A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).

The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients >/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.

Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).

Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.

Treatment of acute myeloblastic leukemia in adults. The GOELAM experience.

The GOELAM group conducted 2 consecutive trials on the treatment of de novo acute myeloblastic leukemia (AML) in adults. In the GOELAM1 protocol 786 patients aged 15-65 were randomized between two induction treatments (ARA-C 200 mg/m2/day for 7 days plus either Idarubicin 8 mg/m2/day for 5 days or Rubidazone 200 mg/m2/day for 4 days). Out of 731 evaluable patients, 521 (71%) achieved complete remission (CR) without significant difference between the 2 anthracyclines. For patients aged 51-65, the CR rate was significantly higher with Idarubicin (75%) than with Rubidazone (61%) (p = 0.03). In this group of patients the post-remission therapy consisted in only one course of high dose ARA-C plus m-Amsa and the 6 year disease free survival (DFS) was 24% (intention to treat analysis). For patients aged 15-50 years, the post remission therapy was either allogeneic bone marrow transplantation (BMT) (patients up to 40 years of age with an HLA identical sibling) or a first course of intensive consolidation chemotherapy (ICC) followed by a randomization between autologous unpurged bone marrow transplantation (ABMT) and a second course of ICC. There was no significant difference in the 4 year DFS between allogeneic BMT (42%) and the other types of intensive post remission-therapy (40%). The 4 year DFS was 42% for ABMT and 38% for ICC (p = 0.46) (intention to treat analysis). However the median duration of thrombocytopenia was much longer after ABMT (109.5 days versus 18.5 days p = 0.0001). The GOELAM SA3 randomized placebo-controlled protocol tested the impact of GM-CSF given during and after induction treatment for elderly patients (55-75 years). In this study, 232 evaluable patients received induction chemotherapy (Idarubicin 8 mg/m2/day for 5 days plus ARA-C 100 mg/m2/day for 7 days) plus placebo or GM-CSF 5 micrograms/kg/day from day 1 until the end of neutropenia. The CR rate was 61.5%. The median duration of neutropenia was shorter in the GM-CSF arm (22 days versus 27 days p = 0.0001). There was no overall significant advantage for the GM-CSF arm, in terms of CR rate and survival. However for patients age 55-64 the 2 year DFS was significantly higher in the GM-CSF arm (43% vs 17% p = 0.0013).

Treatment of acute myelogenous leukaemia in patients aged 50-65: idarubicin is more effective than zorubicin for remission induction and prolonged disease-free survival can be obtained using a unique consolidation course. The Goelam Group.

From December 1987 to June 1992, 251 patients aged 50-65 with de novo acute myelogenous leukaemia (AML) were recruited to a multi-institutional randomized clinical trial. Induction therapy consisted of Ara-C (200 mg/ m2, continuous infusion, days 1-7) with either zorubicin (ZRB) (200 mg/m2, i.v., days 1-4) or idarubicin (IDR) (8 mg/ m2, i.v., days 1-5). Consolidation therapy consisted of a single course of intensive chemotherapy with high-dose Ara-C (3 g/m2, 3 h infusion, q 12 h, days 1-4) and m-Amsa (100 mg/m2/d, i.v., days 5-7). The complete remission (CR) rate was (73%) with Ara-C/ IDR versus (60%) with Ara-C/ZRB (P = 0.033). In multivariate analysis, factors found to be significant in predicting CR were normal karyotype and treatment with IDR. With a median follow-up of 73 months, the median disease-free survival (DFS) duration of all CR patients and the probability of CR at 6 years were 17 months and 29%. In multivariate analysis the only factor associated with an increased DFS duration was a normal karyotype. The median event-free survival (EFS) duration for all evaluable patients and the median overall survival duration for all eligible patients were respectively 7 and 12 months without any difference between induction arms. The study shows that in patients aged 50-65 idarabicin is more effective than zorubicin for remission induction. However, the type of anthracycline did not influence overall survival duration. Using a unique consolidation course, we observed a prolonged DFS which compares favourably with results obtained with more prolonged consolidation therapy or maintenance treatment.

Idarubicin and high dose cytarabine: a new salvage treatment for refractory or relapsing non-Hodgkin's lymphoma.

Twenty three patients with relapsing (n = 11) or refractory (n = 12) non-Hodgkin's lymphoma (NHL) to one or two prior anthracycline based combination chemotherapy regimens were treated as second or third line regimen with 3 induction cycles of Idarubicin (IDA) (7 mg/m2/d i.v. d1-d3) and high dose cytarabine (HD Ara-C) (1 g/m2/12 h i.v. d1-d3), each cycle was repeated every 3 weeks. Responding patients received a maintenance therapy with monthly cycles of IDA: 15 mg/m2 d1-d3, Etoposide 100 mg/m2 d1-d3, both by oral route. Twenty two patients are evaluable and we observed 13 CR and 1 PR with an overall response rate of 61% (14/23: 95% Cl = 38.5% 80.3%). The median time to progression was 32 months (6.5 - 63 + m.). The response rate to IDA-HD Ara C was not different for patients with (n = 14) or without (n = 9) objective response to the last prior therapy. The main toxicity was hematological: all patients experienced grade 4 neutropenia and 22 patients had grade 4 thrombopenia, but there were no toxic deaths. IDA and HD-Ara-C combination is highly effective in refractory or relapsed. NHL. As hematological toxicity was the limiting factor for further escalation of dose-intensity, further studies might include hematopoietic growth factors support in the therapeutic scheme.

A prospective randomized trial of idarubicin vs daunorubicin in combination chemotherapy for acute myelogenous leukemia of the age group 55 to 75.

A prospective randomized study was conducted comparing the efficacy and toxicity of two anthracyclines for the treatment of patients with acute myeloid leukemia (AML) between 55 and 75 years. A total of 220 patients were randomized to receive as induction chemotherapy cytosine arabinoside (Ara-C: 100 mg/m2/day; continuous infusion for 7 days) combined with either daunorubicin (DNR: 50 mg/m2/day, i.v. bolus for 3 days) (n=108) or idarubicin (IDA: 8 mg/m2/day, i.v. bolus for 5 days) (n=112). The complete remission (CR) rate was similar (P=0.296) after IDA (76/112; 68%) and DNR (66/108; 61%) (P=0.3). For patients aged 55-65, the CR rate was significantly higher after IDA (39/47; 83%) than after DNR (29/50; 58%) (P=0.007). Persistent leukemia was more frequent after DNR (26/108) than after IDA (13/112; P=0.015). Hematological and extra-hematological toxicities were similar. The CR patients were given a consolidation course of chemotherapy with Ara-C: 50 mg/m2/12 h, subcutaneously for 5 days, combined with either DNR:30 mg m2/day, i.v. bolus for 3 days or IDA:8 mg/m2/day i.v. bolus for 3 days according to the initial randomization, and then received a continuous maintenance treatment for 2 years. The survival and disease-free survival (DFS) were similar in both groups; there was no difference in the risk of relapse. However, there was a trend for a longer event-free survival (EFS) in the IDA group than for the DNR patients (P=0.07). Our results seem to indicate that IDA is probably more efficient than DNR for AML patients between 55 and 75 years, and confirm the data published in other studies comparing prospectively IDA and DNR in adults.

Vinorelbine (Navelbine) in the treatment of breast cancer: the European experience.

Phase II studies of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) have been conducted mainly at a dose of 30 mg/m2/wk, and this schedule has been used extensively in the treatment of advanced breast cancer. Vinorelbine used in a first-line setting as a single agent in 25 patients with previously untreated advanced metastatic breast cancer produced objective responses in 15 patients (60%) and complete responses (CR) in five (20%). A large multicenter study to assess the response rate by the main site of disease involvement included 145 assessable patients. The overall response rate was 41% (10 CRs and 50 partial responses: skin, 70%; lymph nodes, 67%; primary tumor, 56%; lungs, 33%; measurable bone, 27%; and liver, 23%). The median time to disease progression was 25 weeks and the median overall survival duration was 18 months. Neutropenia was the principal toxicity with grade 3/4 suppression noted; however, this was not accompanied by serious infection (incidence of grade 3/4 infection < 1%). Other grade 3/4 toxicity also was uncommon. Another phase II study included 50 patients assessable for toxicity and response. The overall response rate was 50% (2% CRs). In a salvage setting (second- and third-line treatment), 33 patients were treated with an overall response rate of 30% (two CRs). Rates of toxicity were no greater than in first-line patients. The most notable results for combination vinorelbine therapy were with a schedule of vinorelbine 25 mg/m2 on days 1 and 8 and doxorubicin 50 mg/m2 on day 1, with cycles repeated every 21 days. The overall response rate for the 89 evaluable patients was 74% (19 [21%] CRs; 47 [53%] partial responses). These data indicate that vinorelbine is a highly active agent with a favorable toxicity profile in the treatment of breast cancer.

Inflammatory breast cancer. Pilot study of intensive induction chemotherapy (FEC-HD) results in a high histologic response rate.

Between July 1988 and May 1990, we treated 45 women with newly diagnosed, unilateral, nonmetastatic, inflammatory breast cancer with an intensive neoadjuvant chemotherapy regimen (FEC-HD) repeated every 21 days, followed by surgery or radiation therapy. Evaluation of efficacy performed 3 to 4 weeks after at least 2 cycles showed disappearance of inflammatory signs in 91% of the patients and improvement in the remaining 9%. With regard to primary tumor and lymph nodes, there were 13 (28.9%) clinical complete responses, 30 (66.6%) partial responses, and 2 (4.5%) without change. No progressive disease was observed. Hematologic toxicity from this regimen was high with grade 4 neutropenia observed at day 14 in 100% of the patients. Retreatment at day 21 was possible in 83% of the cycles. Grade 1 or 2 infections occurred in 102 cycles out of 176 (57.9%). Grade 3 infections were seen in 9 cycles (5%). No septicemia or septic shock occurred. No toxic death occurred. After induction chemotherapy, locoregional treatment consisted of modified radical mastectomy in 39 patients and radiotherapy alone in 6. The mastectomy specimen showed no residual invasive tumor (primary tumor and lymph nodes) in 10 cases (25.6%). Two patients judged as partial responders were in fact histologic complete responders. The clinical and histological response rates observed appeared very promising. For this reason we are currently testing FEC-HD with or without GCSF in a randomized multicenter trial with correction of neutropenia, disease-free survival, and overall survival as main end points.

Pharmacokinetics and metabolism of 4'-iodo-4'-deoxy-doxorubicin in humans.

PURPOSE: 4'-iodo-4'-deoxydoxorubicin is a new anthracycline that currently is under clinical evaluation. To improve the management of future trials, we have determined its pharmacokinetics and metabolism during a phase I/II study and have tried to relate the parameters obtained to the hematologic toxicity of the drug in terms of the survival of blood cells. PATIENTS AND METHODS: The pharmacologic study included 19 patients who were entered at dose levels that ranged between 6 and 90 mg/m2; nine patients were treated at 80 mg/m2, which is close to the maximum recommended dose level. Blood sampling was performed from the end of the bolus infusion to 48 hours after treatment. Drug and metabolites were extracted and analyzed by high-performance liquid chromatography (HPLC), and the data were processed by nonlinear fitting to multicompartment models. RESULTS: Plasma concentrations were best fitted to a three-compartment model with half-lives of 5.2 minutes, 0.79 hours, and 10.3 hours. The total body clearance and volume of distribution at steady state were high (350 L/h/m2 and 2,065 L/m2). The drug was metabolized extensively to a 13-dihydroderivative, 4'-iodo-4'-deoxy-doxorubicinol; the mean area under the curve (AUC) ratio metabolite/parent drug was the highest observed ever for an anthracycline (12.1 +/- 7.4); the metabolite was cleared from the plasma with an elimination half-life of 15.3 hours. The AUCs of the parent compound and its metabolite were related linearly to the dose administered, and showed no saturation phenomenon. Urinary excretion was studied in nine patients and showed a cumulative elimination of less than 6% of the dose administered, two thirds of which were eliminated in the first 12 hours after injection. Ninety-three percent to 100% of the elimination of fluorescent compounds occurred in the form of the metabolite. Drug concentration in five tumor samples showed a rapid uptake of the drug from plasma and a preferential uptake of the parent drug compared with the metabolite. Blood cell counts after 4'-iodo-4'-deoxydoxorubicin treatment showed significant correlations among the surviving fractions of both granulocytes and platelets and the AUCs of the parent drug and its metabolite; the most significant correlations were obtained for the granulocytes and the metabolite. Significant correlations between AUCs and blood-cell survivals were maintained, even if only the nine patients treated at the dose of 80 mg/m2 were taken into account for the computation. CONCLUSIONS: Our results especially show that myelosuppression that is induced by 4'-iodo-4'-deoxydoxorubicin can be well predicted by the measure of the AUC of the drug and its metabolite. This could be used for the further development of the drug toward high-dosage schedules.

Comparative pharmacokinetic study of idarubicin and daunorubicin in leukemia patients.

We have studied the pharmacokinetics of idarubicin and daunorubicin in a total of 16 leukemic patients treated with one of these drugs associated with aracytine. The AUCs obtained for unchanged drugs were proportional to the dose, and the dose-independent pharmacokinetic parameters were very similar for the two drugs: total plasma clearance (39.0 L/h/m2 for idarubicin versus 38.6 for daunorubicin), total volume of distribution (1756 versus 1725 L/m2) and elimination half-life (42.7 versus 47.4 h). The only metabolites detected were the 13-dihydroderivative of each drug, idarubicinol or daunorubicinol. The elimination half-life of idarubicinol was two times higher than that of daunorubicinol (80.7 versus 37.3 h) which provided an AUC ratio metabolite/parent drug higher for idarubicin than for daunorubicin. In view of the fact that idarubicinol is a much more active metabolite than daunorubicinol, this protracted half-life metabolite can account for the reported higher activity of idarubicin as compared to daunorubicin.

Improved bioavailability of a new oral preparation of medroxyprogesterone acetate.

Medroxyprogesterone acetate (MPA) is widely used in the hormonal therapy of breast cancer. So far, oral formulations of MPA commercially available present a very low bioavailability, with a less than 10% extent of oral absorption. A new oral preparation of MPA has been recently developed. Based on a pilot study, an open, randomized, crossover trial has been performed on 22 breast and endometrial cancer patients to evaluate the relative bioavailability of this new oral formulation (200-mg sachet, twice daily) as compared with a standard formulation (Farlutal, 500-mg tablet, twice daily). The bioavailability evaluation was mainly based on the area under the curve measured between two administrations at steady state, after 15 days of continuous therapy. Wide interpatient variability of MPA plasma levels after oral MPA administration was confirmed. The MPA plasma levels were higher in patients treated with the new formulation than in patients treated with Farlutal. The relative bioavailability of the new preparation was 3.5 times higher than that of the standard. This new formulation represents a great improvement in the extent of oral absorption of MPA and could lead to better management of hormone-responsive tumors by hormonal therapy.

Oral idarubicin and low dose cytarabine as the initial treatment of acute myeloid leukemia in elderly patients.

Idarubicin (IDR) is an anthracycline that can be administered orally. Low dose cytarabine (LDARAC) has been commonly used in the treatment of acute myeloid leukemia (AML) in elderly patients. A comination of oral IDR (20 mg/m(2) for 3 days) and LDARAC (10 mg/m(2) q12 hours for 10 days) was given in 32 patients aged 65 to 82 years (median 76) with de novo AML. Eight patients whose marrow remained blastic by day 20 received a second course (IDR for 2 days and LDARAC for 5 days). Complete remission (CR) was achieved in 13 cases (40.5%), (one course 12, two courses 1). There was 1 early death, 3 deaths in aplasia, 2 partial remissions and 13 failures. All but 5 patients were entirely managed in hospital. The median duration of neutropenia was 18 days and only 1 patient obtained CR without therapeutic aplasia. The extrahematologic toxicity was mild with 3 reversible cardiac events. These results are comparable to those obtained with conventional chemotherapy and this regimen could be proposed as induction treatment of AML in elderly patients.

Phase II study of oral idarubicin in elderly patients with advanced breast cancer.

Thirty-one elderly patients with measurable advanced breast cancer entered this phase II study. A dose of 15 mg/m2/day of Idarubicin (IDA) for 3 consecutive days every 3 weeks was given orally. Mean total cumulative dose of IDA received was 175 mg/m2 (range: 45-475 mg/m2). Mean number of cycles given was four (range: 1-15). Out of 27 evaluable patients, three achieved a complete response (CR), four had a partial response (PR) (CR + PR = 26 +/- 17%), nine showed no change, and 11 had a progressive disease. Median time to progression was 83 days (range: 19-728 days). Out of 26 patients evaluable for toxicity, hematologic toxicity at day 21 was moderate: neutropenia grades 3 and 4 = 16% of cycles: two patients had grade 1 thrombopenia; and three patients, grade 3. No cumulative hematologic toxicity was detected. Nonhematologic toxicities consisted of nausea and vomiting in 72% of patients [World Health Organization (WHO) grades 3 and 4 = 8%)] and alopecia in 76% (WHO grades 2-3 = 38%). Grade 1 stomatitis occurred in 4% of cycles. Chemotherapy was discontinued in one patient because of drop of left ventricular ejection fraction (LVEF) from 0.62 to 0.44 at a cumulative IDA dosage of 322 mg/m2. The results of this study show that IDA is an active drug in elderly patients with advanced breast cancer. Due to its simplicity of administration IDA deserves further investigations in combination with other drugs.

Pharmacokinetics of idarubicin after oral administration in elderly leukemic patients.

We have studied the plasma pharmacokinetics of idarubicin (4-demethoxy daunorubicin) in 11 elderly patients suffering from acute myeloblastic leukemia receiving orally 30 mg/m2 per day for 3 consecutive days. Idarubicin culminated in plasma 4 hr after administration and followed three similar time courses after the three administrations. Idarubicinol (13-dihydro-4-demethoxy daunorubicin) was the only fluorescent metabolite in plasma and no aglycone could be detected; idarubicinol concentration was always higher than that of unchanged idarubicin. Due to its protracted half-life (64 hr in this study), this metabolite progressively accumulated and the ratio of the areas under the curve (0-24) idarubicinol/idarubicin increased from day to day. By comparison to results obtained after i.v. administration of the drug in another study, the bioavailability of idarubicin alone can be estimated to about 21%, whereas the bioavailability of the sum idarubicin + idarubicinol is about 41%.

Phase II trial of idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. The Clinical Screening Group of the European Organization for Research and Treatment of Cancer.

A phase II trial of idarubicin (IDR-4 demethoxydaunorubicin) was carried out in patients with advanced breast cancer. A dose of 45 mg/m2 was given orally once every 3 weeks. A total of 66 eligible patients were entered into the trial, 56 of whom were evaluable for response (65 were evaluable for toxicity at least). Therapeutic activity was demonstrated with an overall objective response rate of 21% (95% CI: 11-32%). When used as a first-line treatment, the response rate was 33% (95% CI: 9-57%) but this dropped to 17% when the treatment was administered after chemotherapy. Nausea-vomiting was the most frequent and severe non-hematological toxicity observed (WHO grade 3-4: 29%). Loss of hair was noticed in 48% of the patients but only 4% suffered from complete alopecia. Moderate myelotoxicity was reported but no cardiac dysfunction was noticed. IDR could be very advantageous as compared to other anthracyclines, due to its simplicity of administration associated with the lack of risk of extravasation or chemical phlebitis and also the possibility of it being able to reduce cardiotoxicity. Even if the equiefficacy of IDR and DXR has not, as yet, been clearly demonstrated, IDR should be chosen with preference to DXR when administration is not suitable.

Treatment of acute myeloid leukemia in elderly patients with oral idarubicin as a single agent.

Idarubicin (IDR) is a new anthracycline that can be administered orally. Oral IDR was given at a dose of 30 mg/m2 daily for 3 d in 20 patients aged 65 to 79 yr with previously untreated acute myeloid leukemia (AML). 5 patients whose marrow remained blastic at d 14 received a second course. 8 patients achieved complete remission (6 after one single course). There were: 1 early death, 4 deaths in aplasia, 7 failures. The hematologic toxicity was high. All but 1 patient had to stay in hospital and the duration of neutropenia was 12 to 34 d (median 19). Oral IDR is an effective therapy for AML in elderly patients but the total dose of 90 mg/m2 is too aggressive to be administered safely outside the hospital.