- The iron-based injection showed early activity against advanced cancer in a small clinical trial.
- There was an 84.2% disease control rate among 19 patients, including tumor shrinkage.
- The therapy is based on a chemical reaction used in industrial wastewater treatment that induces ferroptosis.
- A Phase II trial is currently underway to further assess safety and efficacy.
An iron-based injection inspired by wastewater treatment has demonstrated early activity against advanced cancer in a small clinical trial in China. The experimental therapy controlled disease progression in 19 patients, including two with tumor shrinkage. This Phase I study directly tested patients with tumors that had progressed after prior treatments. The 84.2% disease control rate includes stable disease and tumor shrinkage. The objective response rate (the proportion of tumor shrinkage) was 10.5%. The study was published on October 1 in the journal Signal Transduction and Targeted Therapy and was conducted in three hospitals across Sichuan, Hubei, and Shandong provinces.
Progress of Phase II Trial
A Phase II trial is currently underway in 10 hospitals in China, involving 52 patients, to further assess safety and efficacy.
The method draws inspiration from a chemical reaction used to treat industrial wastewater. Iron reacts with hydrogen peroxide to generate hydroxyl radicals, highly reactive molecules capable of breaking down organic pollutants. Researchers adapted this principle to target malignant cells. They combined a clinically approved nanocrystal carbon injection with ferrous sulfate to create a formulation called CNSI-Fe. The treatment aims to induce iron-dependent cell death, known as ferroptosis, a form of cell death involving membrane damage. Normal cells possess antioxidant defense mechanisms, including glutathione, to help resist such damage.
Previous animal experiments showed that CNSI-Fe inhibited tumor growth in six tumor models, including colorectal cancer, breast cancer, and pancreatic cancer. The clinical trial examined whether this approach could translate into treatment for patients with refractory solid tumors.
Patient Background in Clinical Trial
The 19 participants included various cancer types, such as sarcoma, head and neck cancer, pancreatic cancer, non-small cell lung cancer, ovarian cancer, breast cancer, and vulvar cancer. Sixteen patients had stage IV metastatic disease. All patients had undergone at least two prior systemic treatments. Doctors directly injected different doses into the tumor sites and assessed the response of the injected tumors and lesions in other parts of the body. The response of the target lesions was better than the overall assessment of lesions in the body. The formulation remained stable for six hours after preparation, with serum iron levels peaking within half an hour of administration. "Overall, CNSI-Fe showed good safety and promising antitumor activity," said Professor Wang Yongsheng, the chief investigator at Xihua Hospital.
Injection pain was the most common adverse reaction, affecting 89.5% of participants, followed by hypertension in 52.6%. One patient withdrew due to an allergic reaction. Researchers reported no severe hematologic toxicity or hepatotoxicity. However, the small single-arm study lacked a control group, limiting the establishment of its findings regarding treatment efficacy. "CNSI-Fe administered via intratumoral injection is effective for treating ferroptosis-sensitive solid tumors, but this single-arm study has limitations and requires further evaluation through randomized Phase II/III trials," Professor Wang added.
The ongoing Phase II study expands the testing scope but still requires larger controlled trials to determine whether these early findings can translate into reliable benefits for patients.
Potential and Challenges of Iron-based Injection
This study demonstrates the potential of the iron-based injection CNSI-Fe in treating advanced cancer, particularly its ability to induce ferroptosis. While preliminary results show a good disease control rate, the reliability of these results still needs further validation due to the lack of a control group. As the Phase II trial progresses, researchers hope to confirm the safety of this therapy and its actual benefits for patients. The success of this innovative treatment could provide new options for patients with refractory cancers and advance the development of cancer therapies.