Targeted Radiopharmaceutical Therapy for Advanced Lung Cancer Phase I Trial of Rhenium Re 188 P2045, a Somatostatin Analog

Background: Both small cell and non-small cell lung cancer over-express somatostatin receptors (SSTR). P2045 peptide is an 11-amino acid somatostatin analog that binds with high affinity to SSTR and can be labeled with Tc-99m to gauge receptor prevalence or with Re-188 for 2.1 MeV 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 were required to have stage IIIb or IV or recurrent non-small cell lung cancer or extensive stage or recurrent small cell lung cancer, performance status 0 to 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 and projected renal dose of radiation froth Re-188 P2045 was less than 20 Gy, treatment with escalating doses of Re-188 P2045 was instituted. Three doses were evaluated 30 mCi/m(2), 60 mCi/m(2), and 90 mCi/m(2). A Single dose of Re-188 P2045 was allowed. Dose-limiting toxicity was defined as ? grade 3 nonhematologic toxicity or grade 4 hematologic toxicity. Results: Fifteen patients were enrolled. The median age was 61 years. Fourteen patients had >= 2 prior chemotherapy regimens. All were imaged with Tc-99m P2045, eight patients received Re-188 P2045. The most common toxicity was mild lymphopenia. The trial was halted at the 90 mCi/m(2) level when three patients were projected to have renal radiation doses above 20 Gy. The monoclonal antibody was not determined, and no responses were seen. Five of the eight patients (62.5%, 95% CI: 24-91%) had stable disease for at least 8 weeks, all of whom entered the study with progressive disease. Median overall survival was 11.5 months. Conclusions: This trial demonstrated that Re-188 P2045 was well tolerated. Tc-99m P2045 imaging allows identification of patients who may benefit from this treatment. Although responses were not seen, survival for these heavily pretreated patients is interesting and merits further research.