High-Dose versus Low-Dose Cisplatin Chemotherapy plus Treosulfan in Epithelial Ovarian Carcinoma FIGO II–IV: Results of a Prospective Randomized Trial

Abstract

Background: Combination chemotherapies of platinum compounds with alkylating agents have been the standard treatment for patients with advanced ovarian carcinoma over the last decades. The recent development of taxans has added a group of new promising agents; however, long-term results are not yet available. Platin derivates have proven to be an indispensable part in combination chemotherapies for ovarian carcinoma. The dose intensity of cisplatin is, however, still a matter of debate. We report on the long-term results of a prospective randomized trial comparing two dosages of cisplatin combined with treosulfan in patients with advanced epithelial ovarian cancer. Patients and Methods: Between 1988 and 1995, 125 patients with ovarian cancer (FIGO stage II–IV) were randomized to receive 4 cycles (28-day intervals) of either cisplatin 100 mg/m² (high dose, HD) or 50 mg/m² (low dose, LD) in combination with 5 g/m² treosulfan after primary cytoreductive surgery. Postoperative residual tumor was absent in 39 patients (HD: 16; LD: 23), < 2 cm in 61 patients (HD: 36; LD: 25) and > 2 cm in 25 patients (HD: 13; LD: 12). 65 and 60 patients received HD and LD cisplatin, respectively. Second-look surgery was optional. Results:The overall response rate was 70.0% (HD: 70.9%; LD: 68.9%). Pathological complete response (CR) was seen in 45 patients (37.5%), clinical CR in 23 patients (19.2%), partial response (PR) in 16 patients (13.3%), stable disease (SD) in 2 patients, and progression of disease (PD) in 34 patients (28.3%). 5 patients were not assessable for response. Overall median survival was 25.6 (HD: 26.9, LD: 25.2) months. The overall disease-free survival for responders was 19.6 and 24.7 months (HD and LD, respectively). HD chemotherapy did not result in any significant survival benefit in completely resected patients: HD: 39.8 months versus LD: 49.5 months. In suboptimally debulked patients (residual tumor < 2 cm), median survival was 24.1 months (HD) versus 22.6 months (LD). In patients with residual tumors > 2 cm median survival was 14.6 months (HD) versus 15.5 months (LD). Significantly less side effects were seen in the LD group: anemia (p = 0.008); nephrotoxicity (p = 0.014); alopecia (p = 0.017). Conclusions: Our data suggest that LD cisplatin-based chemotherapy is as effective as HD chemotherapy in patients with advanced epithelial ovarian cancer, but is far less toxic.

Toward a myeloablative regimen with clinical potential: II. Treosulfan induces specific skin graft tolerance across haploidentical MHC barriers

“…Treosulfan (L-treitol 1,4-bismethanesulfonate, Ovastat s ) is a water-soluble prodrug of a bifunctional alkylating cytostatic and has mainly been used in the therapy of advanced ovarian cancer. [10][11][12][13] Treosulfan caused only moderate side effects in patients, but these were manageable and rapidly reversible. 13,14 Recently, we have shown that Treosulfan can be used to induce donor-specific tolerance over complete MHC barriers using either T-cell-depleted BMC or hematopoietic stem cells.…”