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A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis
SIMPLE SUMMARY: This study is one of the very few phase I trials on intraperitoneal chemotherapy applied as PIPAC. Cisplatin and doxorubicin may be safely used as PIPAC at a dose of 30 mg/m(2) and 6 mg/m(2), respectively; oxaliplatin can be used at an intraperitoneal dose of 135 mg/m(2). No serious...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958944/ https://www.ncbi.nlm.nih.gov/pubmed/33802269 http://dx.doi.org/10.3390/cancers13051060 |
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author | Robella, Manuela De Simone, Michele Berchialla, Paola Argenziano, Monica Borsano, Alice Ansari, Shoeb Abollino, Ornella Ficiarà, Eleonora Cinquegrana, Armando Cavalli, Roberta Vaira, Marco |
author_facet | Robella, Manuela De Simone, Michele Berchialla, Paola Argenziano, Monica Borsano, Alice Ansari, Shoeb Abollino, Ornella Ficiarà, Eleonora Cinquegrana, Armando Cavalli, Roberta Vaira, Marco |
author_sort | Robella, Manuela |
collection | PubMed |
description | SIMPLE SUMMARY: This study is one of the very few phase I trials on intraperitoneal chemotherapy applied as PIPAC. Cisplatin and doxorubicin may be safely used as PIPAC at a dose of 30 mg/m(2) and 6 mg/m(2), respectively; oxaliplatin can be used at an intraperitoneal dose of 135 mg/m(2). No serious adverse event was reported. The dosages achieved to date are the highest ever used in PIPAC. The results of these investigations should be the starting point for further clinical phase II trials regarding repeated PIPAC, possibly associated with systemic chemotherapy. ABSTRACT: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an innovative laparoscopic intraperitoneal chemotherapy approach with the advantage of a deeper tissue penetration. Thus far, oxaliplatin has been administered at an arbitrary dose of 92 mg/m(2), cisplatin at 7.5 mg/m(2) and doxorubicin 1.5 mg/m(2). This is a model-based approach phase I dose escalation study with the aim of identifying the maximum tolerable dose of the three different drugs. The starting dose of oxaliplatin was 100 mg/m(2); cisplatin was used in association with doxorubicin: 15 mg/m(2) and 3 mg/m(2) were the respective starting doses. Safety was assessed according to Common Terminology Criteria for Adverse Events (CTCAE version 4.03). Thirteen patients were submitted to one PIPAC procedure. Seven patients were treated with cisplatin and doxorubicin and 6 patients with oxaliplatin; no dose limiting toxicities and major side effects were found. Common adverse events included postoperative abdominal pain and nausea. The maximum tolerable dose was not reached. The highest dose treated cohort (oxaliplatin 135 mg/m(2); cisplatin 30 mg/m(2) and doxorubicin 6 mg/m(2)) tolerated PIPAC well. Serological analyses revealed no trace of doxorubicin at any dose level. Serum levels of cis- and oxaliplatin reached a peak at 60–120 min after PIPAC and were still measurable in the circulation 24 h after the procedure. Cisplatin and doxorubicin may be safely used as PIPAC at a dose of 30 mg/m(2) and 6 mg/m(2), respectively; oxaliplatin can be used at an intraperitoneal dose of 135 mg/m(2). The dosages achieved to date are the highest ever used in PIPAC. |
format | Online Article Text |
id | pubmed-7958944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79589442021-03-16 A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis Robella, Manuela De Simone, Michele Berchialla, Paola Argenziano, Monica Borsano, Alice Ansari, Shoeb Abollino, Ornella Ficiarà, Eleonora Cinquegrana, Armando Cavalli, Roberta Vaira, Marco Cancers (Basel) Article SIMPLE SUMMARY: This study is one of the very few phase I trials on intraperitoneal chemotherapy applied as PIPAC. Cisplatin and doxorubicin may be safely used as PIPAC at a dose of 30 mg/m(2) and 6 mg/m(2), respectively; oxaliplatin can be used at an intraperitoneal dose of 135 mg/m(2). No serious adverse event was reported. The dosages achieved to date are the highest ever used in PIPAC. The results of these investigations should be the starting point for further clinical phase II trials regarding repeated PIPAC, possibly associated with systemic chemotherapy. ABSTRACT: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an innovative laparoscopic intraperitoneal chemotherapy approach with the advantage of a deeper tissue penetration. Thus far, oxaliplatin has been administered at an arbitrary dose of 92 mg/m(2), cisplatin at 7.5 mg/m(2) and doxorubicin 1.5 mg/m(2). This is a model-based approach phase I dose escalation study with the aim of identifying the maximum tolerable dose of the three different drugs. The starting dose of oxaliplatin was 100 mg/m(2); cisplatin was used in association with doxorubicin: 15 mg/m(2) and 3 mg/m(2) were the respective starting doses. Safety was assessed according to Common Terminology Criteria for Adverse Events (CTCAE version 4.03). Thirteen patients were submitted to one PIPAC procedure. Seven patients were treated with cisplatin and doxorubicin and 6 patients with oxaliplatin; no dose limiting toxicities and major side effects were found. Common adverse events included postoperative abdominal pain and nausea. The maximum tolerable dose was not reached. The highest dose treated cohort (oxaliplatin 135 mg/m(2); cisplatin 30 mg/m(2) and doxorubicin 6 mg/m(2)) tolerated PIPAC well. Serological analyses revealed no trace of doxorubicin at any dose level. Serum levels of cis- and oxaliplatin reached a peak at 60–120 min after PIPAC and were still measurable in the circulation 24 h after the procedure. Cisplatin and doxorubicin may be safely used as PIPAC at a dose of 30 mg/m(2) and 6 mg/m(2), respectively; oxaliplatin can be used at an intraperitoneal dose of 135 mg/m(2). The dosages achieved to date are the highest ever used in PIPAC. MDPI 2021-03-03 /pmc/articles/PMC7958944/ /pubmed/33802269 http://dx.doi.org/10.3390/cancers13051060 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Robella, Manuela De Simone, Michele Berchialla, Paola Argenziano, Monica Borsano, Alice Ansari, Shoeb Abollino, Ornella Ficiarà, Eleonora Cinquegrana, Armando Cavalli, Roberta Vaira, Marco A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis |
title | A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis |
title_full | A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis |
title_fullStr | A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis |
title_full_unstemmed | A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis |
title_short | A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis |
title_sort | phase i dose escalation study of oxaliplatin, cisplatin and doxorubicin applied as pipac in patients with peritoneal carcinomatosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958944/ https://www.ncbi.nlm.nih.gov/pubmed/33802269 http://dx.doi.org/10.3390/cancers13051060 |
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