Antitumor activity of the combination of synthetic retinoid ST1926 and cisplatin in ovarian carcinoma models.
BACKGROUND
The novel adamantyl retinoid ST1926 is a potent inducer of apoptosis in ovarian carcinoma cells. Since the pro-apoptotic effect is associated with activation of p53, in this study we have investigated the efficacy of combination of ST1926 with cisplatin, a DNA-damaging agent that is known to induce p53-dependent apoptosis.


METHODS
The efficacy of ST1926 and its combination with cisplatin was evaluated in human ovarian carcinoma models, including resistant tumors.


RESULTS
Oral treatment with ST1926 alone caused a marginal tumor growth inhibition (<50%), but the combination with cisplatin resulted in an improved efficacy, most evident in terms of tumor growth delay without a substantial increase of toxicity. The combination therapy achieved the best effects against the HOC18 ovarian carcinoma tumor, resulting in an appreciable number of animals without evidence of disease at the end of the experiment. In contrast to the marginal effect of ST1926 alone against the subcutaneous-growing tumors, loco-regional (intraperitoneal) treatment achieved a marked increase of survival of animals with ascitic IGROV-1 tumor.


CONCLUSIONS
The present results document the efficacy of the combination of cisplatin with ST1926 and provide a rational basis for the design of novel, well-tolerated platinum-based treatment approaches in human ovarian carcinoma.
Pisano
C
C
Research and Development, Sigma-Tau, Pomezia (Rome), Italy.
Vesci
L
L
Foderà
R
R
Ferrara
F F
FF
Rossi
C
C
De Cesare
M
M
Zuco
V
V
Pratesi
G
G
Supino
R
R
Zunino
F
F
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002934:Cinnamates / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C472791:3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid; D002934:Cinnamates; D000218:Adamantane; D002945:Cisplatin