title: Dana-Farber Cancer Institute studies in advanced sarcoma.
abstract: 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)
authors.affiliation: Division of Clinical Oncology, Dana Farber Cancer Institute, Boston, MA 02115.
authors.forename: K H
authors.initials: KH
authors.lastname: Antman
authors.forename: A
authors.initials: A
authors.lastname: Elias
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002493:Central Nervous System Diseases / Q000139:chemically induced; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008171:Lung Diseases / Q000139:chemically induced; D008297:Male; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012509:Sarcoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D016019:Survival Analysis; D014570:Urologic Diseases / Q000139:chemically induced
chemical_list: D003606:Dacarbazine; D004317:Doxorubicin; D015080:Mesna; D007069:Ifosfamide