High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.
OBJECTIVE
The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer.


METHODS
One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease.


RESULTS
Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months).


CONCLUSIONS
This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.
Conte
P F
PF
Gruppo Oncologico Nord-Ovest, Pisa, Italy.
Bruzzone
M
M
Carnino
F
F
Gadducci
A
A
Algeri
R
R
Bellini
A
A
Boccardo
F
F
Brunetti
I
I
Catsafados
E
E
Chiara
S
S
Foglia
G
G
Gallo
L
L
Iskra
L
L
Mammoliti
S
S
Parodi
G
G
Ragni
N
N
Rosso
R
R
Rugiati
S
S
Rubagotti
A
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D015996:Survival Rate; D016896:Treatment Outcome
D015251:Epirubicin; D003520:Cyclophosphamide; D002945:Cisplatin