A randomized phase II study on the effects of 5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin in patients with relapsed acute leukemia: an EORTC Leukemia Cooperative Group phase II study (06893).

5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin has been applied in a treatment protocol for patients with a relapse of acute myeloid or lymphocytic leukemia. Sixty-three patients received 5-Aza-2'-deoxycytidine 125 mg/m2 as a 6 h infusion every 12 h for 6 days in combination with either amsacrine 120 mg/m2 as a 1 h infusion on days 6 and 7 (n=30) or idarubicin 12 mg/m2 as a 15 min infusion on days 5, 6 and 7 (n = 33). Twenty-three patients (36.5%) obtained a complete remission (CR); eight of 30 patients treated with amsacrine and 15 of 33 treated with idarubicin. Patients with an interval of more than 1 year between initial diagnosis and start of the protocol achieved CR in 51.4%, compared to 15.4% for patients with an interval of less than 1 year. Patients with normal cytogenetics had a higher CR rate (61%) than those with abnormal cytogenetic findings (15.8%). Digestive tract and hematologic toxicity was prolonged, compared to standard induction schedules. Median disease-free survival was approximately 8 months, with only 20% of patients staying in remission for more than 1 year. 5-Aza-2'-deoxycytidine is a good antileukemic agent with considerable toxicity. Current results merit further investigations in previously untreated leukemia.

Compassionate use of tropisetron in patients at high risk of severe emesis.

Tropisetron is a 5-HT3 receptor antagonist which suppresses nausea and vomiting induced by cancer chemotherapeutic agents. In this study, tropisetron was evaluated on a compassionate-need basis in 545 cancer patients who had either proved refractory to antiemetic treatment during previous chemotherapy or who were at high risk of emesis as a result of current therapy. Tropisetron (5 mg or 10 mg) was administered as a 15-minute infusion prior to chemotherapy, with the further possibility of an additional dose, either orally or parenterally, on one or more subsequent days. In some patients the drug was administered orally on the day before treatment. On Day 1 of Course 1, 64.7% of patients had a complete response to tropisetron, i.e. no nausea or vomiting, and 26.9% of patients had a partial response. More than 80% of patients with a complete response in Course 1 had a complete response in Course 2 and of the partial responders in Course 1, 37% achieved a complete response in Course 2. Of the 7.6% failures in Course 1, a further 26% achieved a complete response in Course 2. Tropisetron was well tolerated, with adverse effects recorded in only 45 (8%) patients.

Compassionate use of a 5-HT3-receptor antagonist, tropisetron, in patients refractory to standard antiemetic treatment.

The efficacy of tropisetron in the prevention of nausea and vomiting induced by chemotherapy of varying emetogenic potential was evaluated in 545 patients with a variety of malignancies who had either proved refractory to antiemetic treatment during previous chemotherapy courses or who were considered to be at high risk of nausea and vomiting. Tropisetron 5 or 10mg was administered intravenously just before chemotherapy, with the possibility of additional oral or intravenous doses on the day before chemotherapy and on 1 or more subsequent days. On day 1 of the first course of chemotherapy, a complete response (no nausea and no vomiting) was achieved in 62% of patients and a partial response (1 to 4 vomits and/or episodes of nausea) in 29%. Among the 325 patients who received a second course of chemotherapy, more than 80% of those with a complete response on day 1 of course 1 also had a complete response on day 1 of course 2; 37% and 26%, respectively, of patients with a partial response or failure (1 or more vomits and/or episodes of nausea) on day 1 of course 1 then had a complete response on day 1 of course 2.