Ascorbic Acid Mixture
February 25, 2010 by admin
Filed under Immunotheraphy
Ascorbic Acid Mixture
An effective immune stimulant which is pharmacologically and therapeutically distinguishable from vitamin C
The history of vitamin C and its relationship to cancer treatment is of critical importance to understanding and appreciating the intriguing potential of this preparation. In the early 1970′s, Linus Pauling, Ph.D., a Nobel Prize winner in chemistry for his insights into the nature of the chemical bond, had a personal health problem. At the age of 68, Pauling, a tall thin individual, was experiencing a noticeable increase in the frequency and severity of viral illnesses.
At an American Chemical Society meeting, Pauling discussed this personal problem with Dr. Irving Stone, a fellow chemist who synthesized vitamin C. Dr. Stone’s advice to Pauling: take lots of vitamin C and see if you don’t get better. Pauling followed Stone’s advice and experienced a sufficiently unequivocal improvement in his health to strongly believe vitamin C could improve immune function. Pauling, after the fashion of the brilliant investigative mentality that he was, studied the world literature on how vitamin C might influence viral illnesses, concluding that it might be able to reduce cancer risk or treat existing cancer. A clinical test using patients was needed.
Pauling was able to develop a collaborative association with Scottish surgeon, Dr. Ewan Cameron. Dr. Cameron, a physician in rural Scotland at the Vale of Leven Hospital, Loch Lomondside, often diagnosed cancer in patients, but his next step in the socialized Scottish system was to schedule the patients for triage to the regional cancer hospital. But delays to acceptance were typically months, and patients historically were untreated during this protracted delay. Cameron decided to place diagnosed cancer patients on vitamin C rather than do nothing. Dr. Cameron is no longer living, but Dr. Smith had long discussions with him while he was still in Scotland and after he became Medical Director of the Linus Pauling Institute, Menlo Park, CA.
Dr. Pauling had suggested to Dr. Cameron that 10 grams of vitamin C daily was a good dose for an initial clinical trial. Dr. Cameron, however, found that patients balked at the 10 large tablets required and often failed to take the recommended dose due to the sheer bulk of medicine. Cameron went to his pharmacist for advice.
The pharmacist suggested a liquid preparation as possibly more acceptable. Conversion of the vitamin C, also known chemically as ascorbic acid, to a non-sour liquid was accomplished by adding baking soda. A form of sugar, sorbitol, was added as a preservative and as a sweetener. A flavor, cherry syrup, was added. Dr. Cameron’s patients in rural Scotland were sent back home with a several week supply of the ascorbic acid mixture which was typically dispensed in two brown one liter bottles. Refrigeration was recommended. The clinical trial was initiated.
Dr. Cameron reported dramatic improvements in median cancer survival. In addition to much longer survival, some patients experienced protracted remissions – there were survival plateaus observed in cancers which had been uniformly fatal. Cameron reported his results in the medical literature to a very skeptical and critical audience. Many physicians believed that an assertion that vitamins could treat cancer was ridiculous, and Cameron and Pauling were both subjected to harsh criticism.
A physician at the Mayo Clinic, Dr. Charles Moertel, then reported a clinical trial in cancer patients which was purportedly designed to confirm or refute Cameron’s claims of cancer patient benefit from vitamin C. Moertel took advanced cancer patients, many with advanced colon cancer who had failed chemotherapy, and subjected them to a randomized clinical trial. Patients either received one gram of vitamin C three times daily in the dry state, or patients received a look-alike placebo to use as a comparison. The results: no improvement in survival. Moertel wrote a prominent paper for the literature which asserted vitamin C was useless in advanced cancer patients.
But no one has ever reported an effort to repeat Dr. Cameron’s methodology. At the Mississipi Baptist Hospital in Jackson, Mississippi, in the late 1970′s and early 80′s Dr. Smith carefully prepared the vitamin C in the fashion described by the Vale of Levan pharmacist. The large median survival increase described by Cameron was not confirmed, but a significantly increased number of late survivors was clearly apparent. Vitamin C in irradiated cancer patients not receiving chemotherapy appeared to be of limited but clear benefit.
We now know now that vitamin C is chemically unstable in water-based (aqueous) solutions and progressively undergoes oxidative change. A theory integrating these facts was created, tested, and confirmed by clinical research at Mississippi Baptist Medical Center in Jackson, Mississippi by switching to tablet vitamin C and comparing the survival curves of ascorbic acid mixture and tablet vitamin C. Ascorbic acid mixture was superior.
Vitamin C is the most important antioxidant of the body, and is present in the aqueous phase of body tissues in relatively high concentration. Vitamin C is central in an elaborate physiological defense against dangerous chemical entities known as free radicals. Free radicals are produced normally by the controlled breakdown of food substances to create useful forms of stored energy and in many normal physiological processes at the molecular level. Remember, Linus Pauling’s Nobel Prize was for elucidation of the nature of the chemical bond. Pauling knew intuitively that free radicals must be produced by the molecular machinery of life, and that they must be controlled.
Vitamin C (ascorbate), when it stops a free radical, is oxidized to dehydroascorbate.
Dehydroascorbate, under normal circumstances, is converted back into ascorbate by an active enzymatic process (dehydroascorbate reductase) which is central to normal body preservation (homeostasis). Therefore, the presence of progressively increasing concentrations of vitamin C breakdown products simulates major infection or some other major deterioration of normal homeostatic reduction of oxidized vitamin C, which is the method by which vitamin C is restored after losing its ability to absorb a free radical.
Accordingly, it seems quite possible that a rise in oxidation by-products of vitamin C, such as would arise from the employment of ascorbic acid mixture as the pharmacological preparation used to ingest the vitamin C, may have signaled our ancestors for millennia that a serious attack on the vital integrity of the body was in force, and that an immune activation was the appropriate adaptive response.
Pauling, himself, seems to have suspected this hypothesis as representing an integrating theory. Constance Tsao, a researcher at the Pauling Institute, carried out a substantiating experiment under Pauling’s guidance. Four groups of identical mice were given human breast cancer. The diet of each group was different in that one group was given standard food, a second group was given large amounts of vitamin C in food, a third group was given large amounts of vitamin C in drinking water, and the fourth group received food with vitamin C and copper salts, copper salts being known to markedly accelerate the oxidation of vitamin C. The result: only the aqueous vitamin C was of significant benefit, and the mice receiving copper salt vitamin C lived longer than the rats receiving vitamin C in food, who were not benefitted at all.
In summary, the reports by Cameron may well have been valid, in spite of Moertel’s claims to the contrary. The key to the discrepency lies in the methodology.
But the interpretation of the study’s results may have been wrong. Cameron’s patients may well have benefitted more from the immune stimulating properties of ascorbate breakdown products than from the vitamin C itself.
Lung Cancer: Non Small-Cell Patient Joeseph Robinson
February 25, 2010 by admin
Filed under Immunotheraphy
Lung Cancer
Non Small-Cell Patient Joeseph Robinson
Joseph Robinson was 80 years old when he sought medical attention with a 23 pound weight loss, cough, marked weakness, and progressive right shoulder pain. Cell block from needle biopsy of the right upper lobe mass demonstrated adenocarcinoma, confirming the diagnosis of lung cancer which was felt to be present in both lungs. Due to age and sever disability, Mr. Robinson was not felt to be a chemotherapy candidate.
Mr. Robinson received 300 cGy in two weeks to both lung lesions and the right upper humerus which was quite sensitive to pressure clinically. His bone scan was normal.
Radiation alone in doses of this magnitude neither sterilizes sizable deposits of non small-cell lung cancer nor introduces a chance for cure in such patients. This is all the radiotherapy Mr. Robinson ever received.
Initial CT chest scan (see pre treatment below) confirmed a distinct soft tissue density mass in the right upper lobe. CT chest scan taken almost one year after diagnosis demonstrated only slight fibrotic traces in the right upper lobe. (see post treatment below)
Initial CT chest scan (below) also confirmed a well defined left lower soft tissue density mass. CT chest scan taken almost one year after diagnosis demonstrated complete disappearance in the left lower lobe mass. (see post treatment below)
Mr. Robinson’s regulatory surface markers demonstrated the expected reciprocal fall reflecting and confirming the dramatic rise of the natural killer and B-lymphocyte populations. By newer nomenclature OKT-3=CD3, OKT-11=CD2, OKT-4=CD4, OKT-8=CD8.
Mr. Robinson’s second subset analysis, using his first study as base line control, demonstrated an extreme interval rise in effector lymphocytes. Both natural killer markers, LEU-11 and LEU-7 were markedly increased well into the upper 1% of all studies at the University of Mississippi Medical Center Clinical Immunopathology Laboratory in Jackson, Mississippi. Activated T-lymphocytes, T-9, were in the upper 1%. B-lymphocytes, B4, were similarly increased.
By newer nomenclature LEU-11=CD16, and B4=CD19.
Chronic Lymphocytic Leukemia
February 25, 2010 by admin
Filed under Immunotheraphy
Breast Cancer
Case History
We include a report of this small group of patients here because we have observed apparent major responses in chronic lymphocytic leukemia (CLL) associated with and apparently caused by (the use of) BRM therapy. Over the last four years, we treated five patients who were not taking any conventional treatment. All patients are still alive, have excellent quality of life and have no complaints. We want to present here two case reports of patients who responded very well with normalization of elevated lymphocyte count, and a third case of significant lymphocyte drop followed by stabilization at the lower level.
Case 1
Caucasian male, 69-years-old, previous heavy smoker presented in 03/26/99 with abdominal pain, weakness, insomnia, depression, constipation and enlarged spleen caused by chronic lymphocytic leukemia. At the time the patient came to our Center, he was not receiving any treatment for his leukemia. CT scan of abdomen demonstrated splenomegaly – spleen measured 132 mm. WBC was 55.4 thousand/UL (nl 4.8-10 thousand); B2M (cancer biomarker) was 2.4 mg/L (nl 0-2).
Initial BRM therapy consisted of antioxidants (vitamin E, selenium, OPC, ascorbic acid mixture, vitamin A), gonadal hormone replacement (Premarin, Provera, testosterone gel, DHEA, pregnenolone), and other supplements which usually increase production of natural killer cells; i.e., melatonin, MacroForce, whey protein fraction (Immunocal), cat’s claw, multiple digestive enzymes, bromocriptine (Parlodel), omega 3-fatty acids, and MGN-3.
During subsequent visits, BRM’s were changed based on assessment of subjective and objective status.
The treatment and outcome of patient are summarized Table 1.
Table 1.
DATE WBC B2M Treatment
(4.8 -10) (0 -2)
03/16/98 42.0
03/26/98 55.4 Start BRM therapy
04/09/98 49.1
06/01/98 44.6 2.4
07/01/98 48.9
09/01/98 1.4
10/26/98 1.7
11/03/98 Stopped BRM’s “sick at stomach”
11/11/98 56.5 Restart BRM therapy
11/24/98 50.2
12/22/98 47.0
12/30/98 Start Parlodel 1.25 mg bid
01/14/99 35.8 2.8
02/15/99 Stopped Parlodel after mastodynia resolved
03/22/99 51.3 (Stopped Provera this day)
03/22/99 2.2
Re-start Parlodel
05/25/99 22.5 1.0
06/04/99 17.7
07/01/99 12.6 1.2
Case 2
Black female, age 55 years, presented 04/23/96 with aches in neck, back, legs, extreme weakness, hoarseness, loss of voice, anxiety, anorexia, constipation. Malignant lymphoma, follicular predominantly cleaved small cell type, was diagnosed in March 1993. After an initial two cycles of chemotherapy, patient believed herself unable to tolerate chemotherapy both emotionally and physically, and she absolutely refused chemotherapy because of its previous morbidity. Unfortunately, she was increasingly troubled by diffuse bony aches which were rather typical for bone marrow involvement. She decided to come in our Cancer Center for a trial on alternative medicine.
We told this patient that alternative medication was not likely to create a remission in her current condition which was that of rather advanced bone marrow progression, but that we could try to reduce the decline in immune resistance to cancer which occurs with aging with a bioresponse modifier regimen. BRM’s used included Premarin, Provera, methyl testosterone, bromocriptine (Parlodel), vitamin E, vitamin C, selenium, beta carotene, and cat’s claw.
The treatment and outcome of patient are summarized Table 2
Table 2.
Date WBC lymph % Treatment
(4.8 – 10) (15-41)
06/30/95 191,400 96 clorambucil and prednisone
07/03/95 131,700 96 repeat chemo; no further chemotherapy
07/06/95 78.1 89
08/21/95 4.1 33
09/28/95 3.6 44
10/24/95 9.2 63.9
12/14/95 32.7 83.7
12/27/95 40.6 83.7
01/22/96 61.4 90
03/21/96 61.3
04/23/96 39.3 87.4 start BRM regimen
05/16/96 28.3
06/10/96 27.5 81.4
06/17/96 21.1
08/08/96 16.6 71.3
08/12/96 14.9 77
10/07/96 6.2 55
12/02/96 4.5 43
03/03/97 4.5 38
04/28/97 4.8 37.6
Author’s Comment: This patient’s greatly elevated WBC completely normalized with substantial improvement in quality of life. Virtually all chemotherapy for this condition involves agents which result in increased genetic instability. The natural history of CLL is several years of stable count on chemotherapy followed by a fulminant progression due to dedifferentiation of the malignancy to a more malignant form. Any modality capable of inducing normalization of counts which is non toxic and which does not involve agents which destabilize the genome is almost certainly capable of extending overall survival. The question arises from this case: when if ever should BRM by (be) primary standard of care followed by conventional chemotherapy for BRM failure?
Case 3
Caucasian female, age 71 years, presented 07/05/96 with known CLL since 1981, malaise, and a rising white count. Patient complained of a very low energy level and psychological depression. For the last sixteen years she had done very well. She continued to take daily Cytoxan 50 mg, one tablet five times a week. She had not had any systemic symptoms during this period. Her white count, however, had risen to 31,500 and her quality of life had dropped markedly. CT scan of the chest and abdomen demonstrated numerous axillary nodes present greater on the right than on the left. Most of these measured less than a cm., with 1.5 cm. being the maximum diameter. The spleen was enlarged.
We suggested BRM’s consisting of ascorbic acid mixture, vitamin E, selenium, cimetidine, Premarin, natural progesterone, and bromocriptine. She tolerated BRM therapy reasonably well except for nausea and relative intolerance to bromocriptine. Since BRM’s, self-perceived health was clearly better. Energy improved. Mood was generally improved. Depression was lessened. She stopped taking ascorbic acid mixture, attributing sore mouth to this agent even after reducing her dose. WBC dropped to 24120 during first month. During follow ups we changed BRM’s according to her subjective and objective data.
Patient takes cat’s claw, OPC’s, Immunocal, DHEA, pregnenolone, multiple enzymes, MacroForce, MSM, HGH, and hydrazine sulfate.
The treatment and outcome of patient are summarized Table 3
Table 3.
Date WBC % lymphs Treatment
04/05/96 18.85 67.7
07/05/96 32.1 start BRM
07/09/96 31.5 85.0
08/28/96 24.12
11/04/96 21.3 80.4
12/04/96 17.9 80.2
01/14/97 start HGH 12 days
01/21/97 22.1 80.1
01/21/97 stop HGH (WBC elevation)
02/11/97 19.32
02/26/97 23.69 88.0
05/12/97 19.2 80.3
05/13/97 start hydrazine sulfate
06/24/97 24.8 85.2
06/24/97 stop hydrazine sulfate (WBC elevation)
08/25/97 22.39 73.7
09/09/97 24.1 84.6
10/27/97 22.9 82.9
01/06/98 24.6 83.3
02/25/98 22.73 7 2.0
06/05/98 27.5
08/26/98 28.44 74.8
12/01/98 30.3
02/17/99 27.42
06/22/99 23.4 84.4
Author’s Comment: Patient’s disease, as assessed by lymphocyte count, initially declined and then remained very stable with white count running 20,000 to 24,000. Chest X-ray 02/24/99 was normal. Quality of life is good. As natural history of disease is typically a gradual rise in WBC, a positive response from BRM appears to be present.
Breast Cancer
February 25, 2010 by admin
Filed under Breast Cancer, Immunotheraphy
Breast Cancer
Case History
My diagnosis of breast cancer came as a complete shock because I had a clear mammogram. But my type of cancer, lobular carcinoma, doesn’t show up on mammograms. Mine was extensive, with 20 of 24 nodes involved. I underwent a modified radical mastectomy followed by both radiation therapy and intensive chemotherapy. After a follow-up visit, I was told that the cancer was still there. Discouraged and feeling physically exhausted, I decided I couldn’t endure another round of chemotherapy.
I had read about immune therapy being used in conjunction with radiation therapy at the Cancer Center in Greenwood even before my physician recommended that I go there. He knew that Dr. Smith had seen some promising results with his methods that stimulate the immune system’s response to cancer and are believed to increase the tolerance and effectiveness of traditional therapies.
My husband and I have two daughters — one in Texas and one in upstate New York — whom we enjoy visiting as often as possible. Our daughter in New York is a nurse, and she thinks it’s great that I’m able to receive this type therapy here. She knows that immunotherapy is being researched and used in some of the largest cancer treatment facilities in the country.
I appreciate the fact that Dr. Smith allows me to be part of the team. He explains the possible benefits and risks at every step and lets me decide what I’m most comfortable with. After eight months, the markers are good*, my disease is stable, and I’m feeling better every day. I only wish everyone could have access to this method of cancer treatment that has given me back both my energy and my hope.
*Helen’s treatment recently caused her natural killer lymphocytes to reach 61% (normal range 3 – 15%).
Case History
Caucasian female, age 62, underwent radical mastectomy and axillary dissection for lobular carcinoma 5/3/96, with 20 nodes positive. She received postoperative cytoxan, methotrexate / fluorouracil for one cycle, doxarubacin for four cycles, and taxol for four cycles. She was referred for regional radiotherapy after the chemotherapy and seven months after surgery. Serum BR27.29 documented an interval rise from 56 to 152 during the chemotherapy. The patient was despondent and weak from side effects of intensive chemotherapy.
During initial radiotherapy, BRM therapy was begun with natural vitamin E 400 IU three times daily, selenium 200 mcg twice daily, vitamin C 5 g once daily, oligomeric proanthocyanidins 200 mg daily, human growth hormone (HGH) one unit SC twice daily, melatonin 50 mg at hs, and IL-2 5.5 IU / day. GM-CSF 250 mcg was added at bedtime.
Over the next three months the NK% reached 61. BR27.29 remained low for two years during which time there were nine NK% determinations more than 50, and many more than 40.
Authors’ comments: There is lay disinformation that previous chemotherapy precludes successful complimentary medicine / biological approaches. We propose many if not most anecdotal remissions are immunologically driven and would be evidenced by increased NK% if tested during the remission process. The interval NK% increase and absolute NK% elevation observed in this case confirmed alteration of immune system activity, and the ability of IL-2 based regimen in this case to stimulate NK% clearly was not incapacitated by the previous chemotherapy. In this patient’s case, where further cytotoxic chemotherapy was very unlikely to beneficially damage tumor, and where patient’s physiologic reserve was seriously compromised, immunotherapy proved a “way out of the trap”.
Lung Cancer: Bronchoalveolar Carcinoma
February 25, 2010 by admin
Filed under Immunotheraphy
Lung Cancer
Bronchoalveolar Carcinoma
A 56 year old caucasian male was taken to the emergency room with acute hypertension in May,1997. Chest X-ray revealed opacity in the right upper lung. CT chest scan revealed mass in the right apical region with some abutment to the pleural margin. Needle biopsy revealed bronchioloalveolar carcinoma.
The final pathology report from thoracotomy 5/25/97 describes bronchioloalveolar carcinoma of the right upper lobe tumor extending to, but not through, the pleural surface. There was tumor present in peribronchial vessels and paravascular tissue at the surgical margin. There was involvement of lymphatic vessels by tumor and microscopic tumor in four lymph nodes examined. Patient received adjuvant radiotherapy after surgery, but he developed a regional relapse in the neck and chest wall. Patient initiated BRM’s including IL-2, 5.5 million IU daily. Initial NK% 07/21/97 was 11 and serum IAP was 650 (nl<600) . During immunotherapy NK% level fluctuated, but over months remained at 44 to 62%, during which time IAP dropped from 830 to 330. In January, 1998, NK% dropped to 3 and IAP increased to 760. Multiple severe painful metastases to the chest wall and right supraclavicular area were diagnosed. Intralesional injection with absolute alcohol relieved his symptoms and intralesional IL-2 was associated with an arrest of local cancer growth.
Patient started taking Taxol and carboplatin. In present time patient continues to take chemotherapy and BRM’s and has no symptoms of cancer recurrence.
Authors’ comments: Bronchoalveolar cancer is often refractory to systemic management. This patient’s local disappearance of gross clinical cancer after IL2 injections in a blood state of marked IAP elevation heightens the perception of anomaly.
Lung Cancer: Squamous Cell with Bilateral Lung Masses
February 25, 2010 by admin
Filed under Immunotheraphy
Lung Cancer
Squamous Cell with Bilateral Lung Masses
Caucasian male, age 52, presented with masses in both pulmonary apices. Right upper lobectomy 2/13/97 removed a 2.8 cm squamous cell carcinoma with hilar adenopathy. The left nodule, right hilum and mediastinum received radiotherapy to 5220. BRM was begun during radiotherapy as with Case 4.
During the five months immediately after surgery, LASA-P rose from 24 to 30. IL-2/melatonin using the Lissoni schedule was added to the BRM regimen. After another five months had elapsed, NK% had climbed from 11 to 45. A further nine months later, LASA-P had climbed to 49 and NK% to 65. BRM’s included IL-2 3.6 mln IU daily, GM-CSF 250 mcg every other day, vitamin E 1000 IU once a day, testosterone patches 5 mg daily, ascorbic acid mixture tbsp (2.5 g ascorbate) twice daily, bromocriptine 1.25 mg twice daily, cimetidine 300 mg four times daily, aspirin 5 grains daily, beta 1,3 D-glucan one daily, omega-3 fatty acids 1000 mg daily, equine conjugated estrogen in two week cycles followed by medroxyprogesterone acetate 10 days then off 6 days in cycles, saw palmetto 160 mg twice daily, oligomeric proanthocyanidins 150 mg three times daily, DHEA 50 mg twice daily, melatonin 50 mg daily.
After discussion of his options, patient deferred chemotherapy, and 27 months after presenting with suspected bilateral disease, and in spite of a tumor marker peak 2.5 times the upper limit of normal, (his LASA-P normalized recently) he remains very active and fully employed in farming related businesses. Morbidity of BRM therapy is attributable to injection site indurations from the IL-2 and IL-2 related fevers / malaise of tolerable degree.
Authors’ comments: Bilateral lung masses and surgically documented hilar adenopathy greatly increased the risk of postoperative systemic failure. The postoperative interval rise to twice normal and the absolute elevation of LASA-P at 53.3 (nl 10-24) suggest progressive systemic disease. Continued good quality survival in the face of elevated non-progressive LASA-P and elevated NK% suggests remission, not cure, and further suggests a causal relationship of the elevated NK% to the remission status.
Lung Cancer: Squamous Cell with Pleural Effusion and Unresectable Mediastinal Nodes
February 25, 2010 by admin
Filed under Immunotheraphy
Lung Cancer
Squamous Cell with Pleural Effusion and Unresectable Mediastinal Nodes
Caucasian male, age 54, presented 08/04/95 with five cm perihilar squamous cell lung cancer. At upper lobectomy, tumor extended to the mainstem bronchial resection margin, extended to pleura, involved two of ten nodes, and extended as bulky unresectable nodes into the mediastinum. Patient was treated with postoperative radiotherapy of 6840 cGy to bulky adenopathy with concurrent 5-FU infusion and cisplatin. During radiotherapy, BRM with cyclical equine conjugated estrogen and medroxyprogesterone acetate was begun as described in Case 3. Vitamin E 400 IU tid and cimetidine 300 mg qid were also begun.
Three months later the patient reported refractory cough and shortness of breath. CT scan reported bulky residual adenopathy. LASA-P serologic marker was 20.3 (nl < 20). At this time the first of four irridium-192 endobronchial implants were performed for symptomatic disease compressing bronchus. Thoracentesis of a large symptomatic effusion was also performed. Eight months later the fourth endobronchial implant delivering 1000 cGy at 1/2 cm was delivered with repeat thoracentesis of a symptomatic pleural effusion.
Six months later (4/2/97) IL-2 immunotherapy was begun with 5.5 million units nightly plus melatonin 50 mg at bed time and DHEA 50 mg twice a day. NK% at this time was 16. By six months later, NK % had risen to 55. There were subsequent ten NK determinations more than 40.
On 11/3/98, the patient’s tolerance to IL-2 had deteriorated, and he elected to discontinue IL-2. In only two months after the first thoracentesis for symptomatic effusion, the LASA -P marker was observed to have risen during two months from 16.4 to 29.4. During this same two months, NK% had dropped from 44 to 22, and NK function from 508 to 51 (nl 20-250). Restarting IL-2 and testosterone injection 200 mg in oil was associated with a drop of LASA-P from 29.4 to 14.6 and rise in NK% from 22 to 46 and NK function – to 339.
Three and one half years after thoracotomy for unresectable tumor, and three years after thoracentesis for symptomatic effusion, and after peaks of LASA-P well above normal were observed, the patient leads a vigorous lifestyle doing some work as a mason and maintaining a Karnovsky score of 100.
Authors’ comments: The persistent elevation of LASA-P supports the scanographic and endoscopic diagnoses of failed regional control necessitating multiple endobronchial implants. Patient’s persistent clinical remission during well documented elevation of NK% suggests active sinecommitant immunity.
Lung Cancer: Adenocarcinoma of the Lung with Metastasis of Neck, Ribs, and Humerus
February 25, 2010 by admin
Filed under Immunotheraphy
Lung Cancer
Adenocarcinoma of the Lung with Metastasis of Neck, Ribs, and Humerus
Caucasian female age 88 years, presented 12/12/84 with a 4 cm right upper lobe mass. Needle biopsy was interpreted as poorly differentiated adenocarcinoma. Radical radiotherapy (7000 cGy) was delivered to the primary cancer. Two months later radiotherapy was delivered to apparent painful metastatic sites in the right proximal humerus and left rib cage and to a diffuse mass expanding the right neck. Two months later the same areas were retreated. Four months later the right neck was treated for the third time. Due to the patient’s age and early senility, chemotherapy was never recommended.
Concurrent with the initial radiotherapy, vitamin E 1000 IU, bromocriptine 1.25 IU twice daily, and medroxyprogesterone acetate10 mg twice daily were begun. Use of these medications by the patient was sustained after radiotherapy, except for the vitamin E.
After an unanticipated remission in new bone or soft tissue manifestations lasting more than two years, a lymphocyte subset analysis was obtained. This study revealed the NK surface markers, Leu 7 to be 60.2% and Leu 11 = 69.6%, by far the highest level ever seen before or after at the Clinical Immunopathology Laboratory at the University of Mississippi Medical Center. Death of senile brain disease, sepsis, and dehydration occurred one year after documentation during remission of extraordinary NK%.
Until her death from pneumonia 3 years after radiotherapy, the patient manifested a large diffuse soft tissue mass in the base of the right neck over the previously irradiated apparent supraclavicular recurrence. She continued cimetidine 300 mg four times daily and medroxyprogesterone acetate 10 mg twice daily and did not experience a second relapse. No serologic markers were employed.
Authors comments: Arrest of metastatic progression of disseminated lung cancer with evidence of extraordinary NK% elevation to more than four times the upper limit of normal supports the hypothesis of efficacious NK based sinecommitant immunity.
Lung Cancer: Adenocarcinoma of the Lung with Multiple Brain Metastases
February 25, 2010 by admin
Filed under Immunotheraphy
Lung Cancer
Adenocarcinoma of the Lung with Multiple Brain Metastases
Metastatic spread to brain is a major problem in patients with cancer of lung origin. Primary tumor resection is contraindicated in patients with carcinoma of the lung who present with concurrent cerebral metastases, as there is virtually no chance for cure in such a setting (1-3). Opinions concerning optimal therapy vary widely.
Literature reports of fully active survivorship of more than two years in non-small cell lung cancer (NSCLC) with unresected brain metastasis have not been found. While some authors have reported patients who were alive, well, and working after resection of both primary and a solitary brain metastasis (4,5), multiple brain metastases at presentation is widely felt to be a contraindication to therapy.
Protracted cancer survival with immunotherapy was interpreted as establishing a “proof of principle” (6,7). The applicability of such methodology to lung cancer is not established by randomized prospective trial.
CASE REPORT
A 47-year-old male with a one week history of right sided weakness, gait instability, and headache was hospitalized after a grand mal seizure caused post ictal right hemiplegia and aphasia. One week before presentation he was treated for deep venous thrombosis.
CT scan demonstrated multiple brain lesions (picture below). Chest CT scan revealed a small peripheral lung mass and multiple cavitary mediastinal nodes none of which exceeded 2 cm in diameter. Nodal biopsy at mediastinoscopy confirmed adenocarcinoma. Initial CEA was 111.2 ng / mL (nl < 3.0).
Unusual aspects of this patient’s presentation favoring BRM intervention included small volume primary tumor, small volume regional adenopathy, and asymptomatic locoregional tumor. Aside from the central nervous system, there were no systemic manifestations of metastatic spread. The patient was young and physically active. To assess efficacy of BRM intervention, CEA was a potentially useful clinical marker.
Initial brain radiotherapy with 180 cGy x 25 = 4500 cGy in five weeks was intended to cause bulk reduction in the brain. As post radiotherapy immunotherapy with GH secretagogue methodology was planned, the hypophysis and immediately overlying hypothalamus was excluded from the bilateral treatment fields.
The mediastinum was initially left unirradiated because it was hoped that BRM therapy might restore growth hormone (GH) secretion and result in improved thymus gland function. Initial BRM therapy begun during radiotherapy consisted of equine conjugated estrogen 1.25 mg twice daily, methyl testosterone 10 mg twice daily, ascorbate 1000 mg daily, alpha-tocopherol acetate 400 IU three times daily, cimetidine 400 mg three times daily, and a troche containing coenzyme Q-10 200 mg / ergaloid mesylates 10 mg daily.
During the therapy, neurological signs and symptoms eventually returned to normal. After radiotherapy BRM was continued by the addition of medroxyprogesterone acetate 10 mg twice daily after 14 day cycles of equine conjugated estrogen, bromocriptine1.25 mg twice daily, tetraiodothyronine 100 mcg daily, coumadin 2.5 mg daily, melatonin 50 mg daily, and interleukin-2 (IL-2), 5.5 million units subcutaneously at bed time.
IL-2 was associated with a progressive decline in CEA ending five weeks later in Jan. 1996, when a small rise led to the conclusion that the mediastinal tumor was probably progressing. Irradiation of the primary tumor and node containing mediastinum with a total dose of 180 cGy x 28 = 5040 cGy was carried out. After chest radiotherapy was completed, IL-2 was restarted, and another CEA decline was documented for five months during continued IL-2 therapy. A very gradual rise was noted.
Natural killer cell and CEA response to Immunotherapy
Treatment caused 13 interval reductions in CEA. The first started after brain radiotherapy. The second began at the time of chest radiotherapy. Over these two intervals, 5,5 million units of IL-2 was injected nightly. A fall in CEA from 111.2 to 5.7 (fig. 1) was observed. Natural killer cells (NKH-1) during this period rose from 14% (nl 3-15%) on Dec. 14, 1994 to 62% on 5/1/95.
After serial CEA determinations showed declines had ceased, the patient had become weak and despondent from the long course of immunotherapy, and he elected to stop the IL-2.
Note the rapid subsequent rise in CEA from 5.9 to 20.7 over just four weeks. Graph segments showing CEA decline usually occurred during eight day cycles of IL-2. It was noted that the end cycle CEA levels (nadirs) were gradually rising, and the magnitude of the CEA drop associated with the IL-2 cycles was decreasing. Development of tumor resistant to IL-2 was feared. Granulocyte-monocyte colony stimulating factor (GM-CSF) injections were added to the IL-2 injections at this time. Cycles of IL-2 / GM-CSF were begun on 7/1/96. Both GM-CSF and IL-2 were injected in the same place and at bedtime. The magnitude of CEA decline associated with the two combination IL-2 / GM-CSF cycles was relatively large compared to the two which proceeded them. A CEA decline from 20.0 to 12.1 was noted during the cycle of IL-2 / GM-CSF.
The patient noted clinically positive one cm nodes in the lower neck, progressive cough and anorexia. Chest CT demonstrated a right hilar mass and growth at the original site of the primary tumor. Nodules noted in the lower half of the neck on both sides were irradiated ending 9/20/96.
Patient continued to take courses of IL-2 therapy, and HGH and DHEA were added to lessen side effects. These agents resulted in a qualitative change in patient tolerance, the patient feeling robust and vigorous throughout the last cycle of treatment. The improved tolerance seemed attributable to the concurrent use of HGH.
Follow up CT scan of the brain 04/02/97 revealed a very much reduced density at the site of the previous large mass, and no evidence of recurrence (picture below). There has never been any evidence of central nervous system recurrence.
DISCUSSION
Radiotherapy for brain metastases is widely accepted, but survival is short. Recurrences of NSCLC in the brain, the “sanctuary effect”, have been common in systemically treated lung cancer patients, and, adenocarcinoma of the lung, in particular, seems to exhibit a predisposition for CNS relapse in patients previously treated with chemotherapy (8). We did not choose chemotherapy as initial therapy.
Perceiving CEA elevation as a clinical tool with which to monitor success or failure of immunotherapy, we decided to explore the use of combination BRM. We have had a long interest in BRM therapy of lung adenocarcinoma (9-11).
Proof for BRM efficacy in metastatic cancer arises from use of IL-2 for renal cell carcinoma and melanoma (12-14). Recent evidence suggest low dose subcutaneous IL-2 is efficacious in carcinomas (15-16). This case suggests IL-2 may be combined with other agents resulting in increased efficacy, and with a combination of low dose HGH and IL-2 deserving special attention.
Both the lymphocyte lineage and the monocyte / macrophage lineage arise from the same primitive stem cell. IL-2 is a growth factor exclusively stimulating the entire lymphocyte lineage, including B cells and NK, and lymphokine activated killer (LAK) cells (17). GM-CSF stimulates the macrophages, also capable of contact cytotoxicity. There is cooperation or “crosstalk” between these two systems in cancer recognition and contact cytotoxicity; GM-CSF has been shown to enhance the cytotoxicity of IL-2 stimulated LAK cells in the peripheral blood (18). If both lineages are influenced by age related loss, restoring one lineage without restoring the other could greatly limit overall efficacy.
We studied the effect of IL-2 and GM-CSF administered subcutaneously. We noted that the two agents markedly increased the IL-2 injection site indurations if the two agents were injected at the same site. We hypothesized that monoclonal proliferation of immunocytes taking place in the injection site indurations, which reached 6 – 8 cm across, could give rise to circulating systemically active killer cells.
This IL-2 / GM-CSF combination caused more side effects. The confluent injection site induration was painful, and fever and other flu-like side effects of the treatment were pronounced.
Melatonin as a potentiator of IL-2 efficacy has been reviewed by Rozencwaig (19). Many studies support the concept that antioxidant vitamins have immune stimulating effects (20-23). Dietary intake vitamins C and E may not only play a role in defense against oxidative damage, but may increase the intensity of immune resistance to cancer once cancer is present. Added dietary selenium induces the endogenous production of glutathione peroxidase, a powerful selenoenzyme antioxidant (24-25).
Sinecommitant immunity is recognizable in this case by the ability of the immune system to repeatedly cause decline in CEA, such decline being generally accepted as an accurate indication for tumor response. The cancer condition is a dynamic state, much like warring forces across a battle front. In this case the forces of neoplasia and the forces of defense were relatively equally balanced for many months.
Recombinant proteins, including HGH, GM-CSF, beta interferon, and IL-2, are sufficiently new to the arsenal of the oncologists, and the clinical efficacy of combination treatments is relatively unexplored. In a single protracted case history we observe several combinations which appear to cause not only an objective anticancer effect but a treatment tolerable by quality of life standards. In this case we maintained a regimen of oral BRM’s essentially unchanged throughout treatment, and CEA variations were caused at the margin by recombinant protein injections.
In conclusion, multimodality treatment with radiotherapy and BRM including IL-2 and GM-CSF may was consistent with an excellent quality of life, allowing continued gainful employment for 30 months. This unusual case suggests similar treatment and monitoring methodology may have a wider application.
Lung Cancer: Non Small-Cell Patient Joe Woods
February 25, 2010 by admin
Filed under Immunotheraphy
Lung Cancer
Non Small-Cell Patient Joe Woods
Joe Woods was a 66 year old chronic smoker when he sought medical attention for progressive right upper chest pain. Joe had not lost weight, but for the last few years he had been troubled by increasing weakness and loss of stamina. Joe was also troubled by marked shortness of breath with mild exertion, a condition attributed to “asthma” and treated with a Primatine inhaler.
Initial chest scan of 1/13/88 taken before treatment shows a 4 cm mass broadly adherent to the pleural surface wit prominent adjacent pleural thickening. Mr. Woods’ sputum contained abnormally keratinized apithelial cells, having irregular or deeply hyperchromatic nuclei, which were interpreted as cytologicaly diagnostic for squamous cell carcinoma. Subsequent to cytologic diagnosis, further staging included CT brain scan, CT abdominal scan, bone scan, and CT chest scan — all of which failed to reveal spread beyond the right upper chest.
Pulmonary function studies revealed profound obstructive disease with FEV1 of 1.11 liters (43% of predicted), and Joe was judged to be both medically and surgically inoperable. Simulation film taken 1/29/88 in preparation for combined concurrent irradiation and chemotherapy reveals the large right upper lobe lung mass which seems to have grown since the CT chest scan two weeks earlier.