An iron-based injection inspired by wastewater treatment has shown early signs of activity against advanced cancer in a small clinical trial in China. The experimental therapy controlled disease in 16 of 19 patients, including two whose tumors shrank.
The Phase I study tested the injection directly inside tumors in patients whose cancers had progressed despite previous treatment.
Its 84.2 percent disease control rate includes both stable disease and tumor shrinkage. The objective response rate, which measures shrinkage, was 10.5 percent.
Published on October 1 in Signal Transduction and Targeted Therapy, the study was conducted at three hospitals in Sichuan, Hubei and Shandong provinces.
A Phase II trial involving 52 patients is now underway across 10 Chinese hospitals to further assess safety and efficacy.
The wastewater chemistry
The approach draws on a chemical reaction used to treat industrial wastewater. Iron reacts with hydrogen peroxide to generate hydroxyl radicals, highly reactive molecules that can break down organic pollutants.
Researchers adapted that principle to attack malignant cells. They combined a clinically approved nanocrystalline carbon injection with ferrous sulfate to produce a formulation called CNSI-Fe.
The treatment is designed to induce ferroptosis, a form of cell death involving iron-dependent damage to cell membranes. Normal cells have antioxidant defenses, including glutathione, that help protect against this damage.
Previous animal experiments showed that CNSI-Fe inhibited tumour growth in six tumour models, including colorectal, breast and pancreatic cancer. The clinical trial examined whether that approach could translate into treatment for people with refractory solid tumors.
What the trial found in patients
The 19 participants had several cancer types, including sarcoma, head and neck cancer, pancreatic cancer, non-small-cell lung cancer, ovarian cancer, breast cancer and vulval cancer.
Sixteen had stage IV metastatic disease. All had received at least two previous lines of systemic therapy.
Physicians administered different doses directly into tumor sites and assessed responses in both injected tumors and lesions elsewhere in the body. The injected target lesions responded better than the overall collection of lesions assessed throughout the body.
The formulation remained stable for six hours after preparation, while serum iron levels peaked within half an hour of administration.
“Overall, CNSI-Fe demonstrated a favorable safety profile and promising antitumor activity,” wrote Professor Wang Yongsheng, the trial’s lead principal investigator at West China Hospital.
Side effects and the next testing stage
Injection pain was the most common adverse reaction, affecting 89.5 percent of participants, followed by hypertension in 52.6 percent. One patient withdrew because of a hypersensitivity reaction.
The researchers reported no severe hematological toxicity or liver and kidney toxicity. However, the small, single-arm study had no comparison group, limiting what its findings can establish about treatment effectiveness.
“CNSI-Fe administered by 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,” Wang added.
The ongoing Phase II study expands testing, but larger, controlled trials remain necessary to determine whether these early findings translate into a reliable benefit for patients.