kuhn J, Craig J: Phase I clinical and pharmacokinetic study of BWA773U, an arylmethylaminopropanediol. Proc Am Soc Clinic Oncol 79:306, 1989
Gehan EA: The determination of the number of patients required in a preliminary and follow-up trial of a new chemotherapeutic agent. J Chron Dis 13:346–353, 1961
Blyth CR, Still HA: Binomial confidence intervals. J Am Stat Assoc 78:108–116, 1983
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Trump, D.L., Hathorn, J.A., Grochow, L.B. et al. Phase II evaluation of the AMAP, 773U82 mesylate, in pancreatic cancer. Invest New Drugs 12, 273–276 (1994). https://doi.org/10.1007/BF00873040
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DOI: https://doi.org/10.1007/BF00873040