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A phase II study of Temozolomide in advanced untreated pancreatic cancer

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Abstract

Temozolomide (SCH 52365) is an imidazotetrazine derivative which exhibits broad spectrum activity against murine tumors and is structurally related to dacarbazine (DTIC). Temozolomide cytotoxicity is schedule dependent in vivo with a daily × 5 schedule showing the highest activity. Oral temozolomide is rapidly and completely absorbed with minimal interpatient and intrapatient variability in pharmacokinetics. Clinical studies have demonstrated activity against melanoma and glioma. The present study examined the activity of oral temozolomide against patients with pancreatic cancer. Patients with advanced pancreatic adenocarcinoma previously untreated with chemotherapy received temozolomide 200 mg/m2/day once daily orally for 5 days with cycles repeated every 28 days. There were 16 patients entered on study with 15 evaluable for response and toxicity. There were no responses seen in 15 evaluable patients with 14 manifesting progressive disease within 2 months of starting therapy. Toxicity was primarily hematological with 3 patients experiencing ≥ grade 3 neutropenia and thrombocytopenia respectively. Other toxicities were relatively modest. In conclusion, temozolomide in the once daily × 5 schedule is inactive against adenocarcinoma of the pancreas.

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References

  1. Stevens MFG, Hickman JA, Stone R, Langdon SP. Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methylimidazotetrazoneone, a novel drug with potential as an alternative to dacarbazine. Cancer Research 47: 5846-5852, 1987.

    Google Scholar 

  2. Tsang LLH Quarterman CP, Gescher A, Slack JA. comparison of cytotoxicity in vitroof temozolomide and dacarbazine, prodrugs of MTIC. Cancer Chemother Pharmacol 27: 342-346, 1991.

    Google Scholar 

  3. Du DL, Volpe DA, Grieshaber CK, Murphy MJ. In vitromyelotoxicity of 2-3'-dideoxynucleosides on human hematopoietic progenitor cells. Exp Hematol 18: 832-836, 1991.

    Google Scholar 

  4. Newlands ES, Blackledge GR, Slack JA, Ruiestin GJ. Phase I trial of temozolomide. Br J Cancer 65: 287-291, 1992.

    Google Scholar 

  5. O'Reilly SM, Newlands ES, Glaser MG. Temozolomide, a new oral cytotoxic chemotherapy agent with promising activity against brain tumors. Eur J Cancer 29A: 940-945, 1993

    Google Scholar 

  6. Bleehan NM, Newlands ES, Lee SM, Thatcher N, Selby P, Calvert AH, Rustin GJS, Brampton M, Stevens MFG. Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma. J Clin Oncol 13: 910-913, 1995.

    Google Scholar 

  7. Liu L, Markowitz S, Gerson SL. Mismatch repair mutations override alkyltransferase in conferring resistance to temozolomide but not to BCNU. Cancer Research 56: 5375-5379, 1996.

    Google Scholar 

  8. Wedge SR, Porteous JK, Newlands ES. 3-aminobenzamide and/or O6-benzylguanine evaluated as an adjuvant to temozolomide or BCNU treatment in cell lines of variable mismatch repair status and O6-alkylguanine-DNA alkyltransferase activity. Br J Cancer 74: 1030-1036, 1996.

    Google Scholar 

  9. Lacal PM, D'Atri S, Orlando L, Bonmassar E, Graziani G. In vitroinactivation of human O6-alkylguanine-DNA alkyltransferase by antitumor triazene compounds. J Pharm Exp Therapeutics 279: 416-422, 1996.

    Google Scholar 

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Moore, M.J., Feld, R., Hedley, D. et al. A phase II study of Temozolomide in advanced untreated pancreatic cancer. Invest New Drugs 16, 77–79 (1998). https://doi.org/10.1023/A:1006043332368

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  • DOI: https://doi.org/10.1023/A:1006043332368

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