The clinical priority at the Lentz Practice is to attain long lasting disease remission in patients suffering from inoperable malignancies. The staff consists of highly skilled physicians and scientists supported by a devoted group of nurses, technologists, therapists and administrators. Itís increasingly clear that a significant percentage of human cancers are immunogenic and, under the proper physiologic conditions, the patientís immune system can successfully deal with the cancer.

Generally less than 20% of patients with metastatic solid tumor malignancies show significant tumor regression using chemotherapy, which, like surgery and radiation, fails to address the immunosuppressive nature of the disease. In addition, myelosuppressive chemotherapy and radiation therapy can impair the patientís immune response and further weaken his or her resistance to cancer. Clearly a more effective class of systemic therapies is needed.

The OncoPherese device filters immune inhibitors from patient plasma.
The OncoPherese device filters immune inhibitors from patient plasma.
The OncoPherese device filters immune inhibitors from patient plasma.
OncoPherese involves the physical removal of solubolized TNF-receptors and related inhibitors from the blood, reversing a universal mechanism by which cancer suppresses the immune response, thus allowing the patientís immune system to destroy cancer cells as it should, restoring normal immunologic homeostasis. OncoPherese is already producing superior response rates to chemotherapy in many patients.

Long-term questions naturally exist and should be addressed even as the therapy is refined and made more widely available. What is the precise efficacy of OncoPherese in each major cancer type? What drives recurrence and why does it sometimes not occur? For those patients in whom OncoPherese is ineffective, could adjunctive therapies improve outcomes? We are currently planning new, highly focused clinical trials to answer these and other questions.

Patient Management

In clinical medicine we want to destroy the cancer but also make the sick person healthy – two outcomes that donít always go together. Ideally weíd like to preserve the patientís quality of life during treatment too. For the patient to become well during treatment, the goal must be to obtain and maintain an immune-mediated tumor kill rate thatís faster than the tumor growth rate but slow enough to allow normal tissue to heal into the cavity left by the tumor. If a significant tumor dies too quickly, we may also be faced with tumor lysis syndrome (TLS), i.e. metabolic complications caused by the breakdown products of dying cancer cells, leading to acute renal failure, ARDS, and DIC. TLS is rare with conventional treatment, normally only occurring with lymphomas and leukemias. However, the tumor kill rate with OncoPherese is potentially so high that TLS can occur with any cancer type, unless the clinician carefully regulates the process. (Ref. J.B.R.M -1989)

Tumors in anatomic sites intolerant of tumor swelling require special attention, e.g. the CNS, where edema and hemorrhage are particular concerns. Vascular tumors that die too fast can hemorrhage. Transmural tumors in hollow viscera that necrose too fast can lead to perforation. In summary, great care and medical planning must be exercised, and complications anticipated, before effective immunologic treatments are applied. Sometimes surgical intervention or tumor de-bulking is necessary to maximize safety and optimize clinical outcomes.

Baseline Patient Evaluations

In order to assess patient progress throughout treatment, all incoming patients must undergo a series of blood tests and scans of their tumor regions. These tests should be performed by the patientís attending physician before referral; if necessary these tests can also be performed locally. A complete list of required tests is provided to patients and attending physicians upon acceptance of the patient for treatment.
We have an onsite OR for installation of a subclavian catheter for vascular access.
We have an onsite OR for installation of a subclavian catheter for vascular access.

Details of Clinical Treatment

A standard high flow dialysis catheter surgically placed in the subclavian vein is used for vascular access. The machine controller, much like a dialysis controller, pumps blood from the catheter through a plasma fractionation filter. Blood cells and macro-proteins are returned to the patientís body. The low molecular fraction of plasma is pumped over an affinity column containing covalently bound molecules with very high affinity for TNFR-1 and TNFR-2. The plasma fraction without inhibitors is returned to the patientís bloodstream. The level of these inhibitors is thus reduced in the body at a pace determined by plasma flow rate and duration, which are carefully regulated to induce an inflammatory response that destroys tumors faster than they form, but slowly enough to avoid inducing TLS. Clinical response correlates with the area under this curve, similar to an inverted pharmacokinetic curve. A schematic of the blood cycle is shown below.

Optimizing Clinical Responses & Outcomes

In order to obtain optimal clinical results, all aspects of healthy immune function must be addressed. Patients who have received significant prior myelosuppressive therapies respond less vigorously than treatment-naive patients. Likewise, tumors growing in areas of prior radiation therapy do not respond as well as tumors growing in normal tissue. It may be necessary to enhance patient immune function prior to OncoPherese treatment by raising the number of macrophages and lymphocytes with substances like GM-CSF, M-CSF, IL-7, etc.

Nutrition plays a vital role in this regard as well. Most people who live above 30 degrees north latitude become vitamin D deficient after October and begin to raise their levels as late as April. Vitamin D is essential for obtaining and maintaining a good immune response against cancers, viruses and fungi. Zinc is also an important co-factor in immune reactions, as are vitamin C, vitamin A and other micronutrients. Proper protein intake is also vital. Daily exercise, relaxation and proper sleep patterns are essential, too. The patient should be in proper endocrine balance. Thyroid function, adrenal cortical function and reproductive endocrinology must be managed effectively. Co-existing medical conditions must be addressed and corrected as much as possible to optimize immune strength.

All treatment rooms have views of the Alps; reducing stress is a priority.
All treatment rooms have views of the Alps; reducing stress is a priority.
Learning to deal effectively with daily stress and disease-related stress are also very important. Given the proven inverse correlation between stress and immune function, itís essential to provide a stress free clinical setting where the patient and his or her family are comfortable and relaxed. The patient visits each day with his or her doctors, who are also available on call day and night. Specially trained nurses are always at the patientís bedside during treatment. The medical setting is tranquil, with a panoramic view of the Alps. The patient has as much access to family and friends during treatment as desired; this too has been shown to reduce stress and promote recovery.

Assessing Patient Outcomes

OncoPherese presents novel considerations for post-therapeutic evaluation and follow-up, especially regarding scans. The cytokine-mediated inflammation elicited by OncoPherese produces transient inflammation and edema of the tumor. This is followed by hemorrhagic and coagulative tumor necrosis and finally a variable amount of fibrosis.

In most cases consulting radiologists have simply never seen such reactions and may be uncertain how to interpret what they are observing. The expected response to any effective pro-inflammatory tumor therapy is: short-term tumor inflammation and swelling followed by necrosis, loss of blood supply, tumor shrinkage, and fibrosis. Radiographically, this first produces increased tumor size – which can be misread as cancer progression – attended by decreasing density on non-contrasted CAT scan and increased SUV on PET. Later, one observes decreased density in Hounsfield Units and decreased contrast enhancement on CAT with decreased SUV on PET.

At the height of tumor inflammation the PET is positive not from tumor metabolism but rather from increased metabolism of inflammatory and other stromal cells, a sign of healing. This is followed by tumor shrinkage with failure of the mass to contrast enhance on contrasted CAT scan, but the lesion remains PET positive until healing is complete and the mass either resolves or becomes scar tissue.

Finally, the lesion assumes the density of scar tissue, reveals no contrast enhancement and becomes PET negative. In bone, lytic lesions will progress to sclerosis by CAT scan and plain X-ray. Such lesions will reveal PET scans that remain positive for many months possibly relating to increased metabolism of healing tissue and bone remodeling. Close coordination and ongoing discussion with the entire health care team is essential.

Patient Referral Process

To discuss referral of a patient for treatment,  please contact us.
This procedure is the most remarkable therapy I have ever seen. JAMES FRACKELTON, M.D.
In my medical opinion this treatment is a great advance in cancer therapeutics and should be made available on a wide basis and covered by insurance as soon as possible. ROBERT S. WATERS, M.D.
Each and every sarcoma patient deserves to have the same life-saving and limb preserving treatment that has been available to me. AM, PH.D.

Address:

International Immunology Foundation
Dr.-Siebert-Str. 5
83209 Prien
GERMANY

Weíre open from 9:00 a.m. to 5:00 p.m. Central European Time (Eastern Standard Time + 6 hours).

Phone:

From within Germany: +49-8051-909-300
From EU to Germany: +49-8051-909-300
From the U.S.: 011-49-8051-909-300

Fax:

From within Germany: +49-8051-909-301
From EU to Germany: +49-8051-909-301
From the U.S.: 011-49-8051-909-301