Daily low-dose oral temozolomide as maintenance therapy following doxorubicin plus dacarbazine in advanced leiomyosarcoma patients: An observational study.

Abstract

11559 Background: Doxorubicin (Dox) combined with dacarbazine (DTIC) is a standard first-line regimen for advanced leiomyosarcoma (LMS), but its long-term use is restricted due to potential cardiac toxicity. Although the addition of trabectedin to Dox, followed by trabectedin maintenance, has demonstrated improved overall survival (OS) and progression-free survival (PFS), trabectedin’s limited availability in China poses a significant challenge. Given that both temozolomide (Tem) and DTIC convert to the same active metabolite (MTIC) in the body, we investigated the efficacy of daily low-dose Tem as maintenance therapy following Dox plus DTIC. Here, we present the results of this observational study. Methods: Eligible patients with metastatic or unresectable LMS received up to six cycles of Dox (60-70 mg/m², day 1) or pegylated liposomal Dox (PLD, 35–45 mg/m², day 1) combined with DTIC (0.9–1.2 g/m², day 1) every three weeks. Patients without progression after six cycles of Dox/PLD plus DTIC were transitioned to maintenance therapy with daily oral temozolomide (75 mg/m²). Maintenance Tem was continued until disease progression. The primary endpoint was PFS during maintenance, assessed by investigators. Secondary endpoints included OS and safety. PFS and OS were defined as the time from initiation of oral Tem until disease progression and death, respectively. Results: Between May 2022 and December 2024, 20 patients were enrolled, with a median age of 55 years. All patients were female. The primary tumor site was uterine in 45% of cases and non-uterine in 55%; 90% had metastatic disease, and 10% had locally advanced disease. Seventeen patients were evaluable for efficacy. The median PFS during maintenance was 7.1 months, with three patients achieving disease control for over 12 months. Treatment was generally well-tolerated, with the most common adverse events (AEs) being grade I/II nausea (80%), vomiting (45%), and white blood cell reduction (25%). Serious AEs leading to treatment discontinuation occurred in two patients: one due to severe vomiting and one due to elevated liver enzymes. Conclusions: Daily low-dose oral temozolomide appears to be an effective and well-tolerated maintenance therapy following Dox plus DTIC for patients with advanced LMS. This approach may offer a viable alternative for patients in regions where trabectedin is unavailable.