Phase II trial of piroxantrone for advanced or metastatic soft tissue sarcomas
Investigational New Drugs - 1993
Tóm tắt
Piroxantrone is an anthrapyrazole compound undergoing phase II testing in a variety of diseases. The anthrapyrazoles are a series of compounds synthesized with the intent of maintaining the broad antitumor activity of anthracyclines, but with lessened cardiac toxicity. The Southwest Oncology Group (SWOG) conducted a phase II trial of piroxantrone in advanced soft tissue sarcoma. Treatment consisted of piroxantrone 150 mg/M2 administered intravenously over 1 hour every 21 days. Twenty-five eligible patients were registered to the trial. Twenty-three patients received treatment and are fully evaluable for response and toxicity. Two partial responses were seen for an overall response rate of 9% (95% confidence limit 1%–28%). Abnormal cardiac ejection fraction occurred in five patients, and fatal congestive heart failure developed in one patient on study. Toxicities other than cardiac were tolerable. Based on the observed response rate and cardiac toxicity, further trials of piroxantrone in the treatment of soft tissue sarcoma do not appear warranted.
Từ khóa
Tài liệu tham khảo
Chang AE, Rosenberg SA, Glatstein EJ, Antman KH: Sarcomas of soft tissues. In: Cancer Principals and Practice of Oncology. 3rd Edition. J.B. Lippincott, Philadelphia PA, 1989, pp 1345–1398
Von Hoff DD, Layard MW, Basa P, Davis Jr. HL, Von Hoff AL, Rozencweig M, Young RC, Muggia FM: Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717, 1979
Doroshow JH: Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res 43:460–472, 1983
Showalter HDH, Johnson JL, Werbel LM, Leopold WR, Jackson RC, Elslager EF: 5-[(Aminoalkyl)amino]-substituted anthral [1,9-crf]pyrazol-6(2H)-ones as novel anticancer agents. Synthesis and biological evaluation. J Med Chem 27:253–255, 1984
Hacker MP, Newman RA, Fagan MS: The fetal mouse heart: a potential model for anthracycline-induced cardiotoxicity. Drugs Exp Clin Res 9:39–44, 1983
Fry DW, Boritzki TJ, Besserer JA, Jackson RC:In vitro DNA strand scission and inhibition of nucleic acid synthesis in L1210 leukemia cells by a new class of DNA complexers, the anthra[1,9-crf]pryazol-6(2H)-ones (anthrapyrazoles). Biochem Pharmacol 34:3499–3508, 1985
Hantel A, Donehower RC, Rowinsky EK, Vance E, Clarke BV, McGuire WP, Ettinger DS, Noe DA, Grochow LB: Phase I study and pharmacodynamics of piroxantrone (NSC 349174), a new anthrapyrazole. Cancer Res 50:3284–3288, 1990
Ames MM, Loprinzi CL, Collins JM, van Haelst-Pisani C, Richardson RL, Rubin J, Moertel CG: Phase I and clinical pharmacological evaluation of piroxantrone hydrochloride (Oxantrazole). Cancer Res 50:3905–3909, 1990
Miller A, Hoogstraten B, Staquet M, Winkler A: Reporting results of cancer treatment. Cancer 47:207–214, 1981
Clarke BV, Harwood KV, Donehower R: Local toxicity of piroxantrone: an anthrapyrazole with irritant and vesicant properties similar to doxorubicin (letter). J Natl Cancer Instit. 81:1331–1332, 1989
Allen A, Wolf M, Crawford ED, Davis MP, Natale RB, Barnett ML: Phase II evaluation of piroxantrone in renal cell carcinoma: A Southwest Oncology Group Study. Inv N Drugs 10:129–132, 1992
Williamson SK, Crowley JJ, Livingston R, Hantel A, Doroshow JH: Phase II trial of piroxantrone in advanced non-small cell carcinoma of the lung: A Southwest Oncology Group Study. Inv N Drugs 10:29–30, 1992
Savarese D, Berg S, Denicoff A, Hillig M, O'Shaughnessy J, Otterson G, Balis F, Poplack D, Cowan K. Phase I/pharmacokinetic study of piroxantrone and granulocyte colonystimulating factor (G-CSF) (Meeting abstract) Proc. AACR 33:1459, 1992
Zalupski M, Metch B, Balcerzak S, Fletcher WS, Chapman R, Bonnet JD, Weiss GR, Ryan J, Benjamin RS, Baker LH: Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: A Southwest Oncology Group Study. J Natl Cancer Inst. 83:926–932, 1991