Trial Demonstrates Efficacy of Injecting Bacterial Spores Into Resistant Cancerous Tumors

MedicalResearch.com Interview with:

Filip Janku, MD, PhD Associate Professor, Investigational Cancer Therapeutics (Phase I Clinical Trials Program) Center Medical Director, Clinical and Translational Research Center The University of Texas MD Anderson Cancer Center Houston, TX 77030

Dr. Janku

Filip Janku, MD, PhD
Associate Professor, Investigational Cancer Therapeutics
(Phase I Clinical Trials Program)
Center Medical Director, Clinical and Translational Research Center
The University of Texas MD Anderson Cancer Center
Houston, TX 77030

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Clostridium novyi-NT is an attenuated strain of bacteria Clostridium, which induced a microscopically precise, tumor-localized response in a rat brain tumor model and in companion dogs bearing spontaneous cancers. Clostridium novyi-NT can only grow in hypoxic (low-oxygen) tumor environment and destroys cancer cells by secreting lipases, proteases, and other hydrolytic enzymes; recruiting inflammatory cells to tumors eliciting anti-tumor immune responses in animals. Furthermore, intratumoral injection can plausibly induce an immune mediated abscopal effect in non-injected tumor sites.

Therefore, we designed a phase I dose-finding study to test for safety and tolerability of the single intratumoral injection of Clostridium novyi-NT in 24 patients with advanced cancers with no available standard therapies. We also designed experiments to study activation of antitumor immune response in blood and tumor samples from patients undergoing the therapy.

We demonstrated that single dose of intratumoral injection of Clostridium novyi-NT is feasible and has led to significant destruction of injected tumor masses. Adverse events, which were often related to the tumor destruction at the infected site, could have been significant but mostly manageable. Correlative studies of pre-treatment and post-treatment tumor and blood samples suggested immune response to therapy.

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Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy

MedicalResearch.com Interview with:

Kelly K. Hunt, MD Department of Breast Surgical Oncology The University of Texas MD Anderson Cancer Center Houston

Dr. Hunt

Kelly K. Hunt, MD
Department of Breast Surgical Oncology
The University of Texas MD Anderson Cancer Center
Houston

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We completed a neoadjuvant trial at MD Anderson Cancer Center and published the results in 2005 demonstrating that trastuzumab delivered in combination with anthracycline and taxane based chemotherapy resulted in pathologic complete response rates of up to 60% in patients with HER-2 positive breast cancer. This was a single institutions study and there was concern about cardiac toxicity when using anthracyclines and trastuzumab concurrently.

We therefore worked with the NCI cooperative groups, the American College of surgeons oncology group (ACOSOG), to design the ACOSOG Z1041 trial. This trial compared to different regimens in the neoadjuvant setting, one regimen utilizing concurrent anthracycline and taxanes based chemotherapy with trastuzumab and the other regimen utilizing concurrent taxanes with trastuzumab but the anthracycline was delivered in a sequential fashion.

The primary end point of the trial was pathologic complete response rates in the breast.

The results from this primary end point were published in the Lancet Oncology in 2013 and showed that the pathologic complete response rates were the same with the 2 different regimens. This was important since patients could be assured of similar efficacy without the potential added toxicity of delivering anthracyclines and trastuzumab together.

The current publication is a report of the disease-free and overall survival rates from the Z1041 trial. Several studies have shown an association between pathologic complete response rates and survival. The current study shows that there is no difference in survival rates between the 2 different regimens. So once again there is an association between pathologic complete response and survival and it is not important that the anthracycline and trastuzumab are given concurrently in order to achieve these high pathologic complete response rates and improve survival rates. Continue reading