Case study Pancreatic cancer ALA-LDN.pdf

Integrative Cancer Therapies

8(4) 416–422

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DOI: 10.1177/1534735409352082

http://ict.sagepub.com

Revisiting the ALA/N ( a -Lipoic Acid/Low-

Dose Naltrexone) Protocol for People With

Metastatic and Nonmetastatic Pancreatic

Cancer: A Report of 3 New Cases

Burton M. Berkson, MD, MS, PhD, 1,2 Daniel M. Rubin, ND, FABNO, 3

and Arthur J. Berkson, MD 1

Abstract

The authors, in a previous article, described the long-term survival of a man with pancreatic cancer and metastases to the

liver, treated with intravenous alpha-lipoic acid and oral low-dose naltrexone (ALA/N) without any adverse effects. He is

alive and well 78 months after initial presentation. Three additional pancreatic cancer case studies are presented in this

article. At the time of this writing, the first patient, GB, is alive and well 39 months after presenting with adenocarcinoma of

the pancreas with metastases to the liver. The second patient, JK, who presented to the clinic with the same diagnosis was

treated with the ALA/N protocol and after 5 months of therapy, PET scan demonstrated no evidence of disease. The third

patient, RC, in addition to his pancreatic cancer with liver and retroperitoneal metastases, has a history of B-cell lymphoma

and prostate adenocarcinoma. After 4 months of the ALA/N protocol his PET scan demonstrated no signs of cancer. In this

article, the authors discuss the poly activity of ALA: as an agent that reduces oxidative stress, its ability to stabilize NF k B, its

ability to stimulate pro-oxidant apoptosic activity, and its discriminative ability to discourage the proliferation of malignant

cells. In addition, the ability of lowdose naltrexone to modulate an endogenous immune response is discussed. This is the

second article published on the ALA/N protocol and the authors believe the protocol warrants clinical trial.

Keywords

pancreatic cancer, naltrexone, low-dose naltrexone, LDN, ALA/N, a -lipoic acid, NF k B, nuclear factor k B, antioxidant,

gemcitabine

In March of 2006, the authors published a case study

describing the long-term survival of a man (JA) with a diag-

nosis of pancreatic adenocarcinoma with metastases to

his liver. 1 The diagnosis was made following biopsy at a

well-respected academic medical center. The gentleman

was originally treated with a single dose of a standard chemo-

therapy protocol, which failed, and he was told to go home

because his prognosis was hopeless.

Given this scenario, JA presented to the Integrative

Medical Center of New Mexico (IMCNM) and was seen in

consultation by the author (BMB). An integrative medical

program was then developed and prescribed for the patient.

The purpose of the program was 3-fold: (1) nutritional support

especially through specific antioxidant agents, (2) comfort

and palliation, and (3) immune system modulation via bio-

logical response modification. The major therapeutic agents

were intravenous (IV) a-lipoic acid (ALA), 300 to 600 mg,

2 days per week, and low-dose naltrexone (LDN), 4.5 mg

by mouth at bedtime. In addition, a triple antioxidant regi-

men consisting of oral ALA (600 mg per day), selenium

(200 mcg twice daily), and silymarin (300 mg 4 times a

day) was started. JA was also placed on a generally-

accepted-as healthy diet and lifestyle program.

After the first IV administration of the ALA, the patient

improved subjectively, prompting his voluntary comment,

“I have increased energy and a sense of well-being.” The

program was continued, and JA was extremely compliant.

After 3 months of a-lipoic acid and low-dose naltrexone

(ALA/N) therapy, JA returned to work.

Presently, 78 months following initial diagnosis, JA

appears and feels normal, and his CT scan displays attenua-

tion of the pancreatic tumors and the hepatic metastases.

1 The Integrative Medical Center of New Mexico, Las Cruces, NM, USA

2 New Mexico State University, Las Cruces, NM, USA

3 Southwest College of Naturopathic Physicians, Scottsdale, AZ, USA

Corresponding Author:

Daniel M. Rubin, Southwest College of Naturopathic Physicians, 7331

E Osborn Dr, Suite 330, Scottsdale, AZ, 85251, USA

Email:rubin@naturopathicspecialists.com

Berkson et al

417

In September of 2007, the same authors published a case

study of a 61-year-old man with non-Hodgkins lymphoma. 2

He refused standard therapy for religious reasons. On pre-

sentation, he had baseball-sized lymph nodes in his cervical

region and left groin as demonstrated by a PET scan; one

node contained biopsy-proven malignancy. After 6 months

of LDN therapy and only 2 weeks of IV ALA, a PET scan

demonstrated radiological remission; at the time of this

writing, he is still free of disease, 57 months after his diag-

nosis date.

The impact of our initial publication has caused several

other patients with pancreatic cancer to present to the

IMCNM requesting access to the ALA/N protocol. Some of

the more recent case studies are presented here.

Patient 1: GB

Mrs GB is a 74-year-old Californian woman who was diag-

nosed with gall-stone pancreatitis in 1996. She recovered

from her symptoms and was placed on maintenance ther-

apy. She had no further symptoms until presentation in

February of 2006, when during physical exam, a mass was

palpated in her epigastric region. A CT scan demonstrated

both a large mass in the head of her pancreas as well as

some hepatic parenchymal abnormalities, thought to repre-

sent metastatic deposits.

Soon thereafter, a fine-needle aspirate of the pancreas

demonstrated mucinous adenocarcinoma. Despite her physi-

cians’ urging to quickly begin an intensive chemotherapeutic

regimen, she declined because her religious beliefs pre-

cluded such a regimen. Subsequently, she was given a

prognosis of 3 to 6 months of life if she did not undergo the

proposed chemotherapy treatments.

Mrs GB’s friend had read about the ALA/N protocol

and suggested that she try the approach because she was

left with no other reasonable treatment opportunities. GB

came to the IMCNM in September 2006 with complaints

of only accelerating and profound chronic fatigue and

abdominal pain. On physical exam GB was rather thin and

pale, and a large mass was palpated in her upper abdomen.

Her Carcinoembryonic Antigen (CEA) was 6.7 and her

Carbohydrate Antigen 19-9 (CA 19-9) was 39.

A PET scan was then performed demonstrating a nodu-

lar focus of enhanced glucose metabolism in the right upper

quadrant of the abdomen with numerous hypermetabolic

areas in the liver (Figure 1). BMB did address the standard-

of-care approach for her disease, which the patient again

promptly declined. She was offered ALA/N, consented to

such, and the treatment was initiated.

As the treatment regimen continued, Mrs. GB was fol-

lowed carefully with periodic laboratory and physical

exams. She continued to improve in all parameters: sero-

logically, physically, and symptomatically. By February

2007 and again in March 2008, GB was declared to be in

Figure 1. Mrs GB September, 2006

radiological remission by PET surveillance (Figures 2 and

3). Serologically, her CEA and CA 19-9 both normalized

from 6.7 to 0.9 and from 39 to 18, respectively. At the time

of this writing, 39 months after her diagnosis, GB continues

with her treatment plan and has no signs of pancreatic

disease.

Patient 2: JK

JK is an 80-year-old woman with generalized atheroscle-

rotic vascular disease, diagnosed with adenocarcinoma of

the pancreas with possible metastatic disease of the liver in

September of 2005. Several months earlier, she began to

feel very tired, developed nausea, and started to lose

weight. Her general internist sent her to a gastroenterolo-

gist who ordered a CT scan and diagnosed a large lesion in

the head of the pancreas with other lesions in the liver

thought to be metastatic from the pancreas. A biopsy was

performed on the pancreatic tumor in December 2005, and

the pathology lab reported that it had missed the cancer.

Mrs JK had a further workup at an academic hospital, and

she was told that in spite of the negative biopsy, she had

pancreatic cancer and was given a grim prognosis. No fur-

ther treatment was suggested because of her advanced age.

JK’s family doctor, who was familiar with the innovative

oncology literature, suggested that she try a nonstandard

approach for her illness. She came to the IMCNM in Janu-

ary of 2006.

418

Integrative Cancer Therapies 8(4)

Figure 2. Mrs GB February, 2007

Figure 4. Mrs JK January 2006

were clear, and her heart had normal sounds and rhythm. A

large mass was easily palpated in her epigastric region.

January 2006 laboratory results showed leucopenia,

anemia, abnormal liver function, hyperglycemia, and a CA

19-9 of 353. A PET scan was performed and showed a large

mass in the head of the pancreas with possible metastatic

disease in the liver (Figure 4). The various standard treat-

ment options were explained; however, JK stated her desire

to delay such and in their place undergo the ALA/N

protocol.

As the treatment regimen was initiated and continued,

JK was followed carefully with periodic laboratory and

physical exams. She continued to put on weight and have

demonstrable serological improvement. In late June 2006

(5 months after her initial visit), a repeat PET scan was per-

formed, this time demonstrating no signs of pancreatic

adenocarcinoma (Figure 5). Mrs JK continued her treatment

program, and her health was maintained, symptom free.

In July of 2006, JK returned to her home in California

and stopped her ALA/N treatment regimen. By August

2006, she began to feel ill once more; a CT scan was per-

formed, which showed that the pancreatic adenocarcinoma

had indeed returned. She expired in November 2006, 14

months following initial diagnosis.

Figure 3. Mrs GB March 2008

JK had to be helped by her friend into the exam room

because she was too weak to walk and stand by herself. On

physical exam, she was found to be cachetic and pale. Her

skin was jaundiced and her sclerae were icteric. Her lungs

Patient 3: RC

RC, a 67-year-old male was conventionally treated for

prostate cancer with brachytherapy in 1996. In 1998, RC

Berkson et al

419

Figure 5. Mrs JK June 2006

Figure 6. Mr RC November 2006

developed abdominal pain and was diagnosed with a dif-

fuse large-cell lymphoma of B-cell origin. He was treated

with 6 cycles of CHOP (cyclophosphamide, doxorubicin,

vincristine, and prednisone) and radiation therapy.

RC developed painless jaundice in May of 2006 second-

ary to a distal, common bile duct obstruction. Exploratory

surgery was performed revealing a nonresectable pancre-

atic carcinoma. He underwent a choledochoduodenostomy

with gastrojejunostomy. The postoperative course became

complicated by an abdominal infection requiring drainage

and multiple courses of antibiotics. His external percutane-

ous biliary drain was never fully functional, resulting in

recurrent episodes of cholangitis.

RC went to a large medical center in San Diego for a

second opinion. A CT scan was performed, and it demon-

strated pancreatic cancer, liver metastases, and peritoneal

carcinomatosis. RC, too, was told that treatment would most

likely yield little therapeutic benefit and that no treatment

may be the favorable choice for him overall.

RC arrived at the IMCNM in November 2006. He was

emaciated and appeared in generally poor health. His CEA

was 5.8 and his CA 19-9 was 53.6. A PET scan was per-

formed, which showed hypermetabolic retroperitoneal

lesions, both to the left and right, indicative of a large pan-

creatic tumor with numerous metastases to the liver

(Figure 6). He was told that his disease process was well

advanced and that an ALA/N protocol would be devel-

oped that could possibly prolong his life. Opting for this,

RC was started on LDN 4.5 mg each night before bed

along with IV ALA.

RC continued the ALA/N until February 2007 when

another PET scan was performed. It showed a resolution

of the previously demonstrated pancreatic and retroperito-

neal lesions (Figure 7). RC was feeling so good that he was

scheduled to have an internalization of the percutaneous

biliary drain in March of 2007. He was examined by a med-

ical oncologist who commented that at this point, RC had

relatively little in the way of symptoms to palliate. The inter-

nalization of the biliary drain was performed, and on his

medical oncologist’s recommendation, he began a course of

gemcitabine. Just before starting chemotherapy, his CEA

had fallen from 53.6 to 2.6 and his CA 19-9 dropped from

146 to 113. His severe abdominal pain returned and because

of the need for narcotics, RC was taken off his LDN. He

soon developed septicemia, became unresponsive, and

expired in May 2007, 12 months after initial diagnosis.

Discussion

In general, patients with advanced carcinoma of the pancreas

have a very poor prognosis. The usual length of survival

following initial diagnosis ranges from 3 to 6 months. In

certain cases, surgical intervention is not an option, and

patients with advanced disease rarely live more than a few

weeks. The current view is that treatment should concentrate

on palliative management. 3

JA was a patient with biopsy-proven adenocarcinoma of

the pancreas with metastases to the liver that we started

420

Integrative Cancer Therapies 8(4)

the IMCNM with cachexia, jaundice, and abdominal pain.

He desired ALA/N protocol for his recent malignancy. He,

therefore, quickly weaned himself off of his narcotic and

subsequently began the LDN component. Soon after starting

the ALA/N protocol, RC began to feel better. He felt so good

that he went to surgery to internalize his percutaneous bili-

ary drain. Following surgery, he developed septicemia and

died in May of 2007, 12 months following the diagnosis of

pancreatic cancer.

The authors believe that the stability of the patient’s dis-

ease is attributable to the ALA/N protocol developed by

BMB. This is substantiated by our initial report in 2005, on

patient JA. 1

These cases all represent, at the least, a reinstatement of

a high quality of life for all patients who presented with

pancreatic cancer. Such an achievement places the ALA/N

protocol as a promising new treatment for people with this

disease.

a -Lipoic Acid

ALA is the first component in the protocol. It is a naturally

occurring cofactor that is active in an assortment of enzyme

complexes that control metabolism, including the conver-

sion of pyruvate to energy in the mitochondrion. ALA is

also a vigorous free radical scavenger that has demonstrated

the ability to reduce oxidative stress in a number of disor-

ders, including diabetes, liver disease, and cancer.

There have been a number of articles suggesting the use

of ALA in the treatment of various cancers. One article

reported that ALA induced hyperacetylation of histones.

Histones are proteins that are active in the proliferation of

many types of cancer cells. Inhibition of such can drive a cell

toward the apoptotic cascade. In this study, human cancer

cell lines became apoptotic after being exposed to ALA,

whereas the same treatment of normal cell lines did not induce

apoptosis. 4

Another mechanism whereby ALA may discourage the

growth of cancer cells is its ability to stabilize NF kB

(nuclear factor kB). 5 Under normal circumstances, NF kB

dimers reside in the cytoplasm. However, if activated, the

protein complex will translocate into the nucleus. On acti-

vation, it will launch the induction of more than 200 genes

demonstrated to suppress apoptosis (create increased sur-

vival) and induce cellular transformation, proliferation,

invasion, metastasis, chemoresistance, radio resistance,

and inflammation. 6 NF kB is a current and future target in

oncology treatment. Modern pharmacological treatment

has pointed toward NF kB, in that bortezomib, a novel

proteasome inhibitor, inhibits NF kB as one of its valued

demonstrations.

Additionally, Th1- and Th2-mediated immune system

cells react to pathogenic insults with various cell membra-

nous receptors. Many of these receptors start a cascade of

Figure 7. Mr RC PET scan February 2007

treating with the ALA/N protocol in November 2002. 1 Just

prior to this, and after 1 round of chemotherapy, JA was told

by a reputable academic medical center that there was little

hope for his survival. His progress is being followed by CT

scans and PET scans, and he has done very well on the

ALA/N protocol. Presently, 78 months after his initial pre-

sentation, he is back at work, free from symptoms, and

without progression of his disease.

GB was diagnosed with pancreatic cancer in February of

2006. She refused the standard therapies because of reli-

gious reasons. She was started on the ALA/N protocol and is

alive and free of signs and symptoms 39 months after initial

diagnosis.

JK was diagnosed with pancreatic carcinoma with metas-

tases to the liver in September of 2005. When she arrived at

the clinic in January of 2006, her quality of life was poor.

She was jaundiced and appeared cachectic. She was physi-

cally and emotionally exhausted, and complained of constant

abdominal pain and nausea. After a few weeks of ALA/N

therapy, her symptoms began to improve, and 9 months after

diagnosis and 6 months following the initiation of therapy,

her PET scan failed to demonstrate disease recurrence. During

this period of 6 months, she felt essentially normal, without

pain or nausea. After returning to her home state, her doctors

refused to continue the ALA/N protocol. She subsequently

had a brisk disease recurrence and succumbed to such in

November 2006, 14 months following initial diagnosis.

RC carried the diagnoses of 3 primary malignancies:

prostate adenocarcinoma, non-Hodgkin’s lymphoma, and

finally, pancreatic adenocarcinoma. He initially presented to

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