Pegylated Liposomal Mitomycin C Lipidic Prodrug in Combination With External Beam Radiation Therapy in Patients With Advanced Cancer: A Phase 1B Study

Abstract

To evaluate a formulation of pegylated liposomal mitomycin C lipidic prodrug (PL-MLP) in patients concomitantly undergoing external beam radiotherapy (RT). Patients with metastatic disease or inoperable primary solid tumors requiring RT for disease control or symptom relief, were treated with two courses of PL-MLP (1.25, 1.5 or 1.8 mg/kg) at 21-day intervals, along with 10 fractions of conventional RT or 5 SBRT fractions initiated 1-3 days after the first PL-MLP dose and completed within 2 weeks. Treatment safety was monitored for 6 weeks, and disease status was reevaluated at 6 week-intervals thereafter. MLP levels were analyzed 1h and 24h after each PL-MLP infusion. Overall, 19 patients with metastatic (18) or inoperable (1) disease, received combination treatment, with 18/19 completing the full protocol. Most patients (16) were diagnosed with advanced gastrointestinal tract cancer. One grade 4 neutropenia event possibly related to study treatment was reported; other adverse events were mild or moderate. Of the 18 evaluable patients, 16 were free of radiotherapy target lesion progression at first re-evaluation. Median survival of the entire patient population was 63.3 weeks. Serum MLP level correlated with dose increases and similar long circulating profiles were observed before and after RT. PL-MLP up to 1.8 mg/kg in combination with RT treatment is safe, with a high rate of tumor control. Drug clearance is not affected by radiation. PL- MLP is potentially an attractive option for chemoradiotherapy that warrants further evaluation in randomized studies in the palliative and the curative settings.