Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia.

In an attempt to improve the complete remission (CR) rates and to prolong the remission duration especially in elderly patients > 50 years of age, we have used a combination chemotherapy of idarubicin (10 mg/m2 IV x 3 days), cytarabine (AraC, 100 mg/m2 CIVI x 7d), and etoposide (100 mg/m2 x 5 days) in combination with granulocyte colony-stimulating factor (G-CSF) priming [5 mg/kg SQ day 1 until absolute neutrophil count (ANC) recovery] for remission induction. Responding patients received two consolidation courses of idarubicin, AraC, and etoposide, followed by a late consolidation course of intermediate-dose AraC (600 mg/m2 IV every 12 h x 5 days) and amsacrine (60 mg/m2 IV x 5 days). A total of 112 patients (57 male/55 female) with a median age of 58 years (range: 22-75) have been entered and are evaluable for response: 19 refractory anemia with excess of blast cells in transformation (RAEB-T), 84 acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS), and 9 secondary AML after chemotherapy/radiotherapy. The overall CR rate was 62%, partial remission (PR) rate 10%, treatment failure 16%, and early death rate 12%. The CR rate was higher in patients < or = 60 years (68 vs 55%), mainly due to a lower early death rate (5 vs 21%, p<0.001). After a median follow-up of 58 months, the median overall survival is 14.5% and median duration of relapse-free survival 8 months. After 60 months, the probability of CR patients to still be in CR and alive is 16% (20% in patients < or = 60 years and 13% in patients >60 years), while the probability of overall survival is 12% (15% in patients < or = 60 years and 9% in patients > 60 years). Compared to our previous trial (AML-MDS Study 01-92) which was done with identical chemotherapy but no G-CSF priming in 110 patients with RAEB-T, AML after MDS, or secondary AML (identical median age, age range, and distribution of subtypes), the CR rate in all patients, as well as CR rate, overall survival, and relapse-free survival in patients > 60 years have significantly been improved. Thus, intensive chemotherapy with G-CSF priming is both well tolerated and highly effective for remission induction in these high-risk patients.

CGS 16949A, a new aromatase inhibitor in the treatment of breast cancer--a phase I study.

Forty-six postmenopausal women with either locally advanced or metastatic breast cancer were treated with the aromatase inhibitor CGS 16949A in three different daily doses (0.3 mg, 0.6 mg and 0.9 mg total daily dose). 41 patients (89%) were pretreated by endocrine treatment for metastatic disease; 30 of these 41 were also pretreated with chemotherapy. Of the remaining 5 patients (11%) 3 were previously treated with chemotherapy alone and 2 were not pretreated. Evaluable sites of disease were: skin and soft tissue (including local recurrence) in 34, bone in 31, lung in 14 and viscera in 13 instances, respectively. 1 PR (3%) and 9 stable diseases (24%) were observed in the 37 patients assessable for response. All but two of these results were observed in the 0.9 mg group. Time to progression was 14 months for the patient showing a PR, and the median time to progression for those with stable disease was 6 months (range 6 to 23 months). Plasma estradiol and estrone levels were measured in patients receiving the daily dose of 0.6 mg (n = 4) and 0.9 mg (n = 15). The estrone levels decreased from a mean of 23.1 pg/mL (SD 17.1) to 10.5 pg/mL (SD 6.6) in the 0.6 mg-group and from 21.2 pg/mL (SD 18.9) to 9.1 pg/mL (SD 5.5) in the 0.9 mg-group within 4 days of drug administration (p less than 0.0001 from baseline in both groups, with no significant difference between doses).(ABSTRACT TRUNCATED AT 250 WORDS)

A multicenter trial of interleukin-2 and low-dose cyclophosphamide in highly chemotherapy-resistant malignancies.

The anti-tumor activity of high-dose recombinant interleukin-2 (IL-2) has been demonstrated in several recent preclinical and clinical studies. In an attempt to study possible synergistic effects with low-dose cyclophosphamide (CYC), a phase II clinical trial was initiated in 32 patients, 18 with malignant melanoma (MM) and 14 with renal cell carcinoma (RCC). The recombinant IL-2 (Cetus Corp., Emeryville, Ca, U.S.A.) was given once daily at 3 x 10(6) U/m2, as a 30-min infusion for 14 days in cycle I and for five days twice in cycles II and III, respectively; if tolerated, the dose was escalated to a maximum of 6 x 10(6) U/m2/day; the cycles, separated by 1-week treatment-free intervals, were each preceded by a single i.v. bolus of CYC at 350 mg/m2. The most prominent side-effects encountered in this trial consisted of a capillary leak syndrome, myalgia and fever requiring dose reduction in half of the patients during the first cycle. Given the limit of tolerable toxicities in a standard care unit, the regimen employed achieved minor anti-tumor activity. No objective responses were achieved in patients with RCC and a 15% remission rate (PR + MR) was seen in melanoma patients.