Background: Trofosfamide is a commercially available oxazaphosphorine prodr
ug that requires metabolic activation at the mixed-function oxidase system
of the liver. Metabolic products of trofosfamide include ifosfamide (the ma
jor metabolite) and cyclophosphamide. In pilot studies with trofosfamide at
a dose of 150 mg per day given continuously, significant activity against
refractory small-cell lung cancer and mild toxicity in elderly, pretreated
patients was observed. The prognosis of pretreated elderly patients with me
tastatic lung cancer is extremely poor. Patients and Methods:Thus, the aim
of this trial was to test the activity of a monotherapy with trofosfamide g
iven orally and continuously (3x50 mg daily) in elderly and/or heavily pret
reated patients with small-cell or non-small-cell lung cancer. 51 adult pat
ients (median age 65 years, range 38-77 years) with pretreated (surgery 1,
radiation 11, chemotherapy 33) metastatic (liver 23, lymph nodes 25, bone 7
adrenal gland 4, other sites 17) small-cell lung cancer (n=24) or non-smal
l-cell lung cancer (n=27) received 3x50 mg trofosfamide continuously until
proven tumor progression. Results: All patients survived the therapy. Major
responses have been seen in patients with small-cell lung cancer (CR 5, PR
4, SD 8, PD 7). The median duration of response was 5 months. In patients
with metastatic nonsmall cell lung cancer no major response was observed (S
D 18, PD 9). However, in patients with stable disease under trofosfamide th
erapy normal activity of the patients for averagely 1 year was seen,Trofosf
amide was well tolerated without significant gastrointestinal or renal toxi
city, peripheral neurotoxicity or alopecia. Bone marrow toxicity was the le
ading toxicity (WHO grade II leukopenia and/or thrombocytopenia). Conclusio
n:Trofosfamide seems to be an active agent in the treatment of elderly and/
or pretreated patients with metastatic lung cancer, especially small-cell l
ung cancer.