NSC 290205-based therapy in murine pancreatic adenocarcinoma PAN02 in combination with adriamycin (ADR)

Anticancer Res. 2006 Jan-Feb;26(1A):243-7.

Abstract

Background: NSC 290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. In this study, the antitumor activity of A in combination with ADR (AHOP) was investigated in comparison with the standard CHOP regimen.

Materials and methods: PAN02 adenocarcinoma was used in this study. C57Bl mice were used for chemotherapy evaluation. The activity was assessed from the inhibition of tumor growth and the oncostatic parameter T/C%.

Results: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both the CHOP and AHOP regimens showed significant and comparable antitumor effects. AHOP caused the maximum effect, inhibiting tumor growth by 56.8%. CHOP was less effective, producing 47.7% tumor inhibition.

Conclusion: It is very likely that the D-lactamic steroid (androstan) alkylator forA, containing the amide group -NH-CO-, combined with ADR which intercalates between DNA base-pairs, is the explanation for the higher activity of AHOP as compared to CHOP.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Azasteroids / administration & dosage
  • Azasteroids / pharmacology*
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Cell Line, Tumor
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacology
  • Doxorubicin / administration & dosage
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitrogen Mustard Compounds / administration & dosage
  • Nitrogen Mustard Compounds / pharmacology*
  • Pancreatic Neoplasms / drug therapy*
  • Prednisone / administration & dosage
  • Vincristine / administration & dosage

Substances

  • Azasteroids
  • Nitrogen Mustard Compounds
  • NSC 290205
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol