Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols

Background  Peg-GCSF has similar efficacy at a dose of 60 µg/kg and 100 µg/kg. The conventional 6 mg SC dose was based on the maximum tolerable dose. In Japan, 3.6 mg dose was approved on the basis of dose finding studies. Peg-GCSF is an integral part of dose-dense chemotherapy protocols. Dose findi...

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Autores principales: Patel, Amol, Pathak, Abhishek, Sarin, Arti, Shelly, Divya, Ranjan, Richa, Singh, Arashdeep, Kala, Tripti, PV, Babitha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Thieme Medical and Scientific Publishers Pvt. Ltd. 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691905/
https://www.ncbi.nlm.nih.gov/pubmed/38047054
http://dx.doi.org/10.1055/s-0042-1757599
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author Patel, Amol
Pathak, Abhishek
Sarin, Arti
Shelly, Divya
Ranjan, Richa
Singh, Arashdeep
Kala, Tripti
PV, Babitha
author_facet Patel, Amol
Pathak, Abhishek
Sarin, Arti
Shelly, Divya
Ranjan, Richa
Singh, Arashdeep
Kala, Tripti
PV, Babitha
author_sort Patel, Amol
collection PubMed
description Background  Peg-GCSF has similar efficacy at a dose of 60 µg/kg and 100 µg/kg. The conventional 6 mg SC dose was based on the maximum tolerable dose. In Japan, 3.6 mg dose was approved on the basis of dose finding studies. Peg-GCSF is an integral part of dose-dense chemotherapy protocols. Dose finding and scheduling study of peg-GCSF have not been conducted in Indian patients. Materials and Methods  We conducted two-center phase 1/2 clinical study addressing the timing and efficacy of peg-GCSF in Indian breast cancer patients (CTRI no: 2021/07/034751). Three groups of timing administration were studied, namely 1, 6, and 24 hours post chemotherapy. The phase 2 part was the expansion of the best timing group. The primary objective was dose density, which was defined as receiving chemotherapy on < 3 days of scheduled date. Adriamycin/epirubicin cyclophosphamide (AC/EC) was administered q2 weeks. The total leucocyte (TLC) and absolute neutrophil (ANC) kinetics were studied. Other outcomes were incidence of grade 4 neutropenia, febrile neutropenia (FN), and requirement of additional doses of G-CSF. Bone pain, fever, and myalgia were studied for adverse effects. Results  From November 20 to December 21, 36 patients were enrolled. Patient characteristics are depicted in Table 1. Initially, three patients received the peg-GCSF in each timing group. One patient in each 1-hour and 6 hours needed G-CSF support for maintaining the dose density. The 24-hour group was carried to phase 2 part. Dose density was maintained in 97% of patients. None of the patient in 24-hour group had FN. Also, 4/30 patients had grade 4 neutropenia and required an additional dose of GCSF. Grade 3 or 4 bone pain was not noticed by any of the patients. During the first cycle, the mean ANC (cells/μL) was 5284, 20704, 3010, 6954 on D0, D + 3, D + 7, and D + 13, respectively (Fig. 1A-TLC and 1B-ANC). The mean ANC (cells/μL) rise on D + 3 in cycles 1, 2, 3, 4 was 23810, 29209, 32428,22455, respectively. Conclusion  Dose density of AC/EC breast cancer protocol is maintained with peg-GCSF 3 mg. Post chemotherapy 24-hour timing of peg-GCSF administration remains as the standard. A phase 3 trial of 6 mg versus 3 mg is warranted.
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spelling pubmed-106919052023-12-02 Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols Patel, Amol Pathak, Abhishek Sarin, Arti Shelly, Divya Ranjan, Richa Singh, Arashdeep Kala, Tripti PV, Babitha South Asian J Cancer Background  Peg-GCSF has similar efficacy at a dose of 60 µg/kg and 100 µg/kg. The conventional 6 mg SC dose was based on the maximum tolerable dose. In Japan, 3.6 mg dose was approved on the basis of dose finding studies. Peg-GCSF is an integral part of dose-dense chemotherapy protocols. Dose finding and scheduling study of peg-GCSF have not been conducted in Indian patients. Materials and Methods  We conducted two-center phase 1/2 clinical study addressing the timing and efficacy of peg-GCSF in Indian breast cancer patients (CTRI no: 2021/07/034751). Three groups of timing administration were studied, namely 1, 6, and 24 hours post chemotherapy. The phase 2 part was the expansion of the best timing group. The primary objective was dose density, which was defined as receiving chemotherapy on < 3 days of scheduled date. Adriamycin/epirubicin cyclophosphamide (AC/EC) was administered q2 weeks. The total leucocyte (TLC) and absolute neutrophil (ANC) kinetics were studied. Other outcomes were incidence of grade 4 neutropenia, febrile neutropenia (FN), and requirement of additional doses of G-CSF. Bone pain, fever, and myalgia were studied for adverse effects. Results  From November 20 to December 21, 36 patients were enrolled. Patient characteristics are depicted in Table 1. Initially, three patients received the peg-GCSF in each timing group. One patient in each 1-hour and 6 hours needed G-CSF support for maintaining the dose density. The 24-hour group was carried to phase 2 part. Dose density was maintained in 97% of patients. None of the patient in 24-hour group had FN. Also, 4/30 patients had grade 4 neutropenia and required an additional dose of GCSF. Grade 3 or 4 bone pain was not noticed by any of the patients. During the first cycle, the mean ANC (cells/μL) was 5284, 20704, 3010, 6954 on D0, D + 3, D + 7, and D + 13, respectively (Fig. 1A-TLC and 1B-ANC). The mean ANC (cells/μL) rise on D + 3 in cycles 1, 2, 3, 4 was 23810, 29209, 32428,22455, respectively. Conclusion  Dose density of AC/EC breast cancer protocol is maintained with peg-GCSF 3 mg. Post chemotherapy 24-hour timing of peg-GCSF administration remains as the standard. A phase 3 trial of 6 mg versus 3 mg is warranted. Thieme Medical and Scientific Publishers Pvt. Ltd. 2023-08-11 /pmc/articles/PMC10691905/ /pubmed/38047054 http://dx.doi.org/10.1055/s-0042-1757599 Text en MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.
spellingShingle Patel, Amol
Pathak, Abhishek
Sarin, Arti
Shelly, Divya
Ranjan, Richa
Singh, Arashdeep
Kala, Tripti
PV, Babitha
Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols
title Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols
title_full Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols
title_fullStr Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols
title_full_unstemmed Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols
title_short Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols
title_sort phase 1/2 study of the timing and efficacy of 3 mg peg-gcsf in neo/adjuvant dose dense breast cancer treatment protocols
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691905/
https://www.ncbi.nlm.nih.gov/pubmed/38047054
http://dx.doi.org/10.1055/s-0042-1757599
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