title: A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors.
abstract: A prospective randomized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin (60 mg/m2 every 3 to 4 weeks) administered by bolus or 72-hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high-grade soft tissue sarcoma of the extremity or superficial trunk. Cardiac toxicity, defined as a 10% or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography, was evaluated in 69 patients. Cardiotoxicity was seen in 61% of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2. Among patients who received continuous infusion, 42% had cardiotoxicity with a median dose of 540 mg/m2. The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm (P = 0.0017). Two patients in each group had clinical congestive heart failure, with one cardiac death occurring in each. There was a trend toward a lower rate of metastasis (P = 0.19) and a significantly lower rate of death of disease (P = 0.036) for patients treated with the bolus dose. Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis: blood transfusion within 24 hours of operation (P less than 0.00001), tumor deep to the fascia and 5 cm or more in size (P = 0.0043), and a histologic subtype other than liposarcoma (P = 0.0002). The unfavorable effect of continuous infusion was not selected in the model (P = 0.16). Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational. Furthermore, the impact of perioperative blood transfusion merits further study.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: E S
authors.initials: ES
authors.lastname: Casper
authors.forename: J J
authors.initials: JJ
authors.lastname: Gaynor
authors.forename: S I
authors.initials: SI
authors.lastname: Hajdu
authors.forename: G B
authors.initials: GB
authors.lastname: Magill
authors.forename: C
authors.initials: C
authors.lastname: Tan
authors.forename: C
authors.initials: C
authors.lastname: Friedrich
authors.forename: M F
authors.initials: MF
authors.lastname: Brennan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000601:surgery; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide