Docetaxel monotherapy in heavily pretreated metastatic breast cancer: a multicenter, community-based feasibility trial.

PURPOSE: To evaluate the efficacy and safety of docetaxel in heavily pretreated and anthracycline-resistant patients with metastatic breast cancer in an outpatient setting. PATIENTS AND METHODS: Between February 1996 and June 1998, 98 consecutive patients who had progressed during or relapsed following prior anthracycline-containing chemotherapy were enrolled into the trial. Docetaxel was administered at a dose of 100 mg/m2 by intravenous infusion every 3 weeks. The administration of colony-stimulating factors was at the discretion of the attending physician. Premedication with dexamethasone was mandatory for all patients. RESULTS: Of the 98 patients, 93 were evaluable for toxicity and response. Patients had received two palliative regimens (median, range 1-5) prior to docetaxel treatment. The most frequent toxicity observed was leukopenia grade III and IV (WHO grading system) which occurred in 47% of patients (grade IV only in 14%). Except for alopecia grade III (64% of patients), nonhematologic side effects grade III-IV were rare (1-7% of patients) and included nausea, stomatitis, diarrhea, peripheral neuropathy, fluid retention and pulmonary toxicities. There were no treatment-related deaths. Objective responses occurred in 40% of patients (CR 6%, PR 34%), and stable disease in 38% of patients. The median duration of response was 5.3 months (range 0.7-18.1 months) while the median survival was 15 months (range 2 36 months). CONCLUSION: Docetaxel is a highly active agent in patients with anthracycline-resistant metastatic breast cancer, even in heavily pretreated patients, with moderate toxicity.

Monitoring of minimal residual disease in patients with MLL-AF6-positive acute myeloid leukaemia by reverse transcriptase polymerase chain reaction.

We studied 210 unselected patients with acute myeloid leukaemia (AML) for MLL abnormalities. Twenty-seven patients (13%) with rearranged MLL genes were identified by means of Southern blot analysis. An MLL-AF6 fusion transcript was detected in six patients by a reverse transcriptase polymerase chain reaction (RT-PCR) for the MLL-AF6 translocation. Sequence analysis showed fusion of MLL exon 7 as well as exon 6 (two patients) or MLL exon 6 as well as exon 5 (four patients) to AF6 exon 2. In only three patients could the t(6;11) also be identified by cytogenetic and/or fluorescence in situ hybridization (FISH) analysis. The MLL-AF6-positive patients were monitored by RT-PCR for a period of 6-33 months. Complete haematological remission (CR) was achieved in all six cases, but was short in 5/6 patients (range 2.6-8.3 months). In these five patients, the MLL-AF6 transcripts were detected in every sample tested after induction and consolidation chemotherapy. One patient received autologous bone marrow transplantation (BMT) which also did not lead to PCR negativity. Intensive salvage therapy was unable to induce a second remission in the relapsed patients. One of the six MLL-AF6-positive patients achieved a molecular CR. He is still in CR at 33 months after diagnosis. Survival analysis indicates a poor prognosis in MLL-AF6-positive patients. The median event-free survival was 6.8 months, the median overall survival 15 months. Persistent PCR positivity was consistently associated with relapse. Thus, RT-PCR provides a valuable and sensitive tool for the identification of t(6;11)-positive AML and the monitoring of response to treatment in these patients. The results of RT-PCR may be useful to evaluate therapeutic procedures and to make treatment decisions, which will enable molecular remissions to be achieved and improve the clinical outcome in this group of patients.