p53 Gene status and response to topotecan-containing chemotherapy in advanced ovarian carcinoma.
OBJECTIVE
Since the p53 gene has been identified as a determinant of response to chemotherapy in ovarian carcinoma in previous studies, we investigated the significance of the p53 status in response to topotecan as second-line therapy.


METHODS
Twenty-eight patients with advanced ovarian carcinoma, pretreated with standard platinum/paclitaxel chemotherapy, received topotecan as single-agent second-line therapy. Tumors were investigated by molecular analysis for p53 mutations in tumor samples obtained at primary surgery (i.e. before first-line therapy).


RESULTS
Wild-type p53 tumors responsive to first-line therapy maintained substantial responsiveness to topotecan. In contrast, p53 mutation was associated with a low responsiveness to second-line therapy.


CONCLUSIONS
The better outcome in relapsed patients with wild-type p53 suggests that the presence of a functional wild-type p53 confers stability of the drug-sensitive phenotype. This outcome is consistent with the clinical observation that the efficacy of topotecan in the treatment of relapsed ovarian carcinoma patients is dependent on platinum sensitivity, because platinum-sensitive tumors are expected to carry wild-type p53. Although untreated mutant p53 tumors may be responsive to first-line paclitaxel-containing therapy, it is likely that loss of p53 leads to genomic instability resulting in rapid progression to drug resistance.
Oggionni
M
M
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italia.
Pilotti
S
S
Suardi
S
S
Ditto
A
A
Luoni
C
C
Mariani
L
L
Scambia
G
G
Fanfani
F
F
Zunino
F
F
D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D016158:Genes, p53; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D019772:Topotecan / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019772:Topotecan