Figures
- FIGURE 1
Devices used for bronchoscopic intratumoural injection. a) A conventional transbronchial needle was used for injection of several types of chemotherapy by Celikoglu et al. [17] among others [16, 18–25, 27, 31, 32]. b) An endobronchial ultrasound-guided transbronchial needle was used for injection of cisplatin by several investigators [26, 29, 30, 34, 48–50]. c) A novel transbronchial microcatheter (Blowfish catheter; Mercator MedSystems Inc, Emeryville, CA, USA) was used to inject paclitaxel into endobronchial lesions following standard recanalisation techniques [33]. Images in (a) and (b) are courtesy of the authors; (c) was modified from [33] with permission from publisher.
- FIGURE 2
Bronchoscopic intratumoural injection using a conventional transbronchial needle. This technique has been used by several groups for endobronchial intratumoural chemotherapy (EITC) [16–25, 27, 31, 32]. Image modified from [70] under Creative Commons Attribution 2.5 license.
Tables
- TABLE 1
Intratumoural therapies delivered via bronchoscopic injection in non-small cell lung cancer
Therapy References Bacillus Calmette–Guerin (BCG)# [12–14] Nocardia rubra cell wall cytoskeleton# [45] OK-432 [46] Ethanol (99.5%) [47] 5-Fluorouracil [17, 19] Mitomycin [17] Methotrexate [17] Bleomycin [17] Mitoxantrone [17] Cisplatin# [20, 21, 25–29, 34, 48–50] Carboplatin [18] Paclitaxel [30, 33] Para-toluenesulfonamide [31, 32] Recombinant viral vector# [35–44] Gene-modified dendritic cells# [51] #: Used bronchosopic and percutaneous injection.
- TABLE 2
Ongoing trials of intratumoural therapies for non-small cell lung cancer listed on ClinicalTrials.gov
Therapy Phase Site Tumour types Key outcome(s) ClinicalTrials.gov ID Title AdV-tk (aglatimagene besadenovec)+valacyclovir I Intratumoural bronchoscopic injection NSCLC Primary: Safety
Secondary: Immunologic changes, PFS, OSNCT03131037 Intratumoural gene-mediated cytotoxic immunotherapy in patients with resectable NSCLC CCL21 gene-modified dendritic cell with pembrolizumab I Bronchoscopic or CT-guided intratumoural injection NSCLC Primary: Maximum tolerated dose, objective response rate
Secondary: Adverse events, PD-L1 expressionNCT03546361 Intratumoural administration of CCL21 gene-modified dendritic cell with intravenous pembrolizumab for advanced NSCLC Intratumoural G100 with atezolizumab and radiotherapy II Intratumoural bronchoscopic injection NSCLC
Pancreatic cancer
Virus-associated tumours
Melanoma
Bladder cancer
Triple-negative breast cancerPrimary: Response by RECIST 1.1
Secondary: Adverse events, tumour immune cells, blood cytokines, lymphocytes and kynurenineNCT03915678 Atezolizumab combined with intratumoural G100 And immunogenic radiotherapy in patients with advanced solid tumours (AGADIR) Intratumoural ilixadencel with pembrolizumab I/II Intratumoural# NSCLC
Squamous cell carcinoma of head and neck
Gastric adenocarcinomaPrimary: Adverse events, objective response rate
Secondary: Objective response rate, CD8 T cell response by flow cytometry, overall survival, progression free survivalNCT03735290 Study to evaluate the safety and effectiveness of ilIxadencel administered into tumours in combination with checkpoint inhibitor in patients with advanced cancer (ILIAD) Oncolytic adenovirus (CAdVEC) and T cells (HER2-AdVST) I Intratumoural# Lung cancer
Bladder cancer
Squamous cell carcinoma of head and neck
Cancer of the salivary gland
Breast cancer
Gastric cancer
Oesophageal cancer
Colorectal cancer
Pancreatic adenocarcinomaPrimary: Maximum tolerated dose
Secondary: Response by RECIST 1.1, PFS, OS, adverse eventsNCT03740256 Binary oncolytic adenovirus in combination with HER2-specific chimeric antigen receptor modified cytotoxic T cells in advanced HER2 positive solid tumours (VISTA) INT230-6 I/II Intratumoural# Lung cancer
Melanoma
Head and neck cancer
Lymphoma
Breast cancer
Pancreatic cancer
Liver cancer
Colon cancer
Glioblastoma
Bile duct cancer
Ovarian cancer
Sarcoma
Squamous cell carcinomaPrimary: Adverse events
Secondary: Efficacy, pharmacokinetics and pharmacodynamicsNCT03058289 Phase 1/2 safety study of intratumourally dosed INT230-6 (IT-01) Intratumoural ABBV-927 with or without ABBV-181 I Intratumoural# NSCLC
Squamous cell carcinoma of head and neck
Advanced solid tumoursPrimary: Maximum tolerated dose, pharmacokinetics and pharmacodynamics
Secondary: Clinical benefit rate, objective response rate, PFSNCT02988960 Study of ABBV-927 and ABBV-181, an immunotherapy, in subjects with advanced solid tumours Clostridium novyi-NT I Intratumoural# Advanced solid tumours Primary: Maximum tolerated dose
Secondary: Response by RECIST 1.1NCT03435952 Pembrolizumab with intratumoural injection of Clostridium novyi-NT NSCLC: non-small cell lung cancer; PFS: progression-free survival; OS: overall survival; RECIST: Response Evaluation Criteria In Solid Tumours. #: Method of intratumoural injection not specified or includes percutaneous injection.
Jump To
- Article
- Abstract
- Abstract
- Introduction
- History of intratumoural therapies for cancer
- Advantages of local therapies for cancer
- Understanding the tumour microenvironment
- Devices for injection
- Recent trials in bronchoscopic intratumoural injection
- Pharmacokinetics and pharmacodynamics
- Safety
- Future directions
- Conclusions
- Footnotes
- References
- Figures & Data
- Info & Metrics