Docetaxel enhances tumor radioresponse in vivo

Kathryn A. Mason, Nancy R. Hunter, Kresimira Milas, James L. Abbruzzese, Luka Milas

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Although the radiosensitizing potential of paclitaxel has been investigated extensively in cancer treatment, a sister taxane, docetaxel, has been studied rarely. We investigated the ability of docetaxel to enhance in vivo tumor radioresponse and influence radiation injury to normal tissue. In addition, mitotic arrest and apoptosis in tumors and normal tissues were assessed after docetaxel administration to determine whether these cellular effects underly its radiomodifying action. Mice bearing in their legs 8-mm isotransplants of a murine mammary carcinoma, designated MCA-4, were treated with 33 mg/kg docetaxel i.v., 9-21 Gy single-dose local tumor irradiation, or both (in which case radiation was given 9 or 48 h after docetaxel). Tumor growth delay was the end point of the treatments. Mitotic arrest and apoptosis were assayed 1-72 h after treatment with docetaxel. Normal tissue radioresponse was determined using jejunal crypt cell survival 3.5 days after mice were exposed to 9.2-14.8 Gy single-dose, total-body irradiation; the mice were treated with 33 mg/kg docetaxel i.v. 3, 9, or 48 h before irradiation. Docetaxel was assessed for its ability to induce mitotic arrest and apoptosis in jejunum 1-72 h after treatment. Docetaxel induced both mitotic arrest and apoptosis in both tumor and jejunum. Mitotic arrest preceded apoptosis and peaked in the tumor at 9-12 h after treatment; it peaked at 3 h in jejunum. Docetaxel enhanced tumor radioresponse by a factor of 1.45 when the drug was given 9 h before radiation and 2.33 when it was given 48 h before. In contrast, it only slightly enhanced radiation-induced damage of the jejunum and only when given 3 or 9 h before irradiation. Thus, docetaxel given within 2 days before irradiation acted as a potent enhancer of tumor radioresponse and increased the therapeutic gain of irradiation.

Original languageEnglish (US)
Pages (from-to)2431-2438
Number of pages8
JournalClinical Cancer Research
Volume3
Issue number12 I
StatePublished - Dec 1997
Externally publishedYes

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docetaxel
Neoplasms
Jejunum
Apoptosis
Radiation
Therapeutics
Isografts
Radiation Injuries

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mason, K. A., Hunter, N. R., Milas, K., Abbruzzese, J. L., & Milas, L. (1997). Docetaxel enhances tumor radioresponse in vivo. Clinical Cancer Research, 3(12 I), 2431-2438.

Docetaxel enhances tumor radioresponse in vivo. / Mason, Kathryn A.; Hunter, Nancy R.; Milas, Kresimira; Abbruzzese, James L.; Milas, Luka.

In: Clinical Cancer Research, Vol. 3, No. 12 I, 12.1997, p. 2431-2438.

Research output: Contribution to journalArticle

Mason, KA, Hunter, NR, Milas, K, Abbruzzese, JL & Milas, L 1997, 'Docetaxel enhances tumor radioresponse in vivo', Clinical Cancer Research, vol. 3, no. 12 I, pp. 2431-2438.
Mason KA, Hunter NR, Milas K, Abbruzzese JL, Milas L. Docetaxel enhances tumor radioresponse in vivo. Clinical Cancer Research. 1997 Dec;3(12 I):2431-2438.
Mason, Kathryn A. ; Hunter, Nancy R. ; Milas, Kresimira ; Abbruzzese, James L. ; Milas, Luka. / Docetaxel enhances tumor radioresponse in vivo. In: Clinical Cancer Research. 1997 ; Vol. 3, No. 12 I. pp. 2431-2438.
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