Chemotherapy for Late-Stage Cancer Patients: Meta-Analysis of Complete Response Rates

Complete response (CR) rates reported for cytotoxic chemotherapy for late-stage cancer patients are generally low, with few exceptions, regardless of the solid cancer type or drug regimen.

We investigated CR rates reported in the literature for clinical trials using chemotherapy alone, across a wide range of tumour types and chemotherapeutic regimens, to determine an overall CR rate for late-stage cancers.

The Immune System and Responses to Cancer: Coordinated Evolution

This review explores the evolutionary interaction and co-development between immune system and somatic evolution.

Over immense durations, continuous interactions between microbes, aberrant somatic cells, including malignant cells, and the immune system have successively shaped the evolutionary development of the immune system, somatic cells and microorganisms through continuous adaptive symbiotic processes of progressive immunological and somatic change providing what we observe today.

biotempus-publications-1

The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses

This year marks the twentieth anniversary of the approval by the US Food and Drug Administration of interleukin-2 (IL2) for use in cancer therapy, initially for renal cell carcinoma and later for melanoma.

biotempus-publications-2

Biorhythmic fluctuation of systemic immunity in melanoma

Evidence suggests that immunological response in chronic inflammation is dynamic, oscillating between active immunity and tolerance. We hypothesized that a similar dynamic exists in melanoma and administration of therapy during a unique phase of such oscillation could impact clinical outcome.

biotempus-publications-7

Timed Ablation of Regulatory CD4+ T Cells Can Prevent Murine AIDS Progression

Over 50 years of cancer therapy history reveals complete clinical responses (CRs) from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies) for advanced solid malignancies occur with an approximately similar frequency of 5%–10%.

biotempus-publications-6

Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

Over 50 years of cancer therapy history reveals complete clinical responses (CRs) from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies) for advanced solid malignancies occur with an approximately similar frequency of 5%–10%.

biotempus-publications-9

CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?

The search for a suitable biomarker which indicates immune system responses in cancer patients has been long and arduous, but a widely known biomarker has emerged as a potential candidate for this purpose. C-Reactive Protein (CRP) is an acute-phase plasma protein that can be used as a marker for activation of the immune system.


In the Media

biotempus-publications-4

Window of Opportunity – Australasian Science

It is just over 100 years since Charles Mayo, of Mayo Clinic fame, was exchanging letters with William Coley, a New York surgeon who was using “bacterial toxin” vaccines to successfully treat patients with advanced cancer – even causing complete remission of all cancer in 5-10% of patients.

biotempus-publications-3

A Matter of Time – Australasian Science

Not all cancer patients are cured by chemotherapy, biological therapies, radiotherapy or surgery. Some patients can have complete regression of all cancer, while others do not appear to be responding or show some level of clinical response but not enough to overcome the tumour.

biotempus-publication-10

Simpler is often better when battling the Big C

Expensive drug therapies are mopping up health budgets but many may be of little real benefit.

Within next 10 to 15 years it is predicted that Australian federal and state budgets will be totally consumed by the expanding cost of healthcare.


Conference Poster Presentations

Serial measurements of serum C-Reactive Protein (CRP) oscillate in cancer patients. Can CRP be used as a surrogate biomarker for immune regulation? Cancer Research Institute Conference, New York USA September 2006.

Description: First conference presented work of serial serum data over 4 weeks in late stage cancer patients using High Sensitive C-Reactive Protein, cytokines and immune cell phenotyping. This also puts forward the hypothesis that this represents the patient’s immune response is homeostatically oscillating and that the timing of therapy with respect to this cycle could affect therapeutic outcome.

Breaking a Deadly Cycle: Successful Timed Treg Lymphodepletion. Is it Already Accidentally Happening in the Oncology Clinic with Standard Drugs? NCI Keystone conference: ‘Potent new cancer Immunotherapies’. Banff Canada April 2007.

Description: This was an invited oral and poster presentation and for the first time uses the indirect evidence (via clinical trial meta- analysis) showing that the complete response (CR) rates across various cancers and chemotherapy drugs hovers around on average the 7% mark. In addition, this ~7% barrier is due to the random administration of cytotoxic agents accidentally ablating synchronously dividing regulatory T cells within an approximate 7 day repeating immune cycle.

Improving Vaccine and Chemotherapies for Advanced Melanoma and Ovarian Cancer. Understanding Immune System Kinetics to Better Time Treatment. Society for Immunotherapy for Cancer of Cancer (SITC), Washington DC USA, 2009.

Description: A poster presented at the Society for Immunotherapy of Cancer (SITC) in Washington DC 2009. Discusses actual patient examples of serial blood biomarker (Hs-CRP) monitoring the immune cycle and the timed application of vaccine therapy and chemotherapy in late stage melanoma and ovarian cancer. In addition, this discuses treatment outcomes and potential costs and cost savings using this approach.

Immune Therapies for Cancer: Bimodality – The Blind Spot to Clinical Efficacy – Lost in Translation. Society for Immunotherapy for Cancer of Cancer (SITC), Washington DC USA, 2011.

Description: A poster presented at the Society for Immunotherapy of Cancer (SITC) in Washington DC 2011. Discusses how various agents return a clinical response spectrum with a minority of complete responses. In addition, the bimodality of certain cytokines /receptors and immune cell types. In particular, discusses IL2 complete response rate meta-analysis showing how the CR rate hovers around ~7% in late stage melanoma and Renal Cell Carcinoma.

Mathematical Modelling of Immune Kinetics in Advanced Cancer through Meta-Analysis of Complete Response Rates: Immune Synchronization Emerges as the Likely Determinant of Clinical Response. Society for Immunotherapy for Cancer of Cancer (SITC), Washington DC USA, 2013.

Description: One of two posters presented at the Society for Immunotherapy of Cancer (SITC) in Washington DC 2013. This important piece of work mathematically links compete response rate (with various agents) to a recurring therapeutic window within a repeating / oscillating immune cycle. The meta analysis shows how the CR rate hovers around ~7% . This relationship and probability of achieving a complete response is the result of a conjunction of immunologic events of the patient being treated on the right day in their approximate 7 day immune cycle. This mathematical equation called, The Complete Response Probability Equation was derived from data collected in 9,964 patients in 160 trials

Clinical Outcomes of Interleukin-2 Therapy in Advanced Cancer: Meta-Analysis of over 60 Trials. Society for Immunotherapy for Cancer of Cancer (SITC), Washington DC USA, 2013.

Description: Second of two posters presented at the Society for Immunotherapy of Cancer (SITC) in Washington DC 2013. This work focuses on a meta-analysis from 60 trials (5312 patients) in patients with late stage disease using IL2 as monotherapy or multi-agent combinations. The meta-analysis shows how the IL2 monotherapy CR rate hovers around ~7% and is represented nicely as a scatterplots of actual clinical CR data and compares a 14 sided dice probability simulation of running the equivalent number of trials and is based mathematically on the The Complete Response Probability Equation. Remarkably the scatterplots show similar dispersion.