¹⁷⁷Lu-PSMA for Extended Treatment of Metastatic Castration-Resistant Prostate Cancer

Prostate-Specific Membrane Antigen: Gateway to Management of Advanced Prostate Cancer

“…The number of cycles, amount of injected activity, and time intervals between cycles were derived empirically, and further trials may be required for additional optimization. First studies demonstrated that a rechallenge RLT after this number of cycles showed acceptable safety profiles and higher response rates than other systemic therapies and provided a rationale to pursue this salvage RLT approach further (87,88).…”

Investigation of image-based lesion and kidney dosimetry protocols for 177Lu-PSMA-I&T therapy with and without a late SPECT/CT acquisition

“…Therefore, in March 2022, the FDA approved the first radioactive compound targeting mCRPC, namely Pluvicto ™ (Novartis AG), formerly known as 177 Lu-PSMA-617 [5]. Furthermore, a clinical study has been started in February 2022 investigating the compound 177 Lu-PSMA-I&T for mCRPC [6]. Recently, the European Association of Nuclear Medicine has published guidelines covering internal dosimetry of 177 Lu-labeled PSMA ligands with regard to skin, bone marrow and blood, glands, kidneys and tumors [7].…”

How Can Radiopharmaceutical Therapies Reach Their Full Potential? Improving Dose Reporting and Phase I Clinical Trial Design

“…6,13 On the basis of published RPT data showing that patients who received extended treatment courses exceeding these normal organ dose constraints still have limited toxicity, there is a specific concern in the field that the majority of patients treated with RPTs are undertreated. 4,[14][15][16][17][18][19][20][21][22] The inability to escalate beyond the above constraints in clinical trials leads to many phase I RPT trials stopping escalation before any DLT is observed, as opposed to other phase I trials with escalation guided primarily by clinical toxicity (Fig 1). This precludes treatment optimization with many RPT agents.…”

“…2,3,5,28,29 In addition, for 177 Lu-PSMA therapy, studies suggest a higher threshold also may be safe, especially for patients without renal risk factors, but Steinhelfer et al 32 confirm the importance of long-term follow-up for renal toxicity (see Data Supplement discussion). 14,15,22,[30][31][32][33] For patients in phase I trials and those in last line treatment options, the benefits of enhanced treatment efficacy may outweigh the risk of late renal toxicity because of short life expectancy.…”

“…In terms of the overall controversy noted above regarding AD constraints for bone marrow (2 Gy) and kidney (23 Gy), there is already evidence that these limits can often be safely exceeded in clinical practice in patients receiving multiple courses or extended cycles of RPT. 4,14,15,22 This suggests that current treatment regimens also merit reevaluation to assess whether larger initial administered activities per cycle are tolerable. In particular, in the bone marrow, acute toxicity is readily observable during the phase I DLT observation period (typically 3-8 weeks after administration).…”