Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy (Case report)
Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy
Akbar Khan, Doug Andrews, Anneke C Blackburn
Akbar Khan, Douglas Andrews, Medicor Cancer Centres Inc., Toronto, ON M2N 6N4, Canada
Anneke C Blackburn, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
Author contributions: Khan A treated the patient and wrote most of the case report; Andrews D treated the patient, designed
the natural therapy protocols, and co-wrote the case report; Blackburn AC performed in vitro and in vivo work demonstrating
DCA’s effects as a cytostatic agent, and wrote the parts of the case report dealing with the in vitro and in vivo DCA research.
Institutional review board statement: Not applicable.
Informed consent statement: The patient described in this manuscript has given consent to publish her case anonymously.
Conflict-of-interest statement: One of the authors (Khan) administers dichloroacetate therapy for cancer patients through
Medicor Cancer Centres at a cost, and without profit. The clinic is owned by a family member of this author. The other authors have
nothing to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external
reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms,
provided the original work is properly cited and the use is non-commercial.
Manuscript source: Invited manuscript
Correspondence to: Akbar Khan, MD, Medical Director,
Medicor Cancer Centres Inc., 4576 Yonge St., Suite 301, Toronto,
ON M2N 6N4, Canada. firstname.lastname@example.org
Received: April 30, 2016
Peer-review started: May 3, 2016
First decision: June 17, 2016
Revised: July 23, 2016
Accepted: August 6, 2016
Article in press: August 8, 2016
Published online: October 16, 2016
Oral dichloroacetate sodium (DCA) has been investi-gated as a novel metabolic therapy for various cancers
since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain
cancer cells. Response to therapy in human studies is measured by standard response evaluation criteria
for solid tumours definitions, which define “response” by the degree of tumour reduction, or tumour disap-
pearance on imaging.
However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo , without
causing apoptosis (programmed cell death). A case is presented in which oral DCA therapy resulted in tum our
stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity.
Since the natural history of stage 4 colon cancer consists of steady progression leading to disability and death,
this case highlights a novel use of DCA as a cytostatic agent with a potential to maintain long-term stability of
Key words: Dichloroacetate; Cancer; Colon; Colorectal; Cytostatic; Stabilization; Growth inhibition; Intravenous
© The Author(s) 2016. Published by Baishideng Publishing
Group Inc. All rights reserved.
Core tip: Oral dichloroacetate sodium (DCA) has been investigated as a novel metabolic therapy for various cancers.
Response to therapy in human studies is measured by standard response evaluation criteria for solid tumours definitions,
which define “response” by the degree of tumour reduction, or tumour disappearance on imaging.
However, DCA can also act as a cytostatic agent, without causing apoptosis (programmed cell death).
A case is presented in which oral DCA therapy resulted in tumour stabilization of stage 4 colon cancer
in a 57 years old female for a period of nearly 4 years, with no serious toxicity.
Khan A, Andrews D, Blackburn AC. Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy.
World J Clin Cases 2016; 4(10): 336-343
Available from: URL: http://www.wjgnet.com/2307-8960/full/v4/i10/336.htm
The drug sodium dichloroacetate (DCA) has been investigated as a novel metabolic therapy for various
cancers since 2007 when Bonnet et al published a combined in vitro/in vivo rat study demonstrating the
efficacy of DCA in treating human lung, breast and brain cancers by inhibition of mitochondrial pyruvate
dehydrogenase kinase. Stacpoole et al[2-4] had pre-viously published multiple studies involving DCA for
the treatment of congenital lactic acidosis, which is composed of a collection of inherited mitochondrial
These studies established the safety profile of oral DCA in humans. DCA was discovered to be a safe drug with no
cardiac, pulmonary, renal or bone marrow toxicity. The most serious common side effect consists of peripheral neuropathy,
which is reversible. Delirium has been reported, and is reversible after discontinuation of DCA. Asymptomatic and
reversible liver enzyme elevation has been reported in a small percentage of patients.
The prior work in congenital lactic acidosis has enabled the rapid progression of DCA into the cancer clinic. Four reports
have now been published of cancer clinical trials using DCA, indicating a growing recognition of the potential usefulness
of DCA[8-11]. However, these trials treating late stage patients, have only been able to report on treatment for relatively short time periods.
In the initial 2007 paper by Bonnet et al, it was reported that DCA reduced mitochondrial membrane potential resulting in selective
apoptosis in cancer cells. The mechanism identified was inhibition of aerobic glycolysis (the Warburg effect) and activation of
mitochondrial potassium ion channels.
Further investigation of DCA confirmed anti-cancer activity in several cancer types including colon, prostate, ovarian,
neuroblastoma, lung carcinoid, cervical, endometrial, cholangiocarcinoma, sarcoma and T-cell lymphoma.
Other antineoplastic actions of DCA have also been suggested. These include angiogenesis blockade, changes in expression of
HIF1-α, alteration of pH regulators V-ATPase and MCT1, and other cell survival regulators such as PUMA, GLUT1, Bcl2 and p53.
However, in the quest for cytotoxic activity, many in vitro reports use concentrations of DCA that are unlikely to be achieved clinically.
Some studies have used restricted concentrations and found DCA to be cytostatic rather than cytotoxic, but able to enhance apoptosis with
other agents[26-28]. In the report of successful in vivo DCA treatment of breast cancer, Sun et al found DCA to be cytostatic, inhibiting
proliferation without increasing apoptosis. DCA was able to significantly reduce metastatic burden in the lungs of rats in a highly
metastatic in vivo model of breast cancer. This suggests a new role for DCA as a cancer stabilizing agent, similar to an anti-angiogenic therapy.
However, to the authors’ knowledge, no human data has yet been published supporting the use of DCA for long-term maintenance
of stable disease. As a result of Bonnet’s groundbreaking DCA publication, in early 2007, Khan commenced the clinical use of DCA
to treat cancer patients with a poor prognosis or who failed to respond to approved cancer therapies.
A protocol of natural medications was developed to address the dose-limiting neurologic toxicity, in collaboration with a naturopathic physician (Andrews).
The oral DCA regimen that was developed included three natural medications acetyl L-carnitine[29-31], R-alpha
lipoic acid[32-34] and benfotiamine[35-37], for the primary purpose of neuropathy prevention. Observational data
collected from more than 300 cancer patients with advanced disease revealed measurable benefits from
DCA therapy in 60%-70% of cases. The neuropathy risk with inclusion of natural neuroprotective agents was
roughly 20% with 20-25 mg/kg per day dosing on a 2 wk on/1 wk off cycle. Reversible liver enzyme elevation
was noted in approximately 2% in this patient group (clinic observational data published online at www.medicorcancer.com).
A patient case illustrating the cytostatic effects of oral DCA treatment maintained over several years is
presented. This patient had a poor prognosis (median survival of 9-12 mo for stage 4 colorectal cancer using
aggressive conventional palliative chemotherapy). The patient was treated by Khan in cooperation with
the naturopathic physician Andrews, who developed a protocol comprised of natural neuroprotective agents.
A 57 years old female attended the author’s clinic (Khan) in March 2012 seeking therapy for metastatic colorectal
cancer. The patient was originally diagnosed with rectal cancer in mid-2010 when she consulted her doctor for
new constipation and low back pain. Colonoscopy was attempted, but the colonoscope could not be advanced
due to the presence of a partially-obstructing rectal tumour. Biopsy confirmed moderately differentiated
colorectal adenocarcinoma. Computerized tomography (CT) scan at the time demonstrated stage 4 disease
with multiple liver metastases up to 3 cm in diameter, possible tiny lung metastases and an annular rectal
carcinoma that was not easily measured (margins of the cancer were difficult to distinguish from the surrounding
tissues on CT scan). The patient underwent a loop ileostomy procedure to bypass the obstruction, and the
rectal tumour was not excised. Surgery was followed by chemotherapy consisting of 5-fluorouracil, irinotecan,
leucovorin and bevacizumab (FOLFIRI + bevacizumab). Initially the patient responded to chemotherapy with a
reduction in liver metastases, a reduction of the primary rectal lesion, and a reduction of blood carcinoembryonic
antigen (CEA) marker from 260.9 ng/mL before chemo to 3.5 ng/mL just prior to DCA therapy initiation. The
response to chemo then began to plateau. By the time the patient presented to the author’s clinic, chemo-
therapy was causing minimal disease reduction, and was essentially just maintaining stability.
The patient was previously healthy, and had a 20 year smoking history. She consumed alcohol on
occasion. There was a positive family history of colon cancer and gastric cancer. Medications included ongoing
chemotherapy as described, hydrogen peroxide enemas, oral vitamin C, occasional oral vitamin D, time-
release hydromorphone 32 mg twice a day, and short-acting hydromorphone 2-4 mg orally as needed for
“breakthrough” pain. There were no allergies. Functional enquiry revealed some mild mouth sores related to the
ongoing chemotherapy, mild diarrhea (expected with an ileostomy) and mild intermittent rectal bleeding. There
was aching/burning lower back and sacral pain up to 6 out of 10 intensity, and mild right shoulder-tip pain
exacerbated by chemotherapy (felt to be referred pain related to liver metastases).
Since the chemotherapy was still effective, and the patient was not experiencing any serious side effects,
the initial approach was to support the patient’s existing therapy, not replace it. An integrative plan was made in
cooperation with a naturopathic physician (Andrews). The plan consisted of addition of high dose oral vitamin
D at 10000 international units per day, a change of oral vitamin C to vitamin C 50 g intravenous (i.v.) weekly,
and addition of dichloroacetate sodium (DCA) 3000 mg i.v. (49 mg/kg) weekly (manufacturer: Tokyo Chemical
Industry, United States). To reduce the risk of DCA side effects, 3 natural supplements were prescribed:
Alpha lipoic acid (racemic) 500 mg i.v. with each DCA dose, oral R-alpha lipoic acid 150 mg 3 times a day,
oral acetyl L-carnitine 500 mg 3 times a day, and oral benfotiamine 80 mg twice a day. Infusions were
planned around chemotherapy infusions (separated by at least 2 d from chemotherapy) to avoid any potential
interference or drug interactions. Lipoic acid was not given on chemotherapy days, or within 1 d before or
after chemotherapy, since it is a powerful antioxidant and has the potential to reduce chemotherapy efficacy.
Integrative therapy began in March 2012. No side effects were noted, so DCA was increased to 4000 mg
i.v. (66 mg/kg) weekly. The only side effect noted at the higher DCA dose was mild post-infusion sedation.
Oral metformin was added to help sensitize the cancer to the chemotherapy, starting at 500 mg orally
1Indicates abnormal value. LDH: Lactate dehydrogenase; GGT: Gamma
glutamyl transferase; AST: Aspartate aminotransferase; ALT: Alanine
once a day with titration up to 500 mg 3 times a day. Pregabalin was added to help control the neuropathic
sacral pain (started 50 mg daily, titrated up to 50 mg 3 times a day). Chemotherapy side effects included
nausea and vomiting (prior to initiation of metformin), and metformin was skipped on days when the patient
felt unwell to prevent potential toxicity, should the patient become dehydrated.
Routine baseline blood tests were obtained including complete cell counts, standard metabolic panel, liver
enzymes and bilirubin (Table 1). A baseline CT scan was available, which had been performed 2 mo prior to
initiation of integrative therapy with DCA. After 4 mo of integrative therapy as described, a new
CT scan was performed (Figure 1), which was reported as “stable and unchanged”, but no measurements
were given. An incidental finding of a gallstone was noted (also stable from prior scan). The patient became
frustrated that no improvement was noted, and no detailed measurements were indicated in the CT report.
An attempt was made to obtain a positron emission tomography scan to clarify live vs necrotic tumours,
but government funding could not be obtained and the patient declined to pay privately for the scan.
After some discussion, the patient elected to continue therapy, and obtain future CT scans at a different hos-
pital. By September 2012, increasing chemotherapy side effects including fatigue, nausea and vomiting
were noted. A new CT scan revealed that all the liver lesions were “either smaller or no longer identified”. The
greatest tumour reduction was only 2 mm however (2.5 cm marker lesion in liver segment 4a reduced to 2.3
cm). There were no new lesions identified. After review of the CT scan, the patient decided to
stop all chemotherapy, as well as bevacizumab and metformin. DCA i.v. was continued, and the dose was
increased to 4500 mg i.v. weekly. Nausea and vomiting resolved.
Figure 1 Abdominal computerized tomography scan after 4 mo of integrative therapy with dichloroacetate sodium, 5-fluorouracil and natural medicines.
Three slices with various measurable liver metastases shown. A: 23 mm × 33 mm liver metastasis; B: 15 mm diameter liver metastasis; C: 11.2 mm × 25 mm liver
Pain remained under control. A new CT scan was obtained after 3 mo, which demonstrated residual
rectal tumour with stricture and proximal fecal loading (unchanged), and “liver metastases, not significantly
changed”. The patient reported mild numbness of the fingers and toes. There was a further increase
in asymptomatic liver enzyme elevations (Table 2). Both of these were diagnosed as DCA side effects.
During therapy up to this point, CEA had shown mild fluctuations, but was considered stable overall (Figure 2).
DCA therapy was interrupted for 3 mo to allow resolution of DCA side effects. During this time, only
natural therapies were given (prescribed by Andrews). Acetyl L-carnitine, benfotiamine and alpha lipoic acid
were continued to accelerate recovery of DCA neuropathy. Oral curcumin and honokiol (magnolia tree
extract) were added in an attempt to maintain cancer control. During the period when DCA was stopped,
CEA increased from 4.1 to 5.1 ng/mL (Figure 2). Mild DCA neuropathy had resolved and liver enzymes began
By March 2013, due to concern over the cost of infusion therapy, it was decided to begin oral DCA
therapy. A new baseline CT scan demonstrated a 1 mm increase in a liver segment 7 marker lesion, and a 1 mm
increase in a marker aortocaval lymph node, but was reported as “stable appearance of the colon” and “stable
liver metastases”.Oral DCA was initiated at a dose of 500 mg (8.2 mg/kg) twice a day, and neuroprotective supplements
consisting of oral acetyl L-carnitine, benfotiamine and R-alpha lipoic acid were continued. Supplements were
given continuously, and DCA was given on a 2 wk on/1 wk off cycle.
In December 2013, the pain medication was transitioned from hydromorphone to methadone 10 mg 3
times a day, for simplicity, improved pain control and cost savings.The patient continued on this regimen with regular
CT scans every 3 to 6 mo. The patient became less compliant with regular blood testing due to a busy work
schedule. She remained highly functional (ECOG level 1) with mild chronic DCA neuropathy that was controlled
and did not affect her daily function. An attempt was made to increase DCA to 500 mg 3 times a day, but
this resulted in significant asymptomatic liver enzyme elevation and increase in neuropathy. As a result, a DCA
dose of 500 mg twice a day was resumed after a brief therapy interruption.
Ongoing CT scans continued to reveal stable disease (Figure 3), with no new lesions appearing. Overall CEA
was not significantly changed from the initiation of DCA therapy (CEA of 3.5 at the start of DCA therapy, to CEA
of 3.7 after nearly 4 years of therapy). General blood panel was also favourable at the 3 year mark (Table 3)
and after the 4 year mark (Table 4).In summary, after receiving conventional chemotherapy for approximately 18 mo,
the patient received intravenous DCA therapy with concurrent chemotherapy
for approximately 6 mo, followed by intravenous and oral DCA therapy with no concurrent conventional
cancer therapy for nearly 4 years. During the treatment with oral DCA, the patient experienced stable disease
by CT scans, and stable disease by CEA tumour marker measurement. She also was clinically stable with no
escalation of methadone dose, maintenance of ECOG level 1 function, stable mild DCA neuropathy, and she
was able to run her own business successfully.
Figure 2 Graph of carcinoembryonic antigen through the course of therapy. CEA: Carcinoembryonic antigen.
Figure 3 Abdominal computerized tomography scan after 3 additional months of integrative therapy (dichloroacetate sodium + 5-fluorouracil + natural
medicines), followed by nearly 4 years of dichloroacetate sodium without any concurrent conventional cancer therapies. Scans demonstrate absence of
cancer re-growth and absence of new liver metastases. Same slices as Figure 1 are shown. A: 11.3 mm × 27.5 mm liver metastasis; B: No metastases visible; C: No
This case of DCA therapy in a patient with advanced stage 4 colon cancer demonstrates long-term stable
disease according to clinical, biochemical and radiologic criteria. The duration of stability while on DCA without
other active chemotherapy is currently 46 mo (nearly 4 years), with a survival time since the initial diagnosis
of stage 4 colorectal cancer of 6 years. Based on the National Cancer Institute’s SEER cancer statistics
review 1975-2011, the 5-year relative survival rate for females diagnosed with stage IV colon/rectal cancer
was 14.4% (http://seer.cancer.gov/csr/1975_2013/). While it cannot be definitively concluded that DCA has
been efficacious, survival for this length of time in the absence of ongoing chemotherapy would be of relatively
low probability. Cytostatic rather than cytotoxic effects of DCA on colorectal and other cancer cells have been
reported and support this clinical finding[23,27,42-44]. To date the patient remains clinically well and she remains
on DCA therapy. In addition to the maintenance of stable disease, this case demonstrates the tolerability of oral DCA in
a cancer patient for much longer time periods than those currently reported from the published clinical
trials in cancer patients. Chu et al reported on 24 patients treated for a median time of 2 mo at either
6.25 or 12.5 mg/kg BID, on continuous oral DCA without neuroprotective supplements. They concluded
that the recommended phase 2 dose was 6.25 mg/kg BID (12.5 mg/kg per day), with careful monitoring of
neuropathy being needed. Dunbar et al recommended 5 mg/kg BID as a starting dose for most patients,
with their trial administering 4, 8 or 12.5 mg/kg BID continuously (median time on DCA 34 d), also without
neuroprotective supplements. The patient in this report took 500 mg BID, equivalent to 8.2 mg/kg BID, 2
wk on/1 wk off, but could not tolerate this dose three times a day (total of 25 mg/kg per day). Dunbar et
al suggest that genotyping for polymorphisms in GSTZ1, the DCA metabolizing enzyme in the liver
which is inactivated with ongoing DCA usage, should be considered in determining the starting dose for
patients. However further work is necessary to gather convincing numbers of genotypes and dose-tolerance
data. A clinical trial of DCA in multiple myeloma patients is currently underway to contribute to this pool of
data (Australia New Zealand Clinical Trials Register #ACTRN12615000226505, http://www.anzctr.org.au).
Further studies are required to determine the optimal dosage regime for maximum tolerable acute or chronic
treatment with DCA, and indeed what dose is required for efficacy.
The case presented indicates DCA holds great promise as a cancer therapy. The patient achieved a significant
benefit from her therapy, with mild side effects and no hematological, cardiac, pulmonary or renal toxicity.
Some hepatic toxicity was observed (Table 2), which was easily managed by DCA therapy interruption
followed by dose adjustment. Mild reversible peripheral neurotoxicity was reported. Natural therapies that were
combined with DCA (acetyl L-carnitine, alpha lipoic acid and benfotiamine) assisted the patient with reduction
of side effects, but are not known to function as cancer therapies.
As of this writing, no active clinical trials exist investigating the human use of DCA as a cytostatic agent.
Due to the fact that DCA is off patent, raising adequate funds to support large scale human trials is a serious
challenge. It is hoped that this case exemplifying the benefits of oral DCA will stimulate further clinical
Based on our clinical experience, combined with existing publications, off-label DCA therapy is an
option for patients with limited available conventional treatments, once they understand and accept the risks
and benefits of therapy. This case report shows that even in advanced stage disease, DCA has the potential
to prolong life without impacting a patient’s quality of life, as compared to chemotherapy with its frequent
debilitating side effects or compromise in physiological function. Given its reasonable cost and modest toxicity,
DCA deserves further investigation.
The authors wish to thank Dr. Humaira Khan for her assistance, and also the patient for her support and
consent to publish her case.
The 57 years old female patient presented with constipation and lower back pain.
The patient was diagnosed with a partially-obstructing rectal cancer.
Elevated carcinoembryonic antigen tumour marker.
Rectal mass seen on colon colonoscopy.
Moderately differentiated colorectal adenocarcinoma.
Loop ileostomy followed by chemotherapy consisting of 5-fluorouracil, irinotecan, leucovorin and bevacizumab,
then addition of dichloroacetate sodium (DCA), then DCA without chemo for nearly 4 years.
Computerized tomography scan reports demonstrate reduction of cancer with combined chemotherapy + DCA,
then stable disease for nearly 4 years with DCA and no chemo.
DCA: Dichloroacetate sodium; RECIST: Response evaluation criteria for solid tumours; ECOG: Eastern cooperative oncology group; SEER: Surveillance,
epidemiology and end results.
Experiences and lessons
DCA is not only a pro-apoptotic drug, but may also act as a cytostatic agent, and can thus achieve long-term stabilization of advanced cancer without serious side
effects, as illustrated by this rectal cancer case.
DCA, the sodium salt of dichloroacetate, is a cheap chemical compound that has shown some clear potential as an alternative cancer treatment, which
has been used in a number of trials with people suffering from brain cancer, or glioblastoma. This is a well-written case report in which oral DCA therapy
resulted in tumor stabilization of stage 4 colon cancer in a 57 years old female for a period of over 3 years, with no serious toxicity. This report covers what it
promises to. The authors do a solid job of explaining the basics of DCA therapy and its role in different tumor types. Along with the addition of mechanisms of
action against cancer cells and therapeutic potential of DCA, the authors provide a good resource for readers who are more unfamiliar with DCA therapy but also
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