Family history of cancer rather than p53 status predicts efficacy of pegylated liposomal doxorubicin and oxaliplatin in relapsed ovarian cancer.
BACKGROUND
The aim of the study was to assess the efficacy of pegylated liposomal doxorubicin (PLD) and oxaliplatin in patients affected by relapsed epithelial ovarian cancer with a family history of BRCA and p53 mutations.


METHODS
Seventy-two women received a median of 7.5 courses of PLD at 30 to 35 mg/m2 plus oxaliplatin at 70 mg/m2, and associations between BRCA1/2 and TP53 status and overall survival (OS) were determined. Thirty-eight had a short platinum-free interval (PFI; <12 months), and 34 had a long PFI (> or =12 months).


RESULTS
Nine patients had BRCA1 mutations, and 1 had a BRCA2 mutation. Platinum sensitivity was associated with OS (P = 0.0001). At a median follow-up of 9.3 months, objective response rate, median time to progression, and OS were 47.3%, 5.8 months, and 12.9 months, respectively, in short PFI compared with the 76.5%, 11.5 months, and 47.7 months in long PFI. p53 status did not correlate to these parameters. The median time to progression was 11.5 months for high-risk patients versus 6.5 months for patients with sporadic cancer (P = 0.0188), and the median OS from the start of treatment was 48.7 and 16.2 months (P = 0.0032), respectively. Toxicity was mostly grade 1 or 2.


CONCLUSIONS
High response rates in the long-PFI patients indicate that this treatment is beneficial and well tolerated. Platinum sensitivity and positive family history and/or a BRCA1/BRCA2 mutation are a useful predictor of response.
Nicoletto
Maria Ornella
MO
Istituto Oncologico Veneto-IRCCS, Department of Pathology, University of Padova, via Gattamelata 64, Padova, Italy. mariaorn@libero.it
Bertorelle
Roberta
R
Borgato
Lucia
L
De Salvo
Gian Luca
GL
Artioli
Grazia
G
Lombardi
Giuseppe
G
Zustovich
Fable
F
Marcato
Raffaella
R
Parenti
Anna
A
Montagna
Marco
M
Donach
Martin E
ME
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology; D024522:Genes, BRCA2 / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000077150:Oxaliplatin; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; C506643:liposomal doxorubicin; D000077150:Oxaliplatin; D011092:Polyethylene Glycols; D004317:Doxorubicin