Evaluation of ifosfamide plus mesna as first-line chemotherapy in women with metastatic breast cancer.
Ifosfamide is an oxazaphosphorine analogue of cyclophosphamide with proven activity in breast cancer but substantial urotoxicity. The introduction of mesna as a uroprotective agent provided a stimulus for reexamination of ifosfamide for therapy of women with metastatic breast cancer. Twenty women with measurable (18 patients) or evaluable (2 patients) disease were entered into a phase II clinical trial of ifosfamide plus mesna as first-line chemotherapy. Ifosfamide was administered i.v. at a dose of 1,800 mg/m2 in 1 L D5W over 2 h on five consecutive days. Mesna was administered i.v. at a dose of 400 mg/m2 over 15 min immediately before and 1 h after ifosfamide, and then every 4 h for three more doses. The last three doses could be given either i.v. or orally. The planned cycle length was 28 days. Three patients (15%), all with measurable disease, achieved a partial response (95% confidence interval: 3 to 38%). Median time to progression was 137 days and median survival was 407 days. Toxicities included cumulative myelosuppression and substantial nausea and emesis. Four patients were removed from treatment because of toxicity alone and a fifth refused further therapy. We conclude that ifosfamide, plus mesna, as given in this protocol has definite but limited antitumor activity and poor tolerability.
Ingle
J N
JN
Mayo Clinic, Rochester, Minnesota 55905, USA.
Krook
J E
JE
Mailliard
J A
JA
Hartmann
L C
LC
Wieand
H S
HS
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003556:Cystitis / Q000139:chemically induced / Q000517:prevention & control; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015080:Mesna / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012074:Remission Induction
D018906:Antineoplastic Agents, Alkylating; D015080:Mesna; D007069:Ifosfamide