Phase II study of temozolomide and thalidomide in patients with unresectable or metastatic leiomyosarcoma

Abstract

We assessed the efficacy of combined temozolomide and thalidomide in patients with unresectable or metastatic leiomyosarcoma in a phase II single-institution trial. Twenty-four patients were enrolled. Temozolomide (150 mg/m 2 /day for 7 days every other week) was administered with concomitant thalidomide (200 mg/day), and continued until unacceptable toxicity or disease progression. There were no complete responses and two (10%) partial responses. Five patients (24%) had stable disease for at least six months. Fourteen patients (67%) progressed after a median of two-month treatment. The median overall survival (twenty-two assessable patients) was 9.5 months [95% CI 7-28 months]. There were no treatment-related deaths or CTC grade 4 toxicities. Thirteen patients were dose-reduced or discontinued thalidomide due to toxicity. In conclusion, this combination of temozolomide and thalidomide provided disease stabilization in a subset of patients with advanced leiomyosarcoma. We hypothesize that temozolomide is the active agent in this regimen, and should be further studied.

Management of advanced uterine leiomyosarcoma

“…Although the combinations of doxorubicin plus ifosfamide [28] and doxorubicin plus dacarbazine [25] both had higher response rates (30% and 25%, respectively) compared with doxorubicin alone, these combinations have not improved overall survival and are associated with more toxicity. The response rate of temozolomide (at multiple doses and schedules) in uterine and extrauterine LMS has ranged between 4 and 33% across several prospective and retrospective studies [39][40][41][42]. Single agent dacarbazine had an 8-18% response rate across all types of soft tissue sarcoma, but has not been studied specifically in uterine LMS [37,38].…”

Management of sarcomas of the uterus

“…Mesna, doxorubicin, ifosfamide and dacarbazine resulted in a 39% response rate and was well tolerated with only 4% of cycles delayed for toxicity [28]. TMZ and thalidomide demonstrated a 10% RR [32]. They demonstrated a significant improvement in PFS from 41 to 55% with the addition of chemotherapy, though there was no benefit in OS at 3 years [29 & ].…”

Targeting NF-κB and HIF-1 Pathways for the Treatment of Cancer: Part I

“…The use of lowdose thalidomide either as a monotherapy, or as a supplement for docetaxel treatment of prostate cancer patients, has shown efficacy in reducing the prostate-specific antigen levels (Figg et al 2001). In higher doses, thalidomide has shown positive effects for stabilization of advanced leiomyosarcoma when combined with the alkylating agent temozolomide (Boyar et al 2008). However, the benefit from using thalidomide in patients with endometrial cancer, either recurrent or refractory to routine chemotherapeutic regimens, was only very limited (McMeekin et al 2007).…”