The cell behavior that the investigators regard as "malignant," including: cell autonomy;
invasion and digestion of surrounding normal tissues; migration and colonization of distant
organs; ability to develop resistance to drugs, temperature, or radiation; and ability to
kill the host, are not only characteristics of cancer cells, but of pathogenic and/or
opportunistic unicellular organisms (bacteria, fungi and protozoa). Rudolf Virchow
(1821-1902), the father of modern pathology, first pointed out the resemblance between the
biological behavior of cancer cells and that of single-celled organisms when causing
infections. He thought, incorrectly, that cancer cells were cells infected with bacteria and
had acquired their pathogenic behavior from them. Others later postulated that the behavior
of cancer cells was likely due to the re-expression of past traits and behaviors (atavism)
derived from their past evolutionary experience as independent, single-celled organisms from
which all cells in multicellular organisms originated. In other words, the behavior of
pathogenic unicellular organisms, including: unlimited replicative potential; capacity for
invasion, migration, and metastases; abilities to evade the host's immune system, to generate
multi-drug resistance; and to kill a host, are what the investigators define as "cancer" when
one of the investigators cells re-express these past ancestral traits. This reversion or
de-evolution of a differentiated cell to its ancestral undifferentiated, unicellular form has
been named "Atavistic Metamorphosis."
This does not imply that cancer cells are bacteria, protozoa, or yeasts. It means that cancer
cells express functions and/or behaviors similar to their ancestral parents, the unicellular
organisms from which our cells originated.
If this is true, a combination of drugs that are effective to eradicate certain unicellular
organisms may work in cancer treatment.
The principal objective of this study is to determine whether there is a benefit for patients
with advanced, metastatic and terminal cancers to be treated with combinations of selected
drugs conventionally used in medical practice to kill bacterial, fungal and protozoal cells.
This is an investigator initiated, randomized, single-blind, response-adaptive trial
conducted at two sites in patients who have tried conventional therapy and failed or have
refused conventional therapy. This study is being conducted to determine the efficacy of
combinations of marketed drugs against unicellular organisms in cancer treatment. The
products under investigation include FDA- and SSA-approved anti-bacterial, anti-fungal and
anti-protozoan drugs with documented anti-cancer properties. The drugs under study are
compatible with each other, and used at pharmacological dosages known to be tolerable and
safe in humans and/or cancer patients with limited adverse effects. Patients receive
treatment for 10 to 12 months. The duration of treatment is depended on the drugs
investigated. It is hypothesized that regression will occur within 6 months and treatment
will be continued with the assumption that this may prevent recurrences. Outcomes will be
measured objectively and assessments appropriate for the type of cancer treated. Outcome
measures may include 1) Changes in signs and symptoms; (2) Visual inspection of tumors using
weekly photographs and measurements (as appropriate); (3)Monthly chest X-rays to monitor lung
tumors, lung metastases and/or fluid in the chest; (4) Ultrasound to evaluate abdominal
tumors (e.g., liver metastases), and breast and armpit lymph nodes; (5) CT, MRI and PET
scans; (6) Tumor markers in blood such as Carcinoembryonic Antigen (CEA), CA-15.3, CA-19-9,
etc. and other laboratory studies to monitor response. The overall goal of this study is to
understand the efficacy of atavistic chemotherapy that may mediate metastatic or terminal
cancer regression or cure.
- Patients with malignant disease confirmed histologically that is considered
untreatable, progressive and fatal within the next 16 months.
- Patient with an expectation of life greater than 3 months.
- Patients with malignant disease that may be evaluated or measured clinically either
through radiographic studies, visually, histologically, in serum or blood tumor
markers, or through any other method medical approved for that disease.
- Patients over 75 years of age.
- Patients who are pregnant.
- Patients that have a known allergy to any of the drugs planned for use.
- Patients with renal, hepatic, pulmonary, cardiovascular compromise, or other systemic
or other clinical conditions such as AIDS, tuberculosis, etc., which, in the opinion
of the Investigator, may pose a risk to the subject.
- Malignancies of hemato-lymphatic origin (leukemias and lymphomas)