Clinical evaluation of efficacy and safety of ¹⁷⁷Lu-EDTMP in patients with Painful Skeletal Metastasis: a multiparametric comparison with ¹⁵³Sm-EDTMP on equidose basis

Abstract

The purpose of the study was to assess the efficacy and safety profile of ¹⁷⁷Lu-EDTMP in patients with painful skeletal metastasis and make a comparative evaluation of the efficacy with that of ¹⁵³Sm-EDTMP. Methods: A total of 32 patients with painful skeletal metastases were prospectively evaluated (26 men and 6 women; mean age of 46.19 years; age range: 33-84 years). Patients were divided in two groups, Patients treated with ¹⁷⁷Lu-EDTMP (n = 16) and those treated with ¹⁵³Sm-EDTMP (n = 16). In both the groups, patients were treated with dose of 37MBq/kg body weight for both the radionuclide (dose range of ¹⁷⁷Lu-EDTMP varied from 1295 MBq to 2701 MBq depending on the weight of patient, whereas in ¹⁵³Sm-EDTMP the dose range varied from 1258 MBq to 2553 MBq). The following evaluation scores were adopted to examine the efficacy: [i] Analgesic score, [ii] pain scale (visual analogue scale or VAS), [iii] quality of life evaluation using 3 assessment scales (EORTC, Karnofsky and ECOG assessment scales), [iv] bone proliferation marker (estimation of bone alkaline phosphatase or BAP). The hematological toxicity was evaluated using NCI-Common Terminology Criteria for Adverse Events (CTCAE) and was compared between both groups at baseline and each monthly till 3 months post therapy. For the assessment of pain response post-therapy, a pre-defined criteria was followed used in this study protocol that considered both the VAS and analgesic score change on a sliding scale (rather than a single parameter or an absolute value), and the response was subdivided into 4 categories: complete response (CR), partial response (PR), minimal response (MR) and no-response (NR). Results: The overall pain relief in patients treated with ¹⁷⁷Lu-EDTMP was 80%. Among the responders, 50% of patients had complete response (CR), 41.67 % had partial response (PR) and 8.33% had minimal response (MR). The overall pain relief in patients treated with ¹⁵³Sm-EDTMP was 75%. Among these, 33.33% of patients had complete response (CR), 58.33% had partial response (PR) and 8.33% had minimal response (MR). The difference in pain relief between these two groups was not significant (P = 1.000). There was significant improvement in quality of life post therapy at 3 month in both group of patients as assessed by ECOG (P =0.014 and 0.005) and Karnofsky indices (P =0.007 and 0.023) respectively for ¹⁷⁷Lu-EDTMP and ¹⁵³Sm-EDTMP. There was significant improvement in quality of life (pain free survival) post therapy at 3 month in both group of patients as assessed by EORTC QLQ BM22 score (P = 0.004 and <0.001) respectively for ¹⁷⁷Lu-EDTMP and ¹⁵³Sm-EDTMP. Bone proliferation marker in responders showed significant reduction in both groups [¹⁷⁷Lu-EDTMP (P =0.008) and ¹⁵³Sm-EDTMP (P =0.019)], parallel to the clinical response. In patients treated with ¹⁷⁷Lu-EDTMP non-serious (Grade I / II) anemia, leucopenia and thrombocytopenia was noted in 46.67%, 46.67% and 20% respectively. In patients treated with ¹⁷⁷Lu-EDTMP serious (Grade III / IV) anemia, leucopenia and thrombocytopenia was noted in 20%, 6.67% and 0% respectively. In patients treated with ¹⁵³Sm-EDTMP non-serious (Grade I / II) anemia, leucopenia and thrombocytopenia was noted in 62.5%, 31.25% and 18.75% respectively. In patients treated with ¹⁵³Sm-EDTMP serious (Grade III / IV) anemia, leucopenia and thrombocytopenia was noted in 18.75%, 0% and 6.25% respectively. Only 1 patient treated with ¹⁵³Sm-EDTMP showed Grade IV thrombocytopenia, however no blood transfusion was required. No statistically significant difference noted in non-serious toxicity between two groups with respect to anemia (P = 0.571), leucopenia (P = 0.511) and thrombocytopenia (P = 0.561). No statistically significant difference noted in serious toxicity between two groups with respect to anemia (P = 0.671), leucopenia (P = 0.334) and thrombocytopenia (P = 0.739). 3 out of 12 responders (25% of the responders) treated with ¹⁷⁷Lu-EDTMP reported incidence of flare phenomenon, on 3rd day post therapy and 1 (8.33%) reported on 5th day post therapy, showing no response to therapy. In ¹⁵³Sm-EDTMP group, 2 out of 12 responders (16.66% of the responders) reported incidence of flare phenomenon, reported on 3rd day post therapy. Conclusion: The present study documented a similar pain response efficacy of ¹⁷⁷Lu-EDTMP coupled with improvement in the quality of life when compared to that of ¹⁵³Sm-EDTMP. Similar hematological toxicity profile and absence of renal toxicity demonstrated with ¹⁷⁷Lu-EDTMP would indicate that this agent is a feasible and safe alternative to ¹⁵³Sm-EDTMP for treatment of painful skeletal metastasis with minimal side effects especially in the setting of centers having no nearby accessibility for ¹⁵³Sm-EDTMP because of its longer half life. This is an important consideration taking into account that ¹⁷⁷Lu is a popular radionuclide for PRRT in many centres across the world.