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


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.


CONCLUSIONS
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.
Papageorgiou
Athanasios
A
Department of Experimental Chemotherapy, Symeonidion Research Center, Thessaloniki, Greece. gerom@chem.auth.gr
Andreadis
Charalambos
C
Boutis
Anastasios
A
Lialiaris
Theodoros S
TS
Mouratidou
Despina
D
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D001378:Azasteroids / Q000008:administration & dosage / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D001378:Azasteroids; D009588:Nitrogen Mustard Compounds; C017888:NSC 290205; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone