Targeted radiopharmaceutical therapy for advanced lung cancer: Phase I trial of rhenium Re188 somatostatin analogue P2045

Abstract

7672 Background: Both small cell (SCLC) and non-small cell lung cancer (NSCLC) overexpress somatostatin receptors (SSTR). P2045 peptide is an 11-amino acid somatostatin analogue that binds with high affinity to SSTR. The analogue can be labeled with Tc-99m to gauge receptor prevalence, or with Re-188 for 2.1MeV beta radiotherapy. To evaluate the safety of this approach a phase I dose-escalation study of Re-188 P2045 in SSTR positive lung cancer was performed. Methods: Patients (pts) were required to have progressive advanced lung cancer, PS 0–1, and normal organ function. There were no limitations on the number of prior therapies. Tumor SSTR was detected with Tc-99m P2045. If positive, treatment with escalating doses of Re-188 P2045 was instituted. Three doses were evaluated, 30 mCi/m2, 60 mCi/m2 and 90 mCi/m2. A single dose of Re-188 P2045 was allowed. Dose limiting toxicity was defined as ≥ grade 3 non-hematologic toxicity, grade 4 hematologic toxicity or projected renal radiation dose of >20 Gy. Results: 15 pts entered, 7 M, 8 F, median age 61y, 9-PS0, 6 PS1. 13 NSCLC, 2 SCLC. 14 pts had ≥ 2 prior chemotherapy regimens. 1 pt refused standard therapy. All pts were imaged with Tc-99m P2045, 8 pts received Re-188 P2045. The 7 pts who did not proceed to Re-188 P2045 were due to rapid progression (n=2) non-uptake of Tc 99m P2045 (n=2) or projected renal radiation dose above the 20 Gy limit (n=3). All pts treated with Re-188 P2045 (4 at 30 mCi/m2, 3 at 60 mCi/m2 and 1 at 90 mCi/m2) had NSCLC. The major toxicity was grade 1 or 2 lymphopenia. No dose limiting toxicities were seen. All tumors imaged by Tc-99m had uptake of Re- 188. The trial was halted at the 90 mCi/m2 level when 3 pts had projected renal radiation doses above 20Gy. No responses were seen. 5 of the 8 pts (62.5%, 95% CI: 24%, 91%) had stable disease at 8 weeks, all of whom entered with progressive disease.. Median overall survival was 11.5 mo. Conclusions: 1) Re-188 P2045 was well-tolerated. 2) Tc-99m P2045 imaging allows identification of pts who may benefit from Re-188 P2045. 3) While responses were not seen, survival for these heavily pretreated pts is encouraging. 4) Further exploration of this approach utilizing amino acid infusion to ameliorate potential renal toxicity is warranted. No significant financial relationships to disclose.