Two Oral Trofosfamide Schedules in Elderly Patients with Refractory Non-Hodgkin‘s Lymphoma

Abstract

Trofosfamide (TROFO) is an orally taken oxazaphosphorine prodrug. Other metabolic products of TROFO include ifosfamide and cyclophosphamide. In pilot studies with TROFO, significant activity against refractory non-Hodgkin’s lymphoma (NHL) and mild toxicity were reported. The prognosis of pretreated elderly patients is extremely poor. Thus, the aim of this trial was to test the activity of single TROFO therapy given orally continuously (c) (3 × 50 mg daily) versus intermittently (i) (300–400 mg daily for 4 days every 21 days) in pretreated elderly patients with refractory NHL. Forty-four patients (25 female, 19 male), median age 69 years (range 65–84) have been accrued to receive either TROFOi or TROFOc. Twenty-seven patients presented with low-grade, 17 with high-grade NHL. All patients had stage III or IV disease, and 12 (27%) were suffering from B symptoms. The majority (41/44, 93%) was heavily pretreated with 2 or more prior regimens (median = 2; range 1–4), 24 had already received other oxazaphosphorine prodrugs. Major responses have been seen in 48% so far, with 3 complete (2 in high-grade) and 18 partial (6 in high-grade) remissions. With TROFOi, responses were seen in 9/21 patients after a median of 3 cycles, with TROFOc in 12/23 patients after a median of 9 weeks. The median duration of response was 4 months in both groups. TROFO was well tolerated in both groups without significant gastrointestinal or renal toxicity, peripheral neurotoxicity or alopecia. Bone marrow toxicity was slightly more pronounced in TROFOc with 57% of WHO grade III leukopenia and/or thrombocytopenia as compared with 43% in TROFOi. Other adverse effects included mild to moderate fatigue, nausea, diarrhea, and vomiting and were seen in a total of 35 patients. TROFO seems to be an active agent in the treatment of elderly pretreated patients with refractory low-grade and high-grade NHL, with responses in about 50% of patients. TROFO is equally effective as TROFOi but is more toxic.