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1. Fatigue in patients with metastatic breast cancer undergoing single-agent taxane-based chemotherapy: a real-world data global network.

Author

Fabi, Alessandra, Gavioli, Elizabeth M., Wakade, Renuka, Spera, Maria C., Miracle, Santiago, Valveny, Neus, Butler, Elizabeth, DePizzol, Maria, Ruffini, Pier Adelchi, and Allegretti, Marcello

Abstract

Background: Cancer-related fatigue (CRF) occurs in nearly all patients with metastatic breast cancer (MBC). Objectives: This real-world analysis aimed to describe the prevalence and importance of fatigue in patients with MBC within 3 months of treatment with single-agent taxane-based chemotherapy during the timeframe of 2020–2022 in the United States and Europe. It was also conducted to assess whether there was a difference in relapsed patients compared to patients diagnosed de novo. Design: Electronic health records were analyzed from approximately 150 million patients to identify patients with MBC who underwent taxane treatment. Results: In 2021, 50,490 patients had MBC, of whom 16,170 were diagnosed de novo and 34,330 experienced relapse. The proportion of patients undergoing taxane-based chemotherapy was 7.5% (n = 1220) and 13.4% (n = 4590), respectively, and the prevalence of any fatigue and CRF was similar between the groups (24.6% versus 25.7% and 6.6% versus 5.4%, respectively). Conclusion: At least one in four patients with MBC undergoing taxane-based treatment will experience fatigue. This highlights the importance of validating screening tools to identify CRF, which is necessary to advance clinical trials aimed at investigating treatment strategies to improve patient-centered outcomes for fatigue. [ABSTRACT FROM AUTHOR]

Published
2024
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2. The therapeutic potential of an allosteric non‐competitive CXCR1/2 antagonist for diabetic nephropathy

Author

Grasselli, Chiara, primary, Bombelli, Silvia, additional, D’Esposito, Vittoria, additional, Di Tolla, Michele Francesco, additional, L’Imperio, Vincenzo, additional, Rocchio, Francesca, additional, Miscione, Martina Sara, additional, Formisano, Pietro, additional, Pagni, Fabio, additional, Novelli, Rubina, additional, Ruffini, Pier Adelchi, additional, Aramini, Andrea, additional, Allegretti, Marcello, additional, Perego, Roberto, additional, and De Filippis, Lidia, additional

Published
2023
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6. Data from Intralesional Treatment of Stage III Metastatic Melanoma Patients with L19–IL2 Results in Sustained Clinical and Systemic Immunologic Responses

Author

Weide, Benjamin, primary, Eigentler, Thomas K., primary, Pflugfelder, Annette, primary, Zelba, Henning, primary, Martens, Alexander, primary, Pawelec, Graham, primary, Giovannoni, Leonardo, primary, Ruffini, Pier Adelchi, primary, Elia, Giuliano, primary, Neri, Dario, primary, Gutzmer, Ralf, primary, Becker, Jürgen C., primary, and Garbe, Claus, primary

Published
2023
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7. Supplementary Methods from Intralesional Treatment of Stage III Metastatic Melanoma Patients with L19–IL2 Results in Sustained Clinical and Systemic Immunologic Responses

Author

Weide, Benjamin, primary, Eigentler, Thomas K., primary, Pflugfelder, Annette, primary, Zelba, Henning, primary, Martens, Alexander, primary, Pawelec, Graham, primary, Giovannoni, Leonardo, primary, Ruffini, Pier Adelchi, primary, Elia, Giuliano, primary, Neri, Dario, primary, Gutzmer, Ralf, primary, Becker, Jürgen C., primary, and Garbe, Claus, primary

Published
2023
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8. Supplementary Figure 1 from Intralesional Treatment of Stage III Metastatic Melanoma Patients with L19–IL2 Results in Sustained Clinical and Systemic Immunologic Responses

Author

Weide, Benjamin, primary, Eigentler, Thomas K., primary, Pflugfelder, Annette, primary, Zelba, Henning, primary, Martens, Alexander, primary, Pawelec, Graham, primary, Giovannoni, Leonardo, primary, Ruffini, Pier Adelchi, primary, Elia, Giuliano, primary, Neri, Dario, primary, Gutzmer, Ralf, primary, Becker, Jürgen C., primary, and Garbe, Claus, primary

Published
2023
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9. Supplementary Table 1 from Intralesional Treatment of Stage III Metastatic Melanoma Patients with L19–IL2 Results in Sustained Clinical and Systemic Immunologic Responses

Author

Weide, Benjamin, primary, Eigentler, Thomas K., primary, Pflugfelder, Annette, primary, Zelba, Henning, primary, Martens, Alexander, primary, Pawelec, Graham, primary, Giovannoni, Leonardo, primary, Ruffini, Pier Adelchi, primary, Elia, Giuliano, primary, Neri, Dario, primary, Gutzmer, Ralf, primary, Becker, Jürgen C., primary, and Garbe, Claus, primary

Published
2023
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10. Supplementary Table 2 from Intralesional Treatment of Stage III Metastatic Melanoma Patients with L19–IL2 Results in Sustained Clinical and Systemic Immunologic Responses

Author

Weide, Benjamin, primary, Eigentler, Thomas K., primary, Pflugfelder, Annette, primary, Zelba, Henning, primary, Martens, Alexander, primary, Pawelec, Graham, primary, Giovannoni, Leonardo, primary, Ruffini, Pier Adelchi, primary, Elia, Giuliano, primary, Neri, Dario, primary, Gutzmer, Ralf, primary, Becker, Jürgen C., primary, and Garbe, Claus, primary

Published
2023
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11. Supplementary Figure 2 from Intralesional Treatment of Stage III Metastatic Melanoma Patients with L19–IL2 Results in Sustained Clinical and Systemic Immunologic Responses

Author

Weide, Benjamin, primary, Eigentler, Thomas K., primary, Pflugfelder, Annette, primary, Zelba, Henning, primary, Martens, Alexander, primary, Pawelec, Graham, primary, Giovannoni, Leonardo, primary, Ruffini, Pier Adelchi, primary, Elia, Giuliano, primary, Neri, Dario, primary, Gutzmer, Ralf, primary, Becker, Jürgen C., primary, and Garbe, Claus, primary

Published
2023
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13. Abstract P5-07-09: Fatigue in patients with locally advanced or metastatic breast cancer undergoing single-agent taxane-based chemotherapy: de novo versus relapsed

Author

Blaes, Anne, primary, Gavioli, Elizabeth M., additional, Wakade, Renuka, additional, Miracle, Santiago, additional, DiTuri, Giovanna, additional, DePizzol, Maria, additional, Ruffini, Pier Adelchi, additional, Sergio, Francesco, additional, Leone, Manuela, additional, Mantelli, Flavio, additional, Allegretti, Marcello, additional, and Fabi, Alessandra, additional

Published
2023
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14. Abstract OT1-16-01: Trial In Progress: An Evaluation of FACIT-Fatigue in Patients with Locally Advanced or Metastatic Breast Cancer receiving Treatment with Taxane-based Chemotherapy

Author

Fabi, Alessandra, primary, Hager, Steven, additional, Lourdes, Laura, additional, Pedersini, Rebecca, additional, Malaguti, Paola, additional, Gavioli, Elizabeth M., additional, Wakade, Renuka, additional, Ruffini, Pier Adelchi, additional, Sergio, Francesco, additional, Leone, Manuela, additional, Mantelli, Flavio, additional, Allegretti, Marcello, additional, and Blaes, Anne, additional

Published
2023
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15. The therapeutic potential of an allosteric non-competitive CXCR1/2 antagonist for diabetic nephropathy

Author

Grasselli, C, Bombelli, S, D'Esposito, V, Di Tolla, M, L'Imperio, V, Rocchio, F, Miscione, M, Formisano, P, Pagni, F, Novelli, R, Ruffini, P, Aramini, A, Allegretti, M, Perego, R, De Filippis, L, Grasselli, Chiara, Bombelli, Silvia, D'Esposito, Vittoria, Di Tolla, Michele Francesco, L'Imperio, Vincenzo, Rocchio, Francesca, Miscione, Martina Sara, Formisano, Pietro, Pagni, Fabio, Novelli, Rubina, Ruffini, Pier Adelchi, Aramini, Andrea, Allegretti, Marcello, Perego, Roberto, De Filippis, Lidia, Grasselli, C, Bombelli, S, D'Esposito, V, Di Tolla, M, L'Imperio, V, Rocchio, F, Miscione, M, Formisano, P, Pagni, F, Novelli, R, Ruffini, P, Aramini, A, Allegretti, M, Perego, R, De Filippis, L, Grasselli, Chiara, Bombelli, Silvia, D'Esposito, Vittoria, Di Tolla, Michele Francesco, L'Imperio, Vincenzo, Rocchio, Francesca, Miscione, Martina Sara, Formisano, Pietro, Pagni, Fabio, Novelli, Rubina, Ruffini, Pier Adelchi, Aramini, Andrea, Allegretti, Marcello, Perego, Roberto, and De Filippis, Lidia

Abstract

Aims: Diabetic nephropathy is a major consequence of inflammation developing in type 1 diabetes, with interleukin-8 (IL-8)-CXCR1/2 axis playing a key role in kidney disease progression. In this study, we investigated the therapeutic potential of a CXCR1/2 non-competitive allosteric antagonist (Ladarixin) in preventing high glucose-mediated injury in human podocytes and epithelial cells differentiated from renal stem/progenitor cells (RSC) cultured as nephrospheres. Materials and Methods: We used human RSCs cultured as nephrospheres through a sphere-forming functional assay to investigate hyperglycemia-mediated effects on IL-8 signalling in human podocytes and tubular epithelial cells. Results: High glucose impairs RSC self-renewal, induces an increase in IL-8 transcript expression and protein secretion and induces DNA damage in RSC-differentiated podocytes, while exerting no effect on RSC-differentiated epithelial cells. Accordingly, the supernatant from epithelial cells or podocytes cultured in high glucose was able to differentially activate leucocyte-mediated secretion of pro-inflammatory cytokines, suggesting that the crosstalk between immune and non-immune cells may be involved in disease progression in vivo. Conclusions: Treatment with Ladarixin during RSC differentiation prevented high glucose-mediated effects on podocytes and modulated either podocyte or epithelial cell-dependent leucocyte secretion of pro-inflammatory cytokines, suggesting CXCR1/2 antagonists as possible pharmacological approaches for the treatment of diabetic nephropathy.

Published
2023

16. The therapeutic potential of an allosteric non-competitive CXCR1/2 antagonist for diabetic nephropathy

Author

Grasselli, Chiara, Bombelli, Silvia, D'Esposito, Vittoria, Di Tolla, Michele Francesco, L'Imperio, Vincenzo, Rocchio, Francesca, Miscione, Martina Sara, Formisano, Pietro, Pagni, Fabio, Novelli, Rubina, Ruffini, Pier Adelchi, Aramini, Andrea, Allegretti, Marcello, Perego, Roberto, De Filippis, Lidia, Grasselli, C, Bombelli, S, D'Esposito, V, Di Tolla, M, L'Imperio, V, Rocchio, F, Miscione, M, Formisano, P, Pagni, F, Novelli, R, Ruffini, P, Aramini, A, Allegretti, M, Perego, R, and De Filippis, L

Subjects
CXCR1/2, IL-8, type 1 diabetes, diabetic nephropathy, Ladarixin, renal stem cell
Abstract

Aims: Diabetic nephropathy is a major consequence of inflammation developing in type 1 diabetes, with interleukin-8 (IL-8)-CXCR1/2 axis playing a key role in kidney disease progression. In this study, we investigated the therapeutic potential of a CXCR1/2 non-competitive allosteric antagonist (Ladarixin) in preventing high glucose-mediated injury in human podocytes and epithelial cells differentiated from renal stem/progenitor cells (RSC) cultured as nephrospheres. Materials and methods: We used human RSCs cultured as nephrospheres through a sphere-forming functional assay to investigate hyperglycemia-mediated effects on IL-8 signalling in human podocytes and tubular epithelial cells. Results: High glucose impairs RSC self-renewal, induces an increase in IL-8 transcript expression and protein secretion and induces DNA damage in RSC-differentiated podocytes, while exerting no effect on RSC-differentiated epithelial cells. Accordingly, the supernatant from epithelial cells or podocytes cultured in high glucose was able to differentially activate leucocyte-mediated secretion of pro-inflammatory cytokines, suggesting that the crosstalk between immune and non-immune cells may be involved in disease progression in vivo. Conclusions: Treatment with Ladarixin during RSC differentiation prevented high glucose-mediated effects on podocytes and modulated either podocyte or epithelial cell-dependent leucocyte secretion of pro-inflammatory cytokines, suggesting CXCR1/2 antagonists as possible pharmacological approaches for the treatment of diabetic nephropathy.

Published
2023

17. Ladarixin, an inhibitor of IL-8 receptors CXCR1 and CXCR2, in new-onset type 1 diabetes: a multicenter, randomized, double-blind, placebo-controlled trial

Author

Piemonti, Lorenzo, Keymeulen, Bart, Gillard, Pieter, Linn, Thomas, Bosi, Emanuele, Rose, Ludger, Pozzilli, Paolo, Giorgino, Francesco, Cossu, Efisio, Daffonchio, Luisa, Goisis, Giovanni, Ruffini, Pier Adelchi, Maurizi, Anna Rita, Mantelli, Flavio, Allegretti, Marcello, Piemonti, Lorenzo, Keymeulen, Bart, Gillard, Pieter, Linn, Thoma, Bosi, Emanuele, Rose, Ludger, Pozzilli, Paolo, Giorgino, Francesco, Cossu, Efisio, Daffonchio, Luisa, Goisis, Giovanni, Ruffini, Pier Adelchi, Maurizi, Anna Rita, Mantelli, Flavio, and Allegretti, Marcello

Abstract

To evaluate the ability of ladarixin, an inhibitor of the CXCR1/2 chemokine receptors (LDX, 400 mg b.i.d for 3 cycles of 14 days on/14 days off) to maintain C-peptide production in adult patients with newly diagnosed type 1 diabetes.

Published
2022

18. Ladarixin, an inhibitor of the interleukin‐8 receptors CXCR1 and CXCR2 , in new‐onset type 1 diabetes: A multicentre, randomized, double‐blind, placebo‐controlled trial

Author

Piemonti, Lorenzo, primary, Keymeulen, Bart, additional, Gillard, Pieter, additional, Linn, Thomas, additional, Bosi, Emanuele, additional, Rose, Ludger, additional, Pozzilli, Paolo, additional, Giorgino, Francesco, additional, Cossu, Efisio, additional, Daffonchio, Luisa, additional, Goisis, Giovanni, additional, Ruffini, Pier Adelchi, additional, Maurizi, Anna Rita, additional, Mantelli, Flavio, additional, and Allegretti, Marcello, additional

Published
2022
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23. A randomized, placebo-controlled phase 2 study of paclitaxel in combination with reparixin compared to paclitaxel alone as front-line therapy for metastatic triple-negative breast cancer (fRida).

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'oncologie médicale, Goldstein, Lori J, Mansutti, Mauro, Levy, Christelle, Chang, Jenny C, Henry, Stéphanie, Fernandez-Perez, Isaura, Prausovà, Jana, Staroslawska, Elzbieta, Viale, Giuseppe, Butler, Beth, McCanna, Susan, Ruffini, Pier Adelchi, Wicha, Max S, Schott, Anne F, fRida Trial Investigators, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'oncologie médicale, Goldstein, Lori J, Mansutti, Mauro, Levy, Christelle, Chang, Jenny C, Henry, Stéphanie, Fernandez-Perez, Isaura, Prausovà, Jana, Staroslawska, Elzbieta, Viale, Giuseppe, Butler, Beth, McCanna, Susan, Ruffini, Pier Adelchi, Wicha, Max S, Schott, Anne F, and fRida Trial Investigators

Abstract

PURPOSE: CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in operable breast cancer. The fRida trial (NCT02370238) evaluated the addition of R to weekly as first-line therapy for metastatic (m) TNBC. SUBJECTS AND METHODS: Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1-21 in combination with weekly P 80 mg/m2 on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review. RESULTS: 123 subjects were randomized (62 to R + P and 61 to placebo + P). PFS was not different between the 2 groups (median 5.5 and 5.6 months for R + P and placebo + P, respectively; HR 1.13, p = 0.5996). ALDH+ and CD24-/CD44+ CSC centrally evaluated by IHC were found in 16 and 34 of the 54 subjects who provided a metastatic tissue biopsy at study entry. Serious adverse events (21.3 and 20% of subjects) and grade ≥ 3 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups. CONCLUSION: fRida is the first randomized, double-blind clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met.

Published
2021

24. CXCR1/2 inhibition enhances pancreatic islet survival after transplantation

Author

Citro, Antonio, Cantarelli, Elisa, Maffi, Paola, Nano, Rita, Melzi, Raffaella, Mercalli, Alessia, Dugnani, Erica, Sordi, Valeria, Magistretti, Paola, Daffonchio, Luisa, Ruffini, Pier Adelchi, Allegretti, Marcello, Secchi, Antonio, Bonifacio, Ezio, and Piemonti, Lorenzo

Subjects
Chemokine receptors -- Physiological aspects -- Research, Type 1 diabetes -- Research -- Patient outcomes -- Drug therapy -- Care and treatment, Allosteric proteins -- Physiological aspects -- Health aspects -- Research, Islet cell transplantation -- Health aspects -- Research, Health care industry
Abstract

Although long considered a promising treatment option for type 1 diabetes, pancreatic islet cell transformation has been hindered by immune system rejection of engrafted tissue. The identification of pathways that regulate post-transplant detrimental inflammatory events would improve management and outcome of transplanted patients. Here, we found that CXCR1/ 2 chemokine receptors and their ligands are crucial negative determinants for islet survival after transplantation. Pancreatic islets released abundant CXCR1/ 2 ligands (CXCL1 and CXCL8). Accordingly, intrahepatic CXCL1 and circulating CXCL1 and CXCL8 were strongly induced shortly after islet infusion. Genetic and pharmacological blockade of the CXCL1-CXCR1/2 axis in mice improved intrahepatic islet engraftment and reduced intrahepatic recruitment of polymorphonuclear leukocytes and NKT cells after islet infusion. In humans, the CXCR1/2 allosteric inhibitor reparixin improved outcome in a phase 2 randomized, open-label pilot study with a single infusion of allogeneic islets. These findings indicate that the CXCR1/2-mediated pathway is a regulator of islet damage and should be a target for intervention to improve the efficacy of transplantation., Introduction Achieving long-lasting insulin independence after portal vein islet transplantation has improved, but remains challenging. Nonspecific immune activation (1-6), along with preexisting and transplant-induced auto-and allospecific immune responses (7-9), are [...]

Published
2012
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25. Targeting CXCR1/2 Does Not Improve Insulin Secretion After Pancreatic Islet Transplantation : A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Type 1 Diabetes

Author

Maffi, Paola, Lundgren, Torbjorn, Tufveson, Gunnar, Rafael, Ehab, Shaw, James A. M., Liew, Aaron, Saudek, Frantisek, Witkowski, Piotr, Golab, Karolina, Bertuzzi, Federico, Gustafsson, Bengt, Daffonchio, Luisa, Ruffini, Pier Adelchi, Piemonti, Lorenzo, Nano, Rita, Mercalli, Alessia, Lampasona, Vito, Magistretti, Paola, Sordi, Valeria, Antonio, Secchi, Antonioli, Barbara, Galuzzi, Marta, Tosca, Marta Cecilia, De Carlis, Luciano, Colussi, Giacomo, Korsgren, Olle, Pollard, Helena, Maffi, Paola, Lundgren, Torbjorn, Tufveson, Gunnar, Rafael, Ehab, Shaw, James A. M., Liew, Aaron, Saudek, Frantisek, Witkowski, Piotr, Golab, Karolina, Bertuzzi, Federico, Gustafsson, Bengt, Daffonchio, Luisa, Ruffini, Pier Adelchi, Piemonti, Lorenzo, Nano, Rita, Mercalli, Alessia, Lampasona, Vito, Magistretti, Paola, Sordi, Valeria, Antonio, Secchi, Antonioli, Barbara, Galuzzi, Marta, Tosca, Marta Cecilia, De Carlis, Luciano, Colussi, Giacomo, Korsgren, Olle, and Pollard, Helena

Abstract

OBJECTIVE: Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients. RESEARCH DESIGN AND METHODS: A phase 3, multicenter, randomized, double-blind, parallel-assignment study () was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 +/- 5 after the first and day 365 +/- 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control. RESULTS: The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression. CONCLUSIONS: In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.

Published
2020
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27. CXCR1/2 pathways in paclitaxel-induced neuropathic pain

Author

Antonosante Andrea, Russo Roberto, d’Angelo Michele, Allegretti Marcello, Cimini Annamaria, Giordano Antonio, Brandolini Laura, Ruffini Pier Adelchi, Castelli Vanessa, Benedetti Elisabetta, Cristiano Loredana, Laura, Brandolini, Elisabetta, Benedetti, Adelchi, Ruffini Pier, Russo, Roberto, Loredana, Cristiano, Andrea, Antonosante, Michele, D’Angelo, Vanessa, Castelli, Antonio, Giordano, Marcello, Allegretti, and Annamaria, Cimini

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Paclitaxel, medicine.medical_treatment, Pharmacology, chemotherapy, Receptors, Interleukin-8B, Chemotherapy, Chronic pain, CXCR1/2 inhibitor, IL-8, Microtubules, Oncology, Receptors, Interleukin-8A, microtubules, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Rats, Wistar, Taxane, business.industry, Interleukin-8, Neurotoxicity, medicine.disease, Antineoplastic Agents, Phytogenic, Rats, Surgery, 030104 developmental biology, Allodynia, Peripheral neuropathy, chemistry, Neuropathic pain, Neuralgia, medicine.symptom, chronic pain, business, 030217 neurology & neurosurgery, Research Paper
Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain that represents a frequent and serious consequence of chemotherapy agents. Over the last years, significant progress has been achieved in elucidating the underlying pathogenesis of CIPN. The interference of taxanes with microtubule has been proposed as a mechanism that leads to altered axonal transport and to permanent neurological damages. The inflammatory process activated by chemotherapeutic agents has been considered as a potential trigger of nociceptive process in CIPN. In this study we investigated the effect of reparixin, an inhibitor of CXCR1/CXCR2, in suppressing the development of paclitaxel-induced nociception in rats. Moreover, reparixin activity in reversing the neurotoxic effects induced by paclitaxel or GRO/KC in F11 cells was also analyzed. Reparixin administered by continuous infusion ameliorated paclitaxel-induced mechanical and cold allodynia in rats. In F11 cells, reparixin was able to inhibit the increase of acetyladed α-tubulin induced both by paclitaxel and GRO/KC. The subsequent experiments were performed in order to dissect the signal transduction pathways under GRO/KC control, eventually modulated by paclitaxel and/or reparixin. To this aim we found that reparixin significantly counteracted p-FAK, p-JAK2/p-STAT3, and PI3K-p-cortactin activation induced either by paclitaxel or GRO/KC. Overall the present results have identified IL-8/CXCR1/2 pathway as a mechanism involved in paclitaxel-induced peripheral neuropathy. In particular, the obtained data suggest that the inhibition of CXCR1/2 combined with standard taxane therapy, in addition to potentiating the taxane anti-tumor activity can reduce chemotherapy-induced neurotoxicity, thus giving some insight for the development of novel treatments.

Published
2017

28. A randomized, placebo-controlled phase 2 study of paclitaxel in combination with reparixin compared to paclitaxel alone as front-line therapy for metastatic triple-negative breast cancer (fRida).

Author

Goldstein, Lori J., Mansutti, Mauro, Levy, Christelle, Chang, Jenny C., Henry, Stephanie, Fernandez-Perez, Isaura, Prausovà, Jana, Staroslawska, Elzbieta, Viale, Giuseppe, Butler, Beth, McCanna, Susan, Ruffini, Pier Adelchi, Wicha, Max S., Schott, Anne F., for the fRida Trial Investigators, Alvarez, Ricardo H., Abu-Khalaf, Maysa, Ibrahim, Nuhad, Daniel, Brooke, and Meshad, Michael

Abstract

Purpose: CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in operable breast cancer. The fRida trial (NCT02370238) evaluated the addition of R to weekly as first-line therapy for metastatic (m) TNBC. Subjects and Methods: Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1–21 in combination with weekly P 80 mg/m2 on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review. Results: 123 subjects were randomized (62 to R + P and 61 to placebo + P). PFS was not different between the 2 groups (median 5.5 and 5.6 months for R + P and placebo + P, respectively; HR 1.13, p = 0.5996). ALDH+ and CD24−/CD44+ CSC centrally evaluated by IHC were found in 16 and 34 of the 54 subjects who provided a metastatic tissue biopsy at study entry. Serious adverse events (21.3 and 20% of subjects) and grade ≥ 3 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups. Conclusion: fRida is the first randomized, double-blind clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met. Clinical Trial Registration/Date of Registration: NCT01861054/February 24, 2015. [ABSTRACT FROM AUTHOR]

Published
2021
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35. Abstract CT057: A single-arm, preoperative, pilot study to evaluate the safety and biological effects of orally administered reparixin in early breast cancer patients who are candidates for surgery

Author

Goldstein, Lori J., primary, Perez, Raymond P., additional, Yardley, Denise A., additional, Han, Linda K., additional, Reuben, James M., additional, McCanna, Susan, additional, Butler, Beth, additional, Ruffini, Pier Adelchi, additional, and Chang, Jenny C., additional

Published
2016
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36. Abstract C22: A phase Ib study of the CXCR1/2 inhibitor Reparixin in combination with weekly paclitaxel in metastatic HER2 negative breast cancer - final analysis

Author

Schott, Anne F., primary, Wicha, Max S., additional, Perez, Raymond P., additional, Kato, Giraldo, additional, Avery, Tiffany, additional, Cristofanilli, Massimo, additional, Reuben, James M., additional, Alpaugh, R. Katherine, additional, Ruffini, Pier Adelchi, additional, Mccanna, Susan, additional, and Goldstein, Lori J., additional

Published
2015
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37. Targeting CXCR1 on breast cancer stem cells: signaling pathways and clinical application modelling

Author

Brandolini, Laura, primary, Cristiano, Loredana, additional, Fidoamore, Alessia, additional, De Pizzol, Maria, additional, Di Giacomo, Erica, additional, Florio, Tiziana Marilena, additional, Confalone, Giuseppina, additional, Galante, Angelo, additional, Cinque, Benedetta, additional, Benedetti, Elisabetta, additional, Ruffini, Pier Adelchi, additional, Cifone, Maria Grazia, additional, Giordano, Antonio, additional, Alecci, Marcello, additional, Allegretti, Marcello, additional, and Cimini, Annamaria, additional

Published
2015
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39. Abstract P6-03-01: A phase Ib study of the CXCR1/2 inhibitor reparixin in combination with weekly paclitaxel in metastatic HER2 negative breast cancer – First analysis

Author

Schott, Anne F, primary, Wicha, Max S, additional, Perez, Raymond P, additional, Kato, Giraldo, additional, Avery, Tiffany, additional, Cristofanilli, Massimo, additional, Reuben, James M, additional, Alpaugh, R Katherine, additional, McCanna, Susan, additional, Ruffini, Pier Adelchi, additional, and Goldstein, Lori J, additional

Published
2015
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41. Idiotype-specific immunotherapy in multiple myeloma: suggestions for future directions of research

Author

Bogen, Bjame, Ruffini, Pier Adelchi, Alexandre Corthay, Fredriksen, Agnete B., Froyland, Marianne, Lundin, Katrin, Rosjo, Egil, Thompson, Keith, and Massaia, Massimo

Subjects
Immunoglobulin Idiotypes, Antigens, Neoplasm, Humans, Immunotherapy, Multiple Myeloma
Abstract

Multiple myeloma (MM) remains a difficult-to-cure cancer and less than 20% of patients achieve long-term survival irrespective of the treatment delivered, including high-dose chemotherapy. Thus, new treatment modalities are urgently needed. Myeloma cells produce a monoclonal immunoglobulin (Ig) which is a truly tumor-specific antigen. The tumor-specific antigenic determinants are localized in the variable regions of the monoclonal Ig and are termed idiotopes (Id). Id-vaccination, i.e., vaccination with the autologous monoclonal Ig, has been performed in MM patients in order to elicit tumor-specific immune responses and possibly elimination of myeloma cells. However, clinical trials have not given the promising results obtained in mice. This review focuses on tolerance mechanisms that might hinder Id-specific immune responses in MM patients. New strategies for Id vaccination in MM are discussed.

Published
2006

43. CXCR1/2 Inhibition Blocks and Reverses Type 1 Diabetes in Mice

Author

Citro, Antonio, primary, Valle, Andrea, additional, Cantarelli, Elisa, additional, Mercalli, Alessia, additional, Pellegrini, Silvia, additional, Liberati, Daniela, additional, Daffonchio, Luisa, additional, Kastsiuchenka, Olga, additional, Ruffini, Pier Adelchi, additional, Battaglia, Manuela, additional, Allegretti, Marcello, additional, and Piemonti, Lorenzo, additional

Published
2014
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44. Intralesional Treatment of Stage III Metastatic Melanoma Patients with L19–IL2 Results in Sustained Clinical and Systemic Immunologic Responses

Author

Weide, Benjamin, primary, Eigentler, Thomas K., additional, Pflugfelder, Annette, additional, Zelba, Henning, additional, Martens, Alexander, additional, Pawelec, Graham, additional, Giovannoni, Leonardo, additional, Ruffini, Pier Adelchi, additional, Elia, Giuliano, additional, Neri, Dario, additional, Gutzmer, Ralf, additional, Becker, Jürgen C., additional, and Garbe, Claus, additional

Published
2014
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45. Intralesional treatment of stage III metastatic melanoma patients with L19-IL2: Clinical and systemic immunological responses.

Author

Neri, Dario, primary, Weide, Benjamin, additional, Eigentler, Thomas K., additional, Pflugfelder, Annette, additional, Zelba, Henning, additional, Pawelec, Graham P., additional, Giovannoni, Leonardo, additional, Ruffini, Pier Adelchi, additional, Elia, Giuliano, additional, Gutzmer, Ralf, additional, Becker, Jürgen C., additional, and Garbe, Claus, additional

Published
2014
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46. A phase II study of intratumoral application of L19IL2/L19TNF in melanoma patients in clinical stage III or stage IV M1a with presence of injectable cutaneous and/or subcutaneous lesions.

Author

Danielli, Riccardo, primary, Patuzzo, Roberto, additional, Di Giacomo, Anna Maria, additional, Gallino, Gianfranco, additional, Di Florio, Annabella, additional, Cutaia, Ornella, additional, Lazzeri, Andrea, additional, Fazio, Carolina, additional, Giovannoni, Leonardo, additional, Ruffini, Pier Adelchi, additional, Elia, Giuliano, additional, Neri, Dario, additional, Santinami, Mario, additional, and Maio, Michele, additional

Published
2014
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50. Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer

Author

Santini, Daniele, primary, Vincenzi, Bruno, additional, Fratto, Maria Elisabetta, additional, Perrone, Giuseppe, additional, Lai, Raymond, additional, Catalano, Vincenzo, additional, Cass, Carol, additional, Ruffini, Pier Adelchi, additional, Spoto, Chiara, additional, Muretto, Pietro, additional, Rizzo, Sergio, additional, Muda, Andrea Onetti, additional, Mackey, John R., additional, Russo, Antonio, additional, Tonini, Giuseppe, additional, and Graziano, Francesco, additional

Published
2010
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