Synergistic antitumor activity of oxaliplatin in combination with gemcitabine in pancreatic tumor-bearing mice.
Oxaliplatin (OX) and gemcitabine (GEM) are both drugs with proven clinical activity in various tumor types, have no overlapping toxic side effects and are different with respect to cellular metabolism. Therefore, we performed an in vivo study to determine the efficacy of the combination of these two drugs to optimize the scheduling of both substances using pancreatic ductal adenocarcinoma PAN-02, subcutaneously growing in C57Bl mice. A total of 164 mice were used for cytotoxicity and antitumor studies. The combination therapy resulted in better results than those observed when the drugs were administered individually. GEM (58 mg/kg) and OX (1.0 mg/kg) achieved a 52% reduction in tumor size on day 28 after transplantation and a T/C value of 168% when the intermittent treatment schedule on days 1, 4 and 7 after inoculation was used. This treatment schedule was superior to other therapeutic schedules, producing a synergistic antitumor effect much higher than the one expected by the simple addition of the effects by OX and GEM acting independently.
Moschidis
A
A
2nd Hospital IKA, Thessaloniki, Greece.
Papageorgiou
A
A
Atmatzidis
K
K
Tsalis
K
K
Moschidis
E
E
Livanis
J
J
Chrysogelou
E
E
Mourelatos
D
D
Tsavdaridis
D
D
Harlaftis
N
N
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004357:Drug Synergism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine