Summary
Seventeen patients with advanced colorectal carcinoma were treated with a combination of 5-fluorouracil and spirogermanium, a recently developed azaspiran-germanium compound remarkable for its lack of hematologic, gastrointestinal, renal or hepatic toxicity. Response to treatment and the incidence and severity of toxicity were evaluated. No patient achieved a complete response; there were three partial responses. Toxicity was unexpectedly frequent and severe; one patient was removed from study early due to intractable diarrhea, and there were two toxic deaths, both attributable to neutropenia and sepsis. Significant toxicity occurred in all seventeen patients, including three instances of Grade 3 or 4 hematologic toxicity. Given the low response rate and high incidence of life-threatening toxicity, we do not recommend further evaluation of this schedule of 5-fluorouracil and spirogermanium in the treatment of colorectal carcinoma.
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References
Moertel CG: Clinical management of advanced gastrointestinal cancer. Cancer 36:675–682, 1975
Schein PS, Kisner D, MacDonald JS: Chemotherapy of large intestinal carcinoma. Cancer 36:2418–2420, 1975
Carter SK: Large bowel cancer: The current status of treatment. J Natl Cace Inst 56:3–10, 1976
Machover D, Schwartzenberg L, Goldschmidt E, Tourani JM, Michalski B, Hayat M, Dorval T, Misset JL, Delouche C, Brochen D, Fraioli JP, Jasmin C, Maral R, Mathe G: Treatment of advanced colorectal and gastric adenocarcinomas with 5-FU combined with high-dose folinic acid: A pilot study. Cancer Treat Rep 66:1803–1807, 1982
Moertel CG: Chemotherapy of gastrointestinal cancer. N Engl J Med 299:1049–1052, 1978
Falkson G, Falkson HC: Fluorouracil, methyl-CCNU and vincristine in cancer of the colon. Cancer 38:1468–1470, 1976
Rice L, Wheeler JW, Geschickten CF: Synthesis of 4, 4-dialkyl-4-germacyclohexanone and 8, 8-dialkyl-8-germaspiro (4,5) decanes. J Heterocyclic Chem 11:1041–1047, 1974
Schein PS, Slavik M, Smythe T, Hoth D, Smith F, Macdonald JS, Wooley PV: Phase I clinical trial of spirogermanium. Cancer Treat Rep 64:1051–1056, 1980
Mattsson W: A Phase I study of spirogermanium (abstr). Proc Amer Assoc Cancer Res 21:194, 1980
Trope C, Mattsson W, Gynning I, Johnsson JE, Sigurdsson K, Orbert B: Phase II study of spirogermanium in advanced ovarian malignancy. Cancer Treat Rep 65:119–120, 1981
Legha SS, Ajani JA, Bodey GP: Phase I study of spirogermanium given daily. J Clin Oncol 1:331–336, 1983
Rahman A, Green DC, Klein I, Schein PS: Murine antitumor studies with spirogermanium in combination with other anticancer agents (abstr). Proc Am Assoc Cancer Res 25:319, 1984
Hill BT, Bellamy AS, Metcalfe S, Hepburn PJ, Masters JRW, Whelan RDH: Identification of synergistic combinations of spirogermanium with 5-fluorouracil or cisplatin using a range of human tumor cell lines in vitro. Invest New Drugs 2:29–33, 1984
Curreri AR, Ansfield FJ, McIver FA, Waisman HA, Heidelberger C: Clinical studies with 5-fluorouracil. Cancer Res 18:478–484, 1958
Jacobs EM, Luce JK, Wood DA: Treatment of cancer with weekly intravenous 5-fluorouracil. Cancer 22:1233–1238, 1968
Horton J, Olson KB, Sullivan J, Reilly C, Shnider B, the Eastern Cooperative Oncology Group: 5-fluorouracil in cancer: An improved regimen. Ann Intern Med 73:897–900, 1970
Ansfield F, Klotz J, Nealon T, Ramirez G, Minton J, Hill G, Wilson W, Davis H, Cornell G: A Phase III study comparing the clinical utility of four regimens of 5-fluorouracil. Cancer 39:34–40, 1977
Brenner DE, Rosenshein NB, Dillon M, Jones HW, Forastiere A, Tipping S, Burnett LS, Greco FA, Wiernik PH: Phase II study of spirogermanium in patients with advanced carcinoma of the cervix. Cancer Treat Rep 69:457–458, 1985
Brenner DE, Jones HW, Rosenshein NB, Forastiere A, Dillon M, Grumbine F, Tipping S, Burnett S, Greco FA, Wiernik PH: Phase II evaluation of spirogermanium in advanced ovarian carcinoma. Cancer Treat Rep 67:193–194, 1984
Weiss HD, Walker MD, Wiernik PH: Neurotoxicity of commonly used antineoplastic agents (Part I). N Engl J Med 291:75–81, 1974
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McMaster, M.L., Anthony Greco, F., Johnson, D.H. et al. An evaluation of combination 5-fluorouracil and spirogermanium in the treatment of advanced colorectal carcinoma. Invest New Drugs 8, 87–92 (1990). https://doi.org/10.1007/BF00216930
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DOI: https://doi.org/10.1007/BF00216930