title: Morbidity and costs of remission induction therapy with all-trans retinoic acid compared with standard chemotherapy in acute promyelocytic leukemia.
abstract: With the recent pressure to control health care expenditures, the costs of patient participation in clinical trials, especially in their earliest phases, have come under increasingly intense scrutiny. We therefore reviewed our experience in patients with acute promyelocytic leukemia (APL) who were treated during the first US trial of a new experimental drug, all-trans retinoic acid (RA). The purpose of the review was to evaluate parameters of patient morbidity and financial cost associated with the use of all-trans RA compared with standard chemotherapy for induction of complete remission in newly-diagnosed patients with APL. We retrospectively compared outcomes of consecutive patients treated during the first 2 years of our studies that used all-trans RA for remission induction (1990-1992) with an identical number of patients consecutively treated with standard chemotherapy (cytosine arabinoside plus an anthracycline) during the immediately preceding period (1985-1990). Responding patients in both groups received post-remission chemotherapy. Evaluation parameters included transfusions of packed red blood cells and platelets, use of anti-bacterial and anti-fungal drugs, duration of fever, time to remission, length of hospital stay, hospital charges, and both overall and relapse-free survival. Thirty patients were evaluated in each group. Complete remission was achieved in 26 patients (87%) treated with all-trans RA, and 24 patients (77%) treated with chemotherapy (p = 0.5). In the chemotherapy group, there were five early deaths (four from hemorrhage, one from sepsis); one other patient was resistant to treatment and died at 6 months. Four patients in the all-trans RA group died prior to response from complications of the 'retinoic acid syndrome'. The median time to complete response by all criteria was 41 days (range, 18-78) for the all-trans RA group and 50 days (range, 24-121) for patients who received conventional chemotherapy (p = 0.2). Looking only at patients who achieved remission, chemotherapy-treated patients required a significantly greater number of platelet transfusions (medians, 14 vs. 4; p < 0.001) and packed red blood cell transfusions (15 vs. 4; p < 0.001). Patients who received chemotherapy also experienced a significantly larger number of days with fever (13 vs. 6; p = 0.01) that was reflected in a greater median number of days on combination antibiotics (35 vs. 21; p = 0.001) and Amphotericin B (20 vs. 0; p < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021.
authors.forename: A M
authors.initials: AM
authors.lastname: Eardley
authors.forename: G
authors.initials: G
authors.lastname: Heller
authors.forename: R P
authors.initials: RP
authors.lastname: Warrell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics / Q000627:therapeutic use*; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D004358:Drug Therapy / Q000191:economics* / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000191:economics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013997:Time Factors; D014212:Tretinoin / Q000191:economics / Q000627:therapeutic use*
chemical_list: D003561:Cytarabine; D014212:Tretinoin; D015255:Idarubicin; D003630:Daunorubicin