Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group

Abstract

ObjectiveThis report provides follow-up progression-free survival (PFS) and median survival data for women who achieved clinical complete remission (cCR) from stage III ovarian cancer after first-line therapy and were treated with altretamine consolidation therapy.MethodsPatients who enrolled in the SWOG 9326 study from September 1993 to July 1997 were required to have documented cCR from stage III ovarian cancer following front-line platinum-based therapy. Treatment consisted of 6 months of oral altretamine at 260 mg/m2/day for 14 consecutive days of a 28-day cycle.ResultsNinety-seven of 112 enrolled patients were evaluable for efficacy. This report presents median 6.2-year follow-up, dating from study registration. Median PFS was 28 (95% CI: 19–43) months. Median PFS for patients with optimal disease was 45 (95% CI: 27–48) months and for patients with suboptimal disease was 17 (95% CI: 12–26) months. Twenty-six of 61 (43%) patients with optimally debulked lesions and 5 of 36 (14%) patients with suboptimally debulked lesions remained disease free. Median survival of patients with optimally debulked disease has not been reached; median survival of patients with suboptimally debulked disease was 39 (95% CI: 19–51) months. No treatment-related adverse events were reported during the follow-up period.ConclusionsConsolidation therapy with oral altretamine was generally well tolerated and associated with prolonged progression-free and overall survival in the Phase II setting.

Phase III Trial of Intraperitoneal Therapy With Yttrium-90–Labeled HMFG1 Murine Monoclonal Antibody in Patients With Epithelial Ovarian Cancer After a Surgically Defined Complete Remission

“…For example, administration of 6 months of oral hexamethylmelamine to a group of women in a clinical complete response led to a 28-month disease-free survival. 17 Administration of IP platinum to a group of women with a negative second-look laparotomy was also associated with a long disease-free period. 18 All of these trials were single armed and, hence, cannot exclude selection bias.…”

Orchestrated Action of AMPK Activation and Combined VEGF/PD-1 Blockade with Lipid Metabolic Tunning as Multi-Target Therapeutics against Ovarian Cancers

“…Similar synergizing effects of ferroptosis induction in combination with common therapeutic agents have gradually been reported, for example, pre-treatment of Erastin followed by Cisplatin-induced cell death in a variety of cancer cell lines [ 135 ]. Furthermore, Altretamine, an inhibitor of GPX4 lipid repair activity, has already been exploited in ovarian cancer treatment that exhibited ferroptosis initiation and showed well tolerance and associated with prolonged PFS and OS in Phase II clinical study [ 122 , 136 , 137 ]. Therefore, it should be optimistic about the upcoming management of ovarian cancer that promising translational anti-cancer strategies would be developed, and novel combination remedies based on FITs would be helpful to improve patient outcomes.…”

Ferroptosis in Cancer Immunotherapy—Implications for Hepatocellular Carcinoma

“…Pharmacokinetic and toxicity analysis revealed a great inter-and intrapatient variability regarding bioavailability of oral altretamine [175]. Altretamine has been applied in ovarian cancer, including a phase II study showing ferroptosis induction, and was generally well tolerated and associated with prolonged progression-free and overall survival [176,177].…”