Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients.
BACKGROUND
A phase III multicenter randomized trial has been designed in order to address whether amifostine (WR-2721, Ethyol), an organic thiophosphate cytoprotector, can protect ovarian cancer patients from toxicity induced by carboplatin-paclitaxel chemotherapy.


METHODS
Patients were randomly assigned to receive carboplatin [area under the curve (AUC) 5 mg.min/ml] and paclitaxel (175 mg/m(2)) with (arm A) or without (arm B) amifostine (910 mg/m(2)) every 21 days for six cycles.


RESULTS
One-hundred and eighty-seven patients were accrued: 93 patients in arm A and 94 patients in arm B. There was no difference in terms of erythrocytopenia between the two arms; grade 3-4 thrombocytopenia was higher in arm A (3.3% versus 0.6%; P = 0.0010). There was no significant reduction of grade 3-4 leukopenia in arm A (11.8% versus 13.8%). The incidence of grade 3-4 neutropenia was lower in arm A (31.3% versus 37.9%; P = 0.03), as was the incidence of severe mucositis (4.7% versus 15.4% in arm A versus arm B, respectively; P <0.0001). Finally, amifostine appears to be protective against neurotoxicity (grade 3-4 neurotoxicity 3.7% versus 7.2%; P = 0.02). With a median follow-up of 24 months (range 2-41), time to progression was similar between the two groups.


CONCLUSIONS
We showed that amifostine can exert some protection from the cumulative toxicity associated with this regimen. The results need to be confirmed in other randomized trials with this combination.
Lorusso
D
D
Department of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
Ferrandina
G
G
Greggi
S
S
Gadducci
A
A
Pignata
S
S
Tateo
S
S
Biamonte
R
R
Manzione
L
L
Di Vagno
G
G
Ferrau'
F
F
Scambia
G
G
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004906:Erythrocyte Count; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013280:Stomatitis / Q000139:chemically induced / Q000517:prevention & control; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D016190:Carboplatin; D004999:Amifostine; D017239:Paclitaxel