Morbidity and costs of remission induction therapy with all-trans retinoic acid compared with standard chemotherapy in acute promyelocytic leukemia Journal Article
| Authors: | Eardley, A. M.; Heller, G.; Warrell, R. P. Jr |
| Article 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). For patients who achieved complete remission, the median length of hospital stay during induction was 30 days for the all-trans RA group and 44 days for the chemotherapy group (p=0.002). For all patients, the median cost of hospitalization during induction exclusive of physician charges expressed in constant 1992 dollars was $61756 for the all-trans RA group compared with $97944 for the chemotherapy group (p=0.012). Kaplan-Meier analysis of both relapse-free (p=0.011) and overall survival (p=0.014) significantly favored patients who received all-trans RA for remission induction. Both standard chemotherapy and all-trans RA induce complete remission in a high proportion of patients with APL. Compared to the use of chemotherapy alone, early mortality has not yet been substantially altered by all-trans RA. However, this treatment program that employs all-trans RA alone for remission induction, followed by cytotoxic chemotherapy for consolidation, has improved survival with significantly less morbidity and lower cost. For patients with serious diseases such as cancer, participation In early-stage clinical trials may not only be cost-effective but may also represent state-of-the-art clinical care for these individuals. |
| Keywords: | adolescent; adult; clinical article; controlled study; aged; clinical trial; chemotherapy; cytarabine; controlled clinical trial; morbidity; antifungal agent; retrospective study; fever; drug cost; health care cost; antiinfective agent; acute myeloblastic leukemia; remission; intermethod comparison; erythrocyte; anthracycline; erythrocyte transfusion; retinoic acid; thrombocyte transfusion; patient; human; male; female; priority journal; article |
| Journal Title: | Leukemia |
| Volume: | 8 |
| Issue: | 6 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1994-06-01 |
| Start Page: | 934 |
| End Page: | 939 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 8207987 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- CODEN: LEUKE C2 -- Source: Scopus |
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