Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease.
OBJECTIVE
There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting.


METHODS
Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities.


RESULTS
Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program.


CONCLUSIONS
Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.
Markman
M
M
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Hakes
T
T
Reichman
B
B
Lewis
J L
JL
Rubin
S
S
Jones
W
W
Almadrones
L
L
Pizzuto
F
F
Hoskins
W
W
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000188:drug therapy*; D004341:Drug Evaluation; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use*; D015080:Mesna / Q000627:therapeutic use*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010984:Platinum / Q000627:therapeutic use
D010984:Platinum; D015080:Mesna; D007069:Ifosfamide