Ly. Dirix et al., A PHASE-II TRIAL OF DOSE-ESCALATED DOXORUBICIN AND IFOSFAMIDE MESNA IN PATIENTS WITH MALIGNANT MESOTHELIOMA, Annals of oncology, 5(7), 1994, pp. 653-655
Background: This study investigated the feasibility and efficacy of do
xorubicin dose-escalated chemotherapy in combination with ifosfamide i
n patients with malignant mesothelioma. Patients and methods: In this
single institution phase II study, 24 chemotherapy-naive, eligible pat
ients were entered. The chemotherapy regimen consisted of doxorubicin
75 mg/m2 in combination with ifosfamide 5 gr/m2 given as a continuous
24 hour infusion, every 21 days with either rhG-CSF (5 mug/kg) or rhGM
-CSF (250 mug/m2) as haematopoietic support from d3 to d14. Cycles wer
e repeated every 3 weeks. Results: We treated 24 patients, of whom 22
are evaluable for tumour response. One of the two inevaluable patients
died from a cerebral haemorrhage during a period of grade III thrombo
cytopenia after the second course. In 7 patients a partial response wa
s observed, resulting in a response rate of 32% (95% confidence interv
al 13%-51%). Median response duration was 6 months (range 1-13) and me
dian survival was 7 months (range 1-18). Conclusions: The high-dose re
gimen with growth factor support is feasible in this group of patients
and leads to an interesting response rate. The limiting toxicity for
further dose increments and more courses of treatment, was cumulative
thrombocytopenia. There seems to be a subgroup of patients with malign
ant mesothelioma which is less susceptible to develop thrombocytopenia
. However, the overall toxicity and the poor response duration limit t
he use of this schedule in the treatment of malignant mesothelioma.