Oral Trofosfamide in Elderly and/or Heavily Pretreated Patients with Metastatic Lung Cancer

Abstract

Background: Trofosfamide is a commercially available oxazaphosphorine prodrug that requires metabolic activation at the mixed-function oxidase system of the liver. Metabolic products of trofosfamide include ifosfamide (the major 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 metastatic lung cancer is extremely poor. Patients and Methods: Thus, the aim of this trial was to test the activity of a monotherapy with trofosfamide given orally and continuously (3 ?50 mg daily) in elderly and/or heavily pretreated patients with small-cell or non-small-cell lung cancer. 51 adult patients (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-small-cell lung cancer (n = 27) received 3 ?50 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 non-small cell lung cancer no major response was observed (SD 18, PD 9). However, in patients with stable disease under trofosfamide therapy normal activity of the patients for averagely 1 year was seen. Trofosfamide was well tolerated without significant gastrointestinal or renal toxicity, peripheral neurotoxicity or alopecia. Bone marrow toxicity was the leading toxicity (WHO grade II leukopenia and/or thrombocytopenia). Conclusion: Trofosfamide seems to be an active agent in the treatment of elderly and/or pretreated patients with metastatic lung cancer, especially small-cell lung cancer.