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The purpose of our study was (i) to evaluate the impact of alltrans retinoic acid (ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged X61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day þ 3 after the initiation of chemotherapy (ATRA-arm, n ¼ 122) or no ATRA (standard-arm, n ¼ 120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n ¼ 31) or 1-year oral maintenance therapy (n ¼ 30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA-and the standard-arm (52 vs 39%; P ¼ 0.05). Eventfree (EFS) and overall survival (OS) were significantly better in the ATRA-compared to the standard-arm (P ¼ 0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (Po0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML.

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The objective of the AML HD93 treatment trial was to evaluate the outcome in young adults with acute myeloid leukemia (AML) after postremission therapy was stratified according to cytogenetically defined risk. The rationales for the study design were based (i) on previous favorable results with high-dose cytarabine in AML with t(8;21), inv/t(16q22) and in AML with normal karyotype, and ii) on encouraging results obtained in several phase II trials using autologous stem cell transplantation (SCT). Between July 1993 and January 1998, 223 eligible patients, 16-60 years of age with newly diagnosed AML other than French-American-British type M3/M3v, were entered into the trial. Risk groups were defined as follows: low risk: t(8;21) or inv/t(16q22); intermediate risk: normal karyotype; high risk: all other chromosomal abnormalities. Following intensive double induction therapy with idarubicin, cytarabine and etoposide, all patients in complete remission (CR) received a first consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). A second consolidation therapy was stratified according to the risk group: low risk: HAM; intermediate risk: related allogeneic SCT or sequential HAM; high risk: related allogeneic or autologous SCT. Double induction therapy resulted in a high CR rate of 74.5%, and 90% of the responding patients were eligible for consolidation therapy. Survival for all 223 trial entrants was 40%, and for the 166 patients who entered CR, disease-free (DFS) and overall survival were 40 and 51% after 5 years, respectively. Within the low-, intermediate-and high-risk groups, DFS and survival after 5 years were 62.5 and 87, 40 and 49 and 17 and 26% respectively, without advantage for allogeneic transplantation in the intermediate-and high-risk groups. Postremission therapy-related mortality was 0, 7 and 14%, respectively. This study demonstrates the feasibility of cytogenetically defined risk-adapted consolidation therapy. The overall trial results are at least equivalent to those of published trials supporting the risk-adapted treatment strategy.

Background. Cardiotoxicity related to the widely used cytotoxic compound 5‐fluorouracil (5‐FU) is rare compared with the frequency observed with the use of anthracyclines. More effective protocols incorporating active biomodulatory compounds like folinic acid (FA) or combination chemotherapy change type and severity of toxicity as well. The objective of the current study was to assess cardiotoxicity of the combination 5‐FU and folinic acid. Methods. The authors' multicenter experience with 390 patients treated for advanced gastrointestinal cancer with intermediate‐dose folinic acid and 5‐FU was reviewed. Results. The overall risk of cardiotoxicity was 3%, which is not significantly higher than that reported with 5‐FU alone. Eight of 53 patients with a history of cardiac disease reported cardiac symptoms (15.1%), compared with 5 of 337 patients (1.5%) with a no history of cardiac disease. Median time to symptoms was 3 days (range, 2–6). Nine patients had symptoms resembling myocardial ischemia, one patient died due to assumed myocardial infarction related closely to fluorouracil treatment, four patients had supraventricular arrhythmia, and one patient had congestive heart failure. A history of cardiac disease was the only risk factor associated with cardiotoxicity. Relapses were frequent on reinstitution of therapy despite cardiac symptoms in the preceding cycle. Therapeutically or prophylactically administered nitrates had no significant effect. Conclusion. Physicians should be aware of the cardiotoxic properties of active fluorouracil treatment. The combination of 5‐FU and leucovorin does not differ from single‐agent therapy in frequency or type of cardiotoxicity. Close monitoring of patients is mandatory, especially for those patients at high risk for cardiac side effects. Treatment should be discontinued if coronary symptoms develop, because neither effective treatment nor prophylaxis exists for such symptoms.