Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study

Autenrieth, Michael; Seidl, Christof; Bruchertseifer, Frank; Horn, Thomas; Kurtz, F.; Feuerecker, Benedikt; D’Alessandria, Calogero; Pfob, Christian H.; Nekolla, Stephan G.; Apostolidis, Christos; Mirzadeh, Saed; Gschwend, Jürgen E.; Schwaiger, Markus; Scheidhauer, Klemens; Morgenstern, Alfred

doi:10.1007/s00259-018-4003-6

Cited by 57 publications

(40 citation statements)

References 33 publications

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“…This could be due to preponderance of Ta (77.43 %, 10/14) in recurring group. Though originally cloned from a bladder cancer cell line [18], DSC3 expression has not been evaluated in bladder cancer. In this study, we found DSC3 expression in 68.8%.…”

Section: Discussionmentioning

confidence: 99%

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A Clinical Trial of the Intradermal TLR2 Agonist CADI-05 for BCG Recurrent and Unresponsive Non-Muscle Invasive Bladder Cancer

O’Donnell

Singh

Sood

et al. 2019

BLC

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Background: CADI-05, a TLR-2 agonist, induces Th1 immune response following intradermal administration and has been found useful in management of lung cancer and melanoma. Objective: To evaluate CADI-05 in patients with BCG recurrent and unresponsive Non-muscle invasive bladder cancer (NMIBC) for 15-months recurrence free survival (RFS) rate. Methods: In BCG unresponsive (BU) or recurrent (BR) NMIBC, CADI-05 was administered intradermally every two weeks for 3 months followed by every month for 3 months and subsequently every 2 months for 6 months following transurethral resection (TUR) in a single arm study (ClinicalTrials.gov: NCT00694798). Cystoscopy, cytology, and sonography were performed for the presence/recurrence of NMIBC at 3, 6, 9, 12, 15 months and beyond and confirmed by biopsy. Evaluation of preoperative biopsy for Desmocollin-3 (DSC3) expression and tumor infiltrating lymphocytes (TIL) was optional. -Commercial License (CC BY-NC 4.0). 172 M. Results: Twenty patients with NMIBC received intradermal CADI-05. RFS at 15 and 30 months was 35% (7/20) patients. The median RFS was also better for BU compared to BR group (HR, 0.329; 95% CI, 0.071 to 1.532). DSC3 expression was present in 68.8% (11/16) patients. TIL and RFS beyond 30 months were seen 2.3 times and 2.8 times more often in DSC3 expressing NMIBC respectively. No grade IV or V adverse events occurred. Local site reactions were the most common adverse event. Conclusion: Intradermal CADI-05 following TUR is associated with 35% RFS at 30 months.

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Section: Discussionmentioning

confidence: 99%

“…It achieves complete response (CR) in 21 % only, and the durability of CR is 4% at two years [17]. Thus, there is a need for better treatment options and this is an active area of research [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

A Clinical Trial of the Intradermal TLR2 Agonist CADI-05 for BCG Recurrent and Unresponsive Non-Muscle Invasive Bladder Cancer

O’Donnell

Singh

Sood

et al. 2019

BLC

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“…Because of its convenient mode of distribution in the form of a generator, 213 Bi was the first of the two radionuclides to be tested in patients. To date, it has been used to treat more than 200 patients in combination with radioligands targeted to leukemia, lymphoma, melanoma, bladder cancer, glioma, and neuroendocrine tumors . The summary of clinical experience with 213 Bi is shown in Table .…”

Section: Clinical Experience With 213bi and 225acmentioning

confidence: 99%

Targeted alpha therapy with bismuth‐213 and actinium‐225: Meeting future demand

Bruchertseifer

Kellerbauer

Malmbeck

et al. 2019

Labelled Comp Radiopharmac

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Targeted alpha therapy (TAT) is a promising approach for the treatment of cancer. The use of alpha emitters for cancer therapy has two distinct advantages over conventional therapies. The short range of alpha radiation in human tissue (less than 0.1 mm), corresponding to only a few cell diameters, allows selective killing of targeted cancer cells while sparing surrounding healthy tissue. At the same time, the high energy (several MeV) of alpha radiation and its associated high linear energy transfer leads to highly effective cell kill. Consequently, alpha radiation can destroy cells which otherwise exhibit resistance to treatment with beta or gamma irradiation or chemotherapeutic drugs, and can thus offer a therapeutic option for tumors resistant to conventional therapies. Recent results demonstrating the remarkable therapeutic efficacy of alpha emitters to treat various cancers have underlined the clinical potential of TAT. This paper describes the recent clinical experience with 213Bi and 225Ac. In view of the enormous benefit of targeted cancer treatment with alpha emitters, their production will have to be considerably increased beyond current supply capabilities. Alternative production methods based on the irradiation of uranium, thorium, or radium targets at reactors or accelerator facilities have the potential to meet future demand.

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“…A follow-up study investigating a fractionation regime underlined the safety and efficacy of the concept [15]. Based on the promising preclinical results, a pilot study in 12 patients resistant to standard therapy and scheduled for cystectomy was conducted [1]. Patients were offered salvage treatment by intravesical instillation of 213 Bilabelled anti-EGFR monoclonal antibody.…”

Section: Radioimmunotherapy Of Bladder Cancer With 213 Bimentioning

confidence: 99%

“…In recent years, several promising compounds labelled with 225 Actinium or 213 Bismuth have been developed for targeted alpha therapy of bladder cancer [1], neuroendocrine [2,3] and brain tumours [4][5][6][7], as well as prostate cancer [8][9][10][11][12][13]. Although the remarkable therapeutic results obtained with 225 Ac-PSMA-617 for therapy of advanced prostate cancer have mainly stimulated the recent rise in global interest in targeted alpha therapy, other compounds such as 213 Bi-/ 225 Ac-Substance P for therapy of brain tumours, 213 Bi-/ 225 Ac-DO-TATOC for therapy of neuroendocrine tumours, or 213 Bilabelled anti-EGFR antibodies for locoregional treatment of bladder cancer also have shown great promise and deserve further study.…”

Section: Introductionmentioning

confidence: 99%

Development of Targeted Alpha Therapy from Bench to Bedside

Morgenstern

Bruchertseifer

2019

Journal of Medical Imaging and Radiation Sciences

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Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study

Abstract: Intravesical instillation of Bi-anti-EGFR monoclonal antibody was well tolerated and showed therapeutic efficacy. Repeated instillation and/or instillation of higher activities of theBi-immunoconjugate might lead to better therapeutic outcomes. A phase I clinical trial is planned.

Cited by 57 publications

References 33 publications

A Clinical Trial of the Intradermal TLR2 Agonist CADI-05 for BCG Recurrent and Unresponsive Non-Muscle Invasive Bladder Cancer

A Clinical Trial of the Intradermal TLR2 Agonist CADI-05 for BCG Recurrent and Unresponsive Non-Muscle Invasive Bladder Cancer

Targeted alpha therapy with bismuth‐213 and actinium‐225: Meeting future demand

Development of Targeted Alpha Therapy from Bench to Bedside

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