High-dose continuous-infusion ifosfamide in advanced thymic epithelial Tumors: A TYME network study.


Journal

Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805

Informations de publication

Date de publication:
02 2023
Historique:
received: 15 07 2022
revised: 13 12 2022
accepted: 06 01 2023
pubmed: 12 1 2023
medline: 8 2 2023
entrez: 11 1 2023
Statut: ppublish

Résumé

We reported the efficacy and safety results of high-dose, continuous-infusion Ifosfamide,in patients with advanced thymoma (TM) and thymic carcinoma (TC). This was a multicentric, prospective study in patients with advanced TM or TC, who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis or anti-PD(L)1 was allowed. Patients received Ifosfamide (1 g/m2/day) and sodium-2-mercaptoethanesulfonate (1 g/m2/day), as continuous infusion, via a portable pumps for 14 consecutive days. Treatment was administered every 4 weeks until progression or unacceptable toxicity, up to a maximum of 6 cycles. The primary endpoint was the overall response rate (ORR) assessed by RECIST1.1. Secondary endpoints included disease control rate (DCR), Progression-free survival (PFS), overall survival (OS), and safety. Eighteen patients were enrolled from October 2020 to January 2022. Twelve patients had a TC, 5 a TM and 1 a mixed TM/TC. Sixty-one percent of patients (11/18) had stage IVB disease according to Masaoka-Koga, and 39% (7/18) had an ECOG-PS 2. The median number of previous lines of therapy was 2 (range:1-5), and 72% (13/18) and 61% (11/18) of patients were pretreated with an anti-angiogenesis drug and an anti-PD(L)1 drug respectively. The ORR and the disease control rate (DCR) were 28 % (95 %CI: 10 %-53 %) and 67 % (95 %CI: 41 %-86 %), respectively. The median follow-up for PFS was 17.3 months (95 %CI: 4.3-NA), and median PFS was 5.4 months (95 %CI: 2.9-6.4). The median duration of response and SD was respectively 19.6 months (95 %CI: 3.5-NA) and 6.0 months (95 % CI: 3.8-6.4). In patients with TC, the ORR and DCR were 15 % (95 % CI: 2 %-45 %) and 54 % (95 % CI: 25 %-81 %), respectively. In the subgroup of 5 patients with TM, 2 PR and 3 SD were observed. Most patients had only mild (grade 1-2) AEs, the most common being nausea and vomiting (39%; 7/18) and transaminases elevation (33%; 6/18). Twenty-two percent of patients (4/18) experienced an AEs of grade 3 and required ifosfamide dose reduction. No patients had severe AEs. High-dose continuous-infusion Ifosfamide can be considered as a valuable treatment option in patients with advanced thymic epithelial tumors.

Sections du résumé

BACKGROUND
We reported the efficacy and safety results of high-dose, continuous-infusion Ifosfamide,in patients with advanced thymoma (TM) and thymic carcinoma (TC).
METHODS
This was a multicentric, prospective study in patients with advanced TM or TC, who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis or anti-PD(L)1 was allowed. Patients received Ifosfamide (1 g/m2/day) and sodium-2-mercaptoethanesulfonate (1 g/m2/day), as continuous infusion, via a portable pumps for 14 consecutive days. Treatment was administered every 4 weeks until progression or unacceptable toxicity, up to a maximum of 6 cycles. The primary endpoint was the overall response rate (ORR) assessed by RECIST1.1. Secondary endpoints included disease control rate (DCR), Progression-free survival (PFS), overall survival (OS), and safety.
RESULTS
Eighteen patients were enrolled from October 2020 to January 2022. Twelve patients had a TC, 5 a TM and 1 a mixed TM/TC. Sixty-one percent of patients (11/18) had stage IVB disease according to Masaoka-Koga, and 39% (7/18) had an ECOG-PS 2. The median number of previous lines of therapy was 2 (range:1-5), and 72% (13/18) and 61% (11/18) of patients were pretreated with an anti-angiogenesis drug and an anti-PD(L)1 drug respectively. The ORR and the disease control rate (DCR) were 28 % (95 %CI: 10 %-53 %) and 67 % (95 %CI: 41 %-86 %), respectively. The median follow-up for PFS was 17.3 months (95 %CI: 4.3-NA), and median PFS was 5.4 months (95 %CI: 2.9-6.4). The median duration of response and SD was respectively 19.6 months (95 %CI: 3.5-NA) and 6.0 months (95 % CI: 3.8-6.4). In patients with TC, the ORR and DCR were 15 % (95 % CI: 2 %-45 %) and 54 % (95 % CI: 25 %-81 %), respectively. In the subgroup of 5 patients with TM, 2 PR and 3 SD were observed. Most patients had only mild (grade 1-2) AEs, the most common being nausea and vomiting (39%; 7/18) and transaminases elevation (33%; 6/18). Twenty-two percent of patients (4/18) experienced an AEs of grade 3 and required ifosfamide dose reduction. No patients had severe AEs.
CONCLUSION
High-dose continuous-infusion Ifosfamide can be considered as a valuable treatment option in patients with advanced thymic epithelial tumors.

Identifiants

pubmed: 36630822
pii: S0169-5002(23)00008-9
doi: 10.1016/j.lungcan.2023.01.004
pii:
doi:

Substances chimiques

Ifosfamide UM20QQM95Y
Mesna NR7O1405Q9

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

98-102

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Fabio Conforti (F)

Division of Melanoma, Sarcomas and Rare Tumors, European Institute of Oncology, IRCCS Milan, Italy; Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy. Electronic address: fabio.conforti@ieo.it.

Laura Pala (L)

Division of Melanoma, Sarcomas and Rare Tumors, European Institute of Oncology, IRCCS Milan, Italy; Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy.

Grazia Vivanet (G)

Division of Early Drug Development for Innovative Therapy, European Institute of Oncology IRCCS - Milan.

Chiara Corti (C)

Division of Early Drug Development for Innovative Therapy, European Institute of Oncology IRCCS - Milan; Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy.

Chiara Catania (C)

Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan, Italy.

Daniele Maiettini (D)

Division of Interventional Radiology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Gianluca Varano (G)

Division of Interventional Radiology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Benedetta Di Venosa (B)

Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Giuseppe Curigliano (G)

Division of Early Drug Development for Innovative Therapy, European Institute of Oncology IRCCS - Milan.

Piermario Salvini (P)

Department of Oncology, Humanitas Gavazzeni, Bergamo, Italy.

Rossana Berardi (R)

Medical Oncology, AOU Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Polytechnic University of the Marche Region, Ancona.

Zelmira Ballatore (Z)

Medical Oncology, AOU Ospedali Riuniti Umberto I - GM Lancisi - G Salesi - Ancona.

Tommaso Martino De Pas (TM)

Division of Melanoma, Sarcomas and Rare Tumors, European Institute of Oncology, IRCCS Milan, Italy; Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy.

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