ORAL TROFOSFAMIDE AS MAINTENANCE THERAPY IN ADULT PATIENTS WITH BONE AND SOFT TISSUE SARCOMAS

Reichardt P ⁽¹⁾, Tilgner J ⁽¹⁾, Mrozek A ⁽¹⁾, Hohenberger P ⁽²⁾, Dörken B ⁽¹⁾ (Department of Hematology, Oncology and Tumorimmunology ⁽¹⁾ and Department of Surgical Oncology ⁽²⁾, Robert-Rössle-Klinik, Universitätsklinikum Charité, Humboldt-University, 13122 Berlin; Germany.

Introduction: Combination chemotherapy with anthracyclines and ifosfamide results in approximately 30 to 50 % mostly partial responses in adult patients (pts.) with advanced soft tissue sarcoma. Another approximately 25 % of pts. obtain stable disease. While pts. in complete remission seem to have a prolonged survival, sometimes even durable remissions, partial remissions and disease stabilizations tend to be rather short. Second line treatment options are very limited in bone and soft tissue sarcomas, with high-dose ifosfamide being the only drug with reproducible activity. Again, remissions are mostly partial and of short duration. In order to prolong time to progression, maintenance therapy (MT) might represent an option for patients reaching at least stable disease. Prerequisites for MT are an active drug, preferably orally available with a low toxicity profile and reasonable costs. Trofosfamide (Ixoten ®, ASTA Medica AWD Germany) is an orally available oxazaphosphorine with a very favorable toxicity profile, whose main metabolite is ifosfamide. Activity has been reported in first and second line treatment in soft tissue sarcoma.

Patients and treatment: In a single institution retrospective study, we analyzed 24 pts. (13 males and 11 females, median age 53 years, range 23 to 64), treated with trofosfamide as MT after partial remission (9 pts.) or stable disease (15 pts.) following ifosfamide containing combination chemotherapy or single-agent ifosfamide given as first-line (8 pts.), second-line (11 pts.) or higher line (5 pts.) treatment. Histologies were soft tissue sarcoma in 18 pts. and bone sarcomas in 6 pts. Trofosfamide was given at a daily dose of 100 to 150 mg p. o with dose-adjustment by hematotoxicity. Treatment was continued until documented disease progression.

Results: 19 pts. stopped MT after 2, 3, 3, 3, 4, 4, 4, 5, 7, 7, 9, 10, 10, 11, 14, 15, 18, 21 and 24 months, respectively. 5 pts. are currently on continuous MT for 4+, 8+, 20+, 29+, and 53+ months, respectively. Long lasting disease stabilizations occurred in pts. with both PR or SD following ifosfamide containing first- or second-line regimens. Toxicity consisted only of mild myelosuppression. No other toxicities (neuro, renal, mucositis) occurred. No treatment had to be stopped due to toxicity.

Conclusions: MT with oral trofosfamide offers the opportunity of longer lasting disease stabilizations following first- or second-line chemotherapy in adult pts. with bone and soft tissue sarcomas at reasonable costs and minimal toxicity.