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 Journal Article


Authors: Casper, E. S.; Gaynor, J. J.; Hajdu, S. I.; Magill, G. B.; Tan, C.; Friedrich, C.; Brennan, M. F.
Article 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 < 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. Copyright © 1991 American Cancer Society
Keywords: adult; aged; aged, 80 and over; survival rate; major clinical study; doxorubicin; combined modality therapy; neoplasm staging; prospective studies; metastasis; neoplasm recurrence, local; antineoplastic combined chemotherapy protocols; lung neoplasms; drug administration schedule; cyclophosphamide; sarcoma; cardiotoxicity; soft tissue sarcoma; drug toxicity; heart left ventricle ejection fraction; infusions, intravenous; stroke volume; soft tissue neoplasms; injections, intravenous; middle age; heart failure, congestive; prognosis; human; male; female; priority journal; article; support, u.s. gov't, p.h.s.
Journal Title: Cancer
Volume: 68
Issue: 6
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 1991-09-15
Start Page: 1221
End Page: 1229
Language: English
DOI: 10.1002/1097-0142(19910915)68:6<1221::Aid-cncr2820680607>3.0.Co;2-r
PUBMED: 1873773
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 27 September 2019 -- Source: Scopus
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MSK Authors
  1. Murray F Brennan
    1059 Brennan
  2. Ephraim S Casper
    108 Casper
  3. Gordon B. Magill
    30 Magill
  4. Steven I. Hajdu
    80 Hajdu
  5. Jeffrey J. Gaynor
    36 Gaynor