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Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer

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Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer. / Amsberg, Gunhild von; Zilles, Mirjam; Mansour, Wael; Gild, Philipp; Alsdorf, Winfried; Kaune, Moritz; Böckelmann, Lukas Clemens; Hauschild, Jessica; Krisp, Christoph; Rohlfing, Tina; Saygi, Ceren; Alawi, Malik; Zielinski, Alexandra; Langebrake, Claudia; Su, Xiong; Perner, Sven; Tilki, Derya; Schluter, Hartmut; Graefen, Markus; Dyshlovoy, Sergey; Bokemeyer, Carsten.

In: INT J MOL SCI, Vol. 23, No. 23, 14948, 29.11.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Amsberg, GV, Zilles, M, Mansour, W, Gild, P, Alsdorf, W, Kaune, M, Böckelmann, LC, Hauschild, J, Krisp, C, Rohlfing, T, Saygi, C, Alawi, M, Zielinski, A, Langebrake, C, Su, X, Perner, S, Tilki, D, Schluter, H, Graefen, M, Dyshlovoy, S & Bokemeyer, C 2022, 'Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer', INT J MOL SCI, vol. 23, no. 23, 14948. https://doi.org/10.3390/ijms232314948

APA

Amsberg, G. V., Zilles, M., Mansour, W., Gild, P., Alsdorf, W., Kaune, M., Böckelmann, L. C., Hauschild, J., Krisp, C., Rohlfing, T., Saygi, C., Alawi, M., Zielinski, A., Langebrake, C., Su, X., Perner, S., Tilki, D., Schluter, H., Graefen, M., ... Bokemeyer, C. (2022). Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer. INT J MOL SCI, 23(23), [14948]. https://doi.org/10.3390/ijms232314948

Vancouver

Amsberg GV, Zilles M, Mansour W, Gild P, Alsdorf W, Kaune M et al. Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer. INT J MOL SCI. 2022 Nov 29;23(23). 14948. https://doi.org/10.3390/ijms232314948

Bibtex

@article{24a51ec35cf24d0f9b720bb0327a81e7,
title = "Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer",
abstract = "Significant progress has been achieved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, results in patients with aggressive variant prostate cancer (AVPC) have been disappointing. Here, we report retrospectively collected data from intensively pretreated AVPC patients (n = 17; 88.2% visceral metastases; 82% elevation of neuroendocrine markers) treated with salvage chemotherapy consisting of cisplatin, ifosfamide, and paclitaxel (TIP). At the interim analysis, 60% of patients showed radiographic response or stable disease (PFS = 2.5 months; OS = 6 months). In men who responded to chemotherapy, an OS > 15 months was observed. Preclinical analyses confirmed the high activity of the TIP regimen, especially in docetaxel-resistant prostate cancer cells. This effect was primarily mediated by increased cisplatin sensitivity in the emergence of taxane resistance. Proteomic and functional analyses identified a lower DNA repair capacity and cell cycle machinery deficiency to be causative. In contrast, paclitaxel showed inconsistent effects, partially antagonizing cisplatin and ifosfamide in some AVPC models. Consequently, paclitaxel has been excluded from the TIP combination for future patients. In summary, we report for the first time the promising efficacy of TIP as salvage therapy in AVPC. Our preclinical data indicate a pivotal role for cisplatin in overcoming docetaxel resistance.",
keywords = "Male, Humans, Paclitaxel/therapeutic use, Prostatic Neoplasms, Castration-Resistant/drug therapy, Retrospective Studies, Proteomics, Cisplatin/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Salvage Therapy/methods, Docetaxel/therapeutic use, Treatment Outcome",
author = "Amsberg, {Gunhild von} and Mirjam Zilles and Wael Mansour and Philipp Gild and Winfried Alsdorf and Moritz Kaune and B{\"o}ckelmann, {Lukas Clemens} and Jessica Hauschild and Christoph Krisp and Tina Rohlfing and Ceren Saygi and Malik Alawi and Alexandra Zielinski and Claudia Langebrake and Xiong Su and Sven Perner and Derya Tilki and Hartmut Schluter and Markus Graefen and Sergey Dyshlovoy and Carsten Bokemeyer",
year = "2022",
month = nov,
day = "29",
doi = "10.3390/ijms232314948",
language = "English",
volume = "23",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "23",

}

RIS

TY - JOUR

T1 - Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer

AU - Amsberg, Gunhild von

AU - Zilles, Mirjam

AU - Mansour, Wael

AU - Gild, Philipp

AU - Alsdorf, Winfried

AU - Kaune, Moritz

AU - Böckelmann, Lukas Clemens

AU - Hauschild, Jessica

AU - Krisp, Christoph

AU - Rohlfing, Tina

AU - Saygi, Ceren

AU - Alawi, Malik

AU - Zielinski, Alexandra

AU - Langebrake, Claudia

AU - Su, Xiong

AU - Perner, Sven

AU - Tilki, Derya

AU - Schluter, Hartmut

AU - Graefen, Markus

AU - Dyshlovoy, Sergey

AU - Bokemeyer, Carsten

PY - 2022/11/29

Y1 - 2022/11/29

N2 - Significant progress has been achieved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, results in patients with aggressive variant prostate cancer (AVPC) have been disappointing. Here, we report retrospectively collected data from intensively pretreated AVPC patients (n = 17; 88.2% visceral metastases; 82% elevation of neuroendocrine markers) treated with salvage chemotherapy consisting of cisplatin, ifosfamide, and paclitaxel (TIP). At the interim analysis, 60% of patients showed radiographic response or stable disease (PFS = 2.5 months; OS = 6 months). In men who responded to chemotherapy, an OS > 15 months was observed. Preclinical analyses confirmed the high activity of the TIP regimen, especially in docetaxel-resistant prostate cancer cells. This effect was primarily mediated by increased cisplatin sensitivity in the emergence of taxane resistance. Proteomic and functional analyses identified a lower DNA repair capacity and cell cycle machinery deficiency to be causative. In contrast, paclitaxel showed inconsistent effects, partially antagonizing cisplatin and ifosfamide in some AVPC models. Consequently, paclitaxel has been excluded from the TIP combination for future patients. In summary, we report for the first time the promising efficacy of TIP as salvage therapy in AVPC. Our preclinical data indicate a pivotal role for cisplatin in overcoming docetaxel resistance.

AB - Significant progress has been achieved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, results in patients with aggressive variant prostate cancer (AVPC) have been disappointing. Here, we report retrospectively collected data from intensively pretreated AVPC patients (n = 17; 88.2% visceral metastases; 82% elevation of neuroendocrine markers) treated with salvage chemotherapy consisting of cisplatin, ifosfamide, and paclitaxel (TIP). At the interim analysis, 60% of patients showed radiographic response or stable disease (PFS = 2.5 months; OS = 6 months). In men who responded to chemotherapy, an OS > 15 months was observed. Preclinical analyses confirmed the high activity of the TIP regimen, especially in docetaxel-resistant prostate cancer cells. This effect was primarily mediated by increased cisplatin sensitivity in the emergence of taxane resistance. Proteomic and functional analyses identified a lower DNA repair capacity and cell cycle machinery deficiency to be causative. In contrast, paclitaxel showed inconsistent effects, partially antagonizing cisplatin and ifosfamide in some AVPC models. Consequently, paclitaxel has been excluded from the TIP combination for future patients. In summary, we report for the first time the promising efficacy of TIP as salvage therapy in AVPC. Our preclinical data indicate a pivotal role for cisplatin in overcoming docetaxel resistance.

KW - Male

KW - Humans

KW - Paclitaxel/therapeutic use

KW - Prostatic Neoplasms, Castration-Resistant/drug therapy

KW - Retrospective Studies

KW - Proteomics

KW - Cisplatin/therapeutic use

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Salvage Therapy/methods

KW - Docetaxel/therapeutic use

KW - Treatment Outcome

U2 - 10.3390/ijms232314948

DO - 10.3390/ijms232314948

M3 - SCORING: Journal article

C2 - 36499277

VL - 23

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 23

M1 - 14948

ER -