In a phase II trial of
ifosfamide 2 g/m2 days 1 to 4 with
mesna uroprotection in 124 patients who had previously failed treatment for
sarcomas, 3% achieved a complete response (CR), and 18% had a CR or partial response (PR). In the subset of patients with
soft-tissue sarcomas, the response rate for the 64 patients who received bolus administration was 26% compared with 9% for the 60 patients who received a continuous infusion (Cl) schedule (P = .03). When
mesna was unavailable, the incidence of
hematuria was significant in patients, with three of four patients affected. Microscopic
hematuria was uncommon in patients receiving
mesna.
Hematuria in the group as a whole was not associated with prior treatment with
cyclophosphamide, pelvic
radiotherapy, age, or a bolus versus Cl schedule. Thus, this and other studies confirm that
ifosfamide is active in failed
sarcomas. In sequential phase I/II trials, 111 patients who were previously untreated for metastatic or inoperable
sarcomas received
doxorubicin,
ifosfamide,
dacarbazine at doses of 60, 7,500, and 900 mg/m2, respectively, by Cl over 72 hours; myelosuppression was dose-limiting. Eleven patients (10%) achieved CRs, with an overall response rate of 47%. Most responses (approximately 70%) were observed within two cycles, and median times to progression were 10 and 9 months for CR and PR, respectively. Following CR, two patients remained disease-free at 32 and 16 months. Of 15 additional patients rendered disease-free with surgery following at least a minor response to
chemotherapy, two remained disease-free at 30 and 18 months with no further
therapy. Central nervous system (CNS)
metastases developed in 11 patients, all of whom had high-grade
sarcomas; seven of these patients were still responding systemically (three CRs). This regimen is undergoing evaluation in a randomized trial versus
doxorubicin and
dacarbazine alone in untreated advanced
sarcoma and is being compared with observation in the adjuvant treatment of high-grade
sarcomas.(ABSTRACT TRUNCATED AT 400 WORDS)