Related Experiment Video
Updated: Jun 13, 2026
Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
Molecular Subtype-Associated Response to Cyclophosphamide-Epirubicin-Cisplatin Regimen in Recurrent or Metastatic
Wenbo Tang1, Jiuli Zhou1, Wei Zhao1
1Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200123, China.
Background/Objectives:
Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) has no standard systemic therapy. VEGFR-targeting tyrosine kinase inhibitors (TKIs) are commonly used first-line, though no international standard exists; cisplatin-based chemotherapy is an alternative. We retrospectively reviewed the cyclophosphamide-epirubicin-cisplatin (CEP) regimen to determine whether prior TKI exposure compromises subsequent chemotherapy efficacy.
Methods:
We studied 31 patients given CEP for progressive R/M ACC (2018-2023). Tumor response was assessed by RECIST 1.1. Molecular subtype was determined by c-MYC/p63 immunohistochemistry (ACC-I, c-MYC-positive/p63-negative; ACC-II, p63-positive/c-MYC-low or negative). Multivariable models used Firth's penalized likelihood Cox regression. Next-generation sequencing (NGS) was available in 21 of 31 patients.
Results:
Thirty-one patients were enrolled (median age 48; 17 [54.8%] with prior TKI). At median follow-up of 22.6 months, the objective response rate (ORR) was 19.4%, disease control rate 71.0%, median progression-free survival (PFS) 5.3 months, and median overall survival (OS) 10.3 months. Prior TKI did not lower efficacy: ORR 17.6% vs. 21.4%, PFS hazard ratio 0.76 (p = 0.519). All six partial responses occurred in ACC-I tumors (35.3% vs. 0% in ACC-II, p = 0.021). In the NGS subset (5 PIK3CA-mutant), PIK3CA mutation (OS HR 6.19, p = 0.024) and bone metastasis (OS HR 5.84, p = 0.027) remained associated with shorter OS after adjustment. No treatment-related deaths occurred.
Conclusions:
CEP is active in R/M ACC, and prior TKI exposure did not appear to reduce efficacy. Higher response rates in ACC-I tumors and the apparent PIK3CA-related survival deficit are exploratory observations that need prospective testing before they can guide treatment.
Insights
Cyclophosphamide-epirubicin-cisplatin (CEP) chemotherapy is effective for recurrent or metastatic adenoid cystic carcinoma (R/M ACC). Prior tyrosine kinase inhibitor (TKI) use did not reduce CEP efficacy in this study.
Area of Science:
- Oncology
- Medical Oncology
- Cancer Therapeutics
Background:
- Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) lacks a standard systemic therapy.
- Tyrosine kinase inhibitors (TKIs) targeting VEGFR are common first-line treatments, but efficacy of subsequent chemotherapy is unclear.
- The cyclophosphamide-epirubicin-cisplatin (CEP) regimen is an alternative chemotherapy option.
Purpose of the Study:
- To evaluate the efficacy of the CEP regimen in patients with R/M ACC.
- To determine if prior exposure to TKIs impacts the effectiveness of subsequent CEP chemotherapy.
- To explore potential associations between molecular subtypes and treatment outcomes.
Main Methods:
- Retrospective review of 31 patients with R/M ACC treated with CEP between 2018-2023.
- Tumor response assessed using RECIST 1.1 criteria.
- Molecular subtyping (ACC-I vs. ACC-II) via c-MYC/p63 immunohistochemistry; next-generation sequencing (NGS) performed on a subset.
Main Results:
- The CEP regimen showed an objective response rate (ORR) of 19.4% and a disease control rate of 71.0%.
- Prior TKI exposure did not significantly affect ORR or progression-free survival (PFS).
- Higher response rates were observed in ACC-I tumors (35.3% vs. 0% in ACC-II). PIK3CA mutations and bone metastasis were associated with shorter overall survival (OS).
Conclusions:
- The CEP regimen demonstrates activity in R/M ACC, irrespective of prior TKI treatment.
- Higher response rates in ACC-I tumors and the impact of PIK3CA mutations on survival warrant further investigation.
- Prospective studies are needed to validate these exploratory findings and guide clinical treatment decisions.