Enhanced antitumor activity of an adriamycin + 5-fluorouracil combination when preceded by biochemical modulation.
A three-drug combination, PMA, consisting of (phosphonacetyl)-L-aspartic acid + 6-methylmercaptopurine riboside + 5-aminonicotinamide, preceding either 5-fluorouracil (5-FU) or adriamycin (Adr), produced tumor-regressing activity in a murine advanced breast tumor model not attainable with either 5-FU or Adr as single agents, or with any lesser combination of these drugs administered at maximally tolerated doses. Marked tumor-regressing activity was further increased significantly by using 5-FU and Adr together in conjunction with the modulatory biochemical conditioning (particularly ATP depletion) provided by pretreatment with PMA.
Stolfi
R L
RL
Catholic Medical Center, Woodhaven, NY 11421, USA.
Colofiore
J R
JR
Nord
L D
LD
Martin
D S
DS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy; D015122:Mercaptopurine / Q000008:administration & dosage / Q000031:analogs & derivatives; D051379:Mice; D009536:Niacinamide / Q000008:administration & dosage; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D009536:Niacinamide; D001224:Aspartic Acid; C010240:6-methylthiopurine; C013195:sparfosic acid; D004317:Doxorubicin; D015122:Mercaptopurine; D010746:Phosphonoacetic Acid; D005472:Fluorouracil