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In vivo efficacy of marimastat and chemoradiation in head and neck cancer xenografts.

AbstractOBJECTIVE:
To assess the effect of combining a synthetic matrix metalloprotease inhibitor and chemoradiation therapy on tumor growth in a murine model of head and neck squamous-cell carcinoma (SCC).
METHODS:
Athymic, nude mice bearing SCC-1 xenografts were used to comprise 4 treatment groups: (1) control receiving vehicle alone, (2) marimastat alone, (3) cisplatin + radiation in combination and (4) marimastat + cisplatin + radiation in combination. The marimastat was administered at a dose of 8.7 mg/kg/day over a 14-day period via a subcutaneous osmotic pump. The control group received vehicle only via a subcutaneous osmotic pump. Radiotherapy was given in 4 fractions of 8 Gy divided over days 8, 12, 16 and 20 with 4 intraperitoneal doses of cisplatin (3 mg/kg) 1 h before each fraction of radiation.
RESULTS:
Animals receiving triple treatment had delayed growth, measured as lengthened tumor doubling time, compared to the cisplatin + radiation combination (p = 0.03). Also, compared to control, the triple-treatment group (p = 0.005) had delayed growth in terms of doubling time. Factor VIII immunohistochemistry to assess microvessel density did not demonstrate a reduction in neovascularization between the triple-treatment and cisplatin + radiation combination groups. Statistical analysis failed to demonstrate any significant difference among groups.
CONCLUSIONS:
Chemoradiation + marimastat therapy had delayed tumor growth, compared to the chemoradiation alone. Based on these results, marimastat may work in combination with chemotherapy and radiation to inhibit tumor growth.
AuthorsJoni B Skipper, Lacey R McNally, Eben L Rosenthal, Wenquan Wang, Donald J Buchsbaum
JournalORL; journal for oto-rhino-laryngology and its related specialties (ORL J Otorhinolaryngol Relat Spec) Vol. 71 Issue 1 Pg. 1-5 ( 2009) ISSN: 1423-0275 [Electronic] Switzerland
PMID18931526 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright 2008 S. Karger AG, Basel.
Chemical References
  • Antineoplastic Agents
  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • marimastat
  • Cisplatin
Topics
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Carcinoma, Squamous Cell (blood supply, drug therapy, pathology, radiotherapy)
  • Cisplatin (therapeutic use)
  • Female
  • Head and Neck Neoplasms (blood supply, drug therapy, pathology, radiotherapy)
  • Hydroxamic Acids (therapeutic use)
  • Matrix Metalloproteinase Inhibitors
  • Mice
  • Mice, Nude
  • Microcirculation (drug effects, radiation effects)
  • Neoplasm Transplantation
  • Neovascularization, Pathologic (pathology)
  • Protease Inhibitors (therapeutic use)
  • Transplantation, Heterologous
  • Treatment Outcome

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