CIPNDrRusso

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The Feasibility of an Acupuncture Protocol in
the Treatment of Chemotherapy Induced
Peripheral Neuropathy - a Pilot Study
By, Alfred J. Russo, DAOM, EAMP, LAc
Abstract
Objectives: The present pilot study was performed to determine the effect of ten weeks of acupuncture treatment on the
pain and symptoms of Chemotherapy Induced Peripheral Neuropathy (CIPN).
Design: Eleven subjects completed the study that consisted of a pre-treatment and post-treatment case series design.
Changes in pain and Quality Of Life were detected using the Neuropathic Pain Scale, the QLQ-C30 and the QLQ-
CIPN20 QOL scales at week 0, 5 and 10. The acupuncture treatments occurred once a week for ten weeks. Each of the
10 sessions consisted of the subjects receiving 34 acupuncture points that address Chemotherapy Induced Peripheral
Neuropathy. Thirty-four gauge needles were placed in points located on the extremity and thirty two-gauge needles
were inserted in back points. The needles were retained for twenty minutes.
Results: The changes in QLQ and NPS testing were considered significant with a p-value < 0.05 and accepted as
positive trending if the p-value was between 0.05 and 0.1. These results provided indication of positive trending in six
QOL parameters and showed a significant change in three areas: neuropathic pain, CIPN symptoms and sensory
condition.
Conclusion: The results of this study indicate that subjective pain, symptoms of chemotherapy induced peripheral
neuropathy, and quality of life can be reduced during the period of acupuncture therapy delivered in a controlled setting.
Research Cohort for Bastyr University DAOM 2010: Erin Moran, Nicolette Behne, and Derek Kirkham.
Introduction
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect associated with several
chemotherapeutic agents that may occur during and/or after a treatment protocol. CIPN is a toxicity-related neuropathy
and presents mainly as axonopathy of sensory nerve fibres, with symptoms such as neuropathic pain, hypesthesia and
burning paresthesias; motor nerve fibres are less commonly involved (Postma & Heimans, 1998). These clinical
features of CIPN resemble those of diabetic neuropathy (Feldman, Shefner & Dashe, 2008). CIPN can significantly
reduce one’s quality of life (QOL) and may often be debilitating (Visokvsky, Collins, Aschenbrenner, Abbott & Hart,
2007).
Different chemotherapeutic agents are associated with varying rates of CIPN. In most patients, CIPN improves over
time; however, recovery is often incomplete (Siegal & Haim, 1990; Von Schlippe, Fowler & Harland, 2001). For
example, paclitaxel administration is associated with sensory neuropathy in 30-35% of patients. After completing
treatment, 50% of patients improve over a period of months, however, some patients take years to recover (Skeel, 2007;
Eisenhauer, ten Bokkel, Huinink & Swenerton, 1994). CIPN develops in 75% of patients receiving a prolonged course
of thalidomide and the neuropathy is only partially reversible (Tosi, Zamagni & Cellimi, 2005; Plasmati, Pastorelli,
Cavo, et al., 2007). Cisplatin-associated neuropathy continues to progress for several months in 30% of patients and
may even begin after therapy has been discontinued (Siegal et al, 1990; von Schlippe et al., 2001).
Currently there are no CIPN-specific interventions, only suggested pharmacological and non-pharmacological strategies
for relief of symptoms. However, acupuncture has been used in the treatment of diabetic neuropathy as well as
neuropathies stemming from HIV/AIDS. For instance, a study in the United Kingdom using acupuncture for chronic
peripheral diabetic neuropathy showed significant improvement in 77% of the 46 patients involved (Abuaisha, Costanzi
& Boulton, 1998). Ahn, et al., also reported that acupuncture decreased diabetic neuropathy-associated pain according
to the daily pain severity score (Ahn, Bennani, Freeman, Hamdy & Kaptchuk, 2007). There has only been one pilot
study performed on the effects of acupuncture in the treatment of CIPN. Wong and Sagar, 2006, treated five CIPN
patients weekly with 2 six week series of acupuncture, separated by a four week rest period. All patients reported an
improvement in pain, numbness and tingling. The average pain score was also decreased.
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This study sought to advance the understanding of acupuncture’s effect on CIPN. The hypothesis of this pilot study
was that acupuncture would reduce symptoms of CIPN and improve patients’ quality of life. The CIPN subjects were
recruited; changes in CIPN-related pain and QOL were measured following a series of acupuncture treatments. The
study took place at Whidbey Island General Hospital and Skagit Valley Oncology Center. Treatments were performed
by licensed acupuncturists. Subjects received one acupuncture treatment per week for 10 weeks. A protocol of
acupuncture points was developed to address the mechanism of neurotoxicity caused by different chemotherapeutic
agents. Neurologically, acupuncture needles have been shown to stimulate and initiate the dendrite receptors of sensory
neurons of the skin, muscle, and other tissues. Acupuncture is also known to induce homeostatic and immune system
responses (Ma, Ma & Cho, 2005). We hypothesize that acupuncture is a useful therapy for CIPN.
In the Traditional Chinese Medical (TCM) model, symptoms of CIPN may be seen as a state of Qi and Blood
deficiency, and the body’s failure to direct these essential substances to the four limbs, resulting in sensory symptoms
and impaired limb function (Wong & Sagar, 2006). The acupuncture protocol used in this pilot study was not based on
the TCM approach, where a tongue and pulse examination is done to assess the state of Qi, Yang, Yin and Blood of
each subject. The acupuncture protocol used in the pilot study included points near the spine, due to their close
proximity to the dorsal root ganglia and their ability to treat pain related to neurological disorders (Cai, 2007). The
points along the spine used in this protocol have the actions of regulating and harmonizing yin and yang. Distal points
included in the treatment protocol are commonly used in peripheral neuropathy (Deadman, Al-Khafaji, & Baker, 1998).
Literature review
Introduction
CIPN is a frequent side effect resulting from several anticancer drug therapies. Although many of these anticancer
regimens are proving successful in decreasing tumour size or metastasis, the neuropathy that often follows can be
severely debilitating and may compromise a patient’s QOL (Visovsky, et al., 2007). The incidence and severity of
CIPN varies greatly depending on the agent used. The incidence of severe CIPN is estimated to be 3-7% in people
treated with single agents and greater than 38% in those treated with a combination of agents (Cavaletti & Zanna,
2002). Recovery may take up to two years. Symptoms may worsen after certain agents are stopped. In some cases the
neurological damage is irreversible (Loprinzi & Paice, 2008). The incidence of CIPN is on the rise as a result of
increased use of high-dose chemotherapy and more combinations of neurotoxic agents (Skeel, 2007).
Symptoms of CIPN include neuropathic pain, hypesthesia and burning paresthesias. Motor nerve fibres are less
commonly involved in CIPN (Postma & Heimans, 1998).
The chemotherapeutic agents most associated with CIPN are the platinum agents (cisplatin, carboplatin, and
oxaliplatin), the taxanes (docetaxel and paclitaxel), the vinca alkaloids (primarily vincristine), thalidomide and
bortezomib (Perry, 2008; Skeel, 2007). CIPN is dose - limiting during chemotherapy treatments and when necessary,
oncologists will decrease the dosage or discontinue the use of a CIPN-causing agent altogether, switching to a less
neurotoxic agent. CIPN is a concern for both patient and clinician in terms of treatment efficacy because an increasing
number of patients are unable to complete a course of treatment due to symptoms of CIPN (Visovsky et al., 2007;
Colleau, 2008).
Currently there are no standard interventions that are recommended to treat symptoms of CIPN (Visovsky, et al., 2007;
Perry, 2007). Acupuncture, a modality in Oriental medicine is considered a possible intervention for CIPN but to date,
only one pilot study (Wong & Sagar, 2006) has been completed. Wong and Sagar used an acupuncture protocol based
on TCM whereby acupuncture points were modified based on each subject’s individual assessment. The protocol
focused predominantly on Qi, Blood, and Yang deficiency with added points to direct the Qi and Blood to the
extremities. Although the results were promising, more research is required in this area. Larger studies that can
reproduce statistically significant results would support acupuncture in the treatment of CIPN.
Neurologically, acupuncture needles stimulate sensory nerves, eliciting a response in the dendrite receptors of sensory
neurons of the skin, muscle, and other tissues. Clinical observation shows that acupuncture needling achieves
acceleration of tissue healing; release of physical and emotional stress (Ma, Ma & Cho, 2005) and therefore it may be a
useful therapy for CIPN.
Because of the neuronal effects of acupuncture, it may offer a more focused therapy for CIPN than the systemic
treatment provided by oral pharmaceutical agents. Acupuncture can be applied to treat damage to the large myelinated
fibres in the dorsal root ganglia associated with the platinum compounds, thalidomide and bortezomib, as well as the
axonopathy of the distal peripheral nerves associated with the vinca alkaloids and taxanes (Casey, Jellife, LeQuesne &
Millet, 1973; Cavaletti, Beronio, Reni, Ghiglione, Schenone, et al., 2004; Krarup-Hansen, et al., 2007; Argyriou,
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Polychronopoulos, Iconomou, Chroni & Kalofonos, 2008). The acupuncture protocol used in this study was designed to
include both local acupuncture points near the damaged peripheral nerve fibres as well as points closer to the spinal
column to treat damage at the dorsal root ganglia.
Although there is a paucity of studies of acupuncture efficacy in CIPN, there have been a number of studies performed
to assess diabetic and antiretroviral-related neuropathies. Similar to CIPN, diabetic neuropathy seems to be primarily an
axonal disorder (Feldman, Shefner, & Dashe, 2008). Clinical trials have shown that acupuncture relieves neuropathic
symptoms (Agnoletto, Chiaffarino, Nasta, Rossi & Parazzini, 2003; Phillips, Skelton & Hand, 2004). The Phillips, et
al., acupuncture protocol focused on commonly used points with a protocol modified according to the subject’s
individual TCM diagnosis. Furthermore, these treatments have been shown to help improve QOL (Chang, Boehmer,
Zhao & Sommers, 2007). The protocol used in this CIPN study did not use a TCM diagnosis as one protocol was
designed for all subjects.
Mechanisms and characteristics of CIPN
CIPN is a polyneuropathy in the sensorimotor category with a symmetrical distribution. Polyneuropathies are
differentiated from other neuropathies by the location of damage to the neuron: demyelination, mixed or axonal. CIPN
results from axonal damage caused by the toxicity of chemotherapeutic agents and shares symptomology with
metabolic, genetic and nutritional neuropathies, resulting from axonopathy of sensory nerve fibres in a stocking-glove
distribution (Misulis & Head, 2007). Although the exact pathophysiologic mechanisms are still unknown, many of the
chemotherapeutic agents responsible for CIPN interfere with neuronal tubulin (Perry, 2007). Tubulin is a cellular
protein responsible for critical cellular functioning and cell division, including the functional and replicative aspects of
peripheral nerve cells.
In summary, the main mechanisms by which various chemotherapeutic agents induce peripheral neuropathy appear to
be similar and involve damage to the distal peripheral axons or the neuron bodies in the dorsal root ganglia. The
acupuncture protocol in this pilot study may effectively increase circulation and assist in regeneration of damaged axons
and neuron bodies (Ma, Ma & Cho, 2005). The standard of care in the TCM field does not have enough developed
theories on differential diagnosis and associated treatment based on an individual’s presentation; furthermore, there is
no standard care in allopathic medicine to treat CIPN. The design of an acupuncture protocol that shows decrease
symptoms of CIPN would be an important finding and would warrant further study to provide a standard of care.
Treatment strategies for the CIPN pilot study
Acupuncture promotes tissue healing through needle manipulation (Langevin & Yandow, 2002). It stimulates
subcutaneous structures, including afferent somatic neuron fibres (cutaneous A-delta and C-fibres), sympathetic neuron
fibres, fine arterial and venous blood vessels, mast cells, lymphatic and connective tissue. Muscular tissues and nervous
tissues associated with sensory and postganglionic neurons are also affected. Acupuncture induces a micro-current that
aids in tissue growth and regeneration (Ma, Ma & Cho, 2005).
Different patients respond differently to the same acupuncture treatment. Ma, et al., (2005) suggest that acupuncture
activates the self-healing potential in one’s body and that the healing process is dynamic in the individual. The efficacy
of a treatment can therefore be different for each patient based on their individual health and their individual symptom
picture.
The acupuncture points utilized in this treatment protocol are designed to improve circulation and support homeostasis.
Some points lie close to nerves affected. For example, the spinal acupoints are referred to as Hua Tuo Jia Ji (HTJJ)
points and are 0.5 body Chinese units or cun lateral to the lower border of each spinous process, near the nerve roots
Inoue, et al., (2008). Hua Tuo was a physician in the Han dynasty and jia ji literally means “lining the spine”
(Dharmananda, 2002). Hua Tuo used these points in preference to other back points (Deadman, Al-Khafaji, & Baker,
1998. Acupuncture point stimulation close to the spinal nerve roots alleviates pain and dysesthesia. HTJJ acupoints are
important in this research treatment protocol because of their close proximity to the dorsal root ganglia and their ability
to treat pain related to neurological disorders (Cai, 2007). The use of HTJJ points have not been studied in relation to
CIPN. The point GB 34 is located just anterior and distal to the fibular head (Deng, et al. 1999), close to the bifurcation
of the common peroneal nerve.
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Methods
For this study, twelve subjects were evaluated, but one was excluded due to post-surgical lymphadenopathy. All eleven
subjects who began the research trial completed the course of treatment. The subjects in this study were on various
supplements and medications that could influence the results of their acupuncture treatment. There was no inclusion or
exclusion standard designed to address nutritional supplementation or medications.
Specific Aim 1: To determine whether a particular acupuncture point protocol alleviates CIPN symptoms and
thereby improves patients’ quality of life.
We measured the feasibility of a specific acupuncture protocol in patients with CIPN at baseline, after four weeks and
at ten weeks of treatment (final visit) using the following tools: the Neuropathic Pain Scale (NPS), the QLQ-C30 and
the QLQ-CIPN20 QOL scales. Adverse events will be monitored via the Monitoring of Side Effects (MOSES)
instrument.
Study Design
This pilot study evaluated the use of acupuncture therapy in a group of eleven participants with CIPN. Treatments
focused on quality of life, pain, and parethesia of the extremities. Acupuncture treatments were given once a week for
ten weeks. Patients were treated in the prone position with a total of 34 acupuncture points used. Total needle retention
time was twenty minutes. Sterile, single use needles were inserted at each acupuncture point, utilizing clean needle
technique. Regarding the type of needle utilized, thirty-four gauge needles were placed in points located on the
extremity and thirty two-gauge needles were inserted in back points. Needle depth was determined based on body mass
and cun measurements of the patient (Deadman, Al-Khafaji, & Baker, 1998 & Deng, L., Cheng, X., Cheng, Y., 1999).
Changes in pain and QOL were assessed using the Neuropathic Pain Scale (NPS), the QLQ-C30 and the QLQ-CIPN20
QOL scales.
Subjects:
Recruitment took place at Whidbey Island General Hospital and Skagit Valley Oncology Center via advertising and
community outreach.
Inclusion Criteria
Age 18-75 years of age
Must have been treated for cancer with chemotherapy
Must have a diagnosis of WHO Grade II or higher peripheral neuropathy or CIPN from medical oncologist
Exclusion Criteria
The following variables were excluded to minimize confounding factors to better assess the benefits of acupuncture
with CIPN:
Subjects receiving additional acupuncture treatments during the course of the study.
Subjects receiving additional CIPN-focused treatments by other health care providers.
Further exclusion criteria:
Pre-existing peripheral neuropathy. For example, PN due to anti-retroviral drugs, diabetes mellitus, or alcoholism.
Currently pregnant or planning to conceive during the study.
Consent
A consent form was given to the potential participants to sign prior to the beginning of the study. The participants were
provided an explanation of the consent process, given an opportunity to ask questions and then had 24 hours to review
and sign the form.
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Research Setting
The study took place at Whidbey Island General Hospital and Skagit Valley Oncology Center. The primary licensed
acupuncturist at Whidbey Island is currently employed by the hospital and performed acupuncture for the subjects
recruited at this site. At the Skagit Valley clinic, subjects were treated by licensed acupuncturists and doctoral
candidates in the School of AOM at Bastyr University and were supervised by a doctoral supervisor who is also a
licensed acupuncturist.
Procedures
Acupuncture Points:
The following 34 acupuncture points were needled with even technique and retained for twenty minutes. The Hua Tuo
Jia Ji, (Paravertebral Points) are located 0.5 to 1 body units lateral to the depression below the spinous processes of the
twelve thoracic and five lumbar vertebrae. There are 17 points in all. In this study, cervical levels five; six; seven;
thoracic level one; and lumbar level four and five were included on the treatment protocol. Cervical points are not
classical HTJJ points, but are often used clinically to treat similarly to the thoracic and lumbar. HTJJ are needled 0.5 to
1 body units deep. The needle is inserted perpendicular with a slightly oblique and medial angle.
UB 32, (Ci Liao) is located in the second posterior sacral foramen and is needled 1.5 to 2 body units, perpendicular with
a slight oblique medial, and inferior insertion.
Ba Xie are located between the metacarpal heads proximal to the web margin, and the thumb and index metacarpals,
proximal to the web of the hand. These points are needled 0.5 to 1 body units, perpendicular between the metacarpal
bones.
Ba Feng, are located on the dorsum of the foot, between the toes, 0.5 body units proximal to the margin of the web, and
are needled 0.5 to 1 body units, obliquely and proximally.
LI 10 (Shou San Li) is located 2 body units distal to LI 11 (Qu Chi), on the line connecting LI 11 to LI 5 (Yang Xi), and
is needled perpendicularly 0.5 to 1 body units.
GB 34 (Yang Ling Quan), is located approximately 1 body unit anterior unit inferior to the head of the fibula, and is
needled perpendicularly1 to 1.5 body units (Deadman, Al-Khafaji, & Baker, 1998).
Pain Assessment
In order to detect changes in CIPN-related pain as a result of acupuncture treatments, the validated neuropathic pain
scale (NPS) was used. This scale assessed the subjective quality of the neuropathic pain that participants reported. The
scale consists of ten questions, asking participants to assess different aspects of their neuropathic pain by marking a
number between zero and ten (Galer & Jensen, 1997). This tool is not specifically designed for CIPN. The NPS was
administered prior to the first treatment, and after the fourth and last treatments.
Quality of Life Assessment
Changes in Quality of Life (QOL) were assessed using the QOL questionnaire, which is a combination of the QLQ-C30
and QLQ-CIPN20 instruments. The QLQ-C30 is a validated tool and the QLQ-CIPN20 has completed phase three of its
development process and is ready to be utilized in clinical trials (Aaronson, et al., 1993; Postma, et al., 2005; Salvo, et
al., 2009). The QLQ-C30 assesses the QOL of participants who are diagnosed with cancer. The scale consists of thirty
questions. Participants were asked to answer each question by circling a number between one and four. The QLQ-
CIPN20 is specifically designed for patients with CIPN; it consists of twenty questions and uses the same numerical
scale as the QLQ-C30. Each subject completed these questionnaires prior to their first treatment, and after their fourth
and final acupuncture visit. In addition, participants completed weekly tracking forms with questions regarding other
modalities used, for example massage from their therapist, medications, and any adverse effects resulting from
acupuncture.
Statistical Analyses
Due to the pilot design and the nature of this study, a power analysis was not included. However, each test that was
utilized had the potential for positive trending and significance if a p-value of <0.05 was accepted as significant.
Multiple comparisons of NPS and QLQ data over time were accomplished using ANOVA and the Mann-Whitney U
tests.
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Results
The gender and age distribution of the subjects in the pilot study are reported in table 1 below. The mean age of the
subjects was 65.9 years. There were eleven subjects in all, three male and eight female. Three subjects (27%) received
treatment at the Whidbey Island General Hospital (WIGH) and eight subjects (73%) from the Skagit Valley Hospital
Regional Cancer Care Center (SVHR) site.
Table 1: Gender and ages of the subjects
Subjects Gender Age
1 M 74
2 F 71
3 F 60
4 F 47
5 F 59
6 M 63
7 F 74
8 F 73
9 F 73
10 F 61
11 M 70
Mean Age 65.9
These results provide indication of positive trending in six QOL parameters and show a significant change in three areas
(neuropathic pain, CIPN symptom and sensory condition) out of 122 tests performed. A summary is provided below in
table 2. Due to the small sample size and large number of statistical analyses run, some of these findings, while
compelling, may have occurred by chance. Based on these findings the results of the study cannot be generalized to any
group or population. Nonetheless, the preliminary data gathered from this study will set the stage for a larger controlled
trial
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Table 2. Results: Significant and positive trends
Question p-value
(Mann-
Whitney)
p-value
(ANOVA)
NPS
How intense is your surface
pain?
(scale 0-10)
0.0278* 0.0636‡
QLQ-30
Has your physical condition or
medical treatment interfered with
your social activities?
(scale: Not at all 1- Very much
4)
0.0356* 0.2249
QLQ-30
During the past week were you
limited in doing either your work
or other daily activities?
4)
0.131 0.095‡
QLQ-30
Role Functioning Scale
0.0569‡ 0.2406
QLQ-30
Cognitive Functioning Scale
0.2643 0.0942‡
QLQ-30
Social Functioning Scale
0.0565‡ 0.4114
QLQ-30 CIPN20
During the past week did you
have difficulty distinguishing
between hot and cold water?
4)
… 0.095‡
QLQ-30 CIPN20
CIPN Sensory Scale
0.0126* 0.2429
*p<0.05 considered statistically significant
‡0.05<p>0.10 positive trending
… Data could not calculated
Discussion
The acupuncture protocol in this CIPN study was used to promote blood flow and nerve regeneration. Acupuncture
functions by stimulating many subcutaneous structures, including: afferent somatic neuron fibres, sympathetic neuron
fibres, fine arterial and venous blood vessels, mast cells, lymphatic and connective tissue. Muscular tissues and nervous
tissues associated with nerve fibres of sensory and postganglionic neurons are also affected by acupuncture treatment.
Acupuncture has also been shown to be effective by inducing a microcurrent which aids in tissue growth and healing.
In regards to study limitations, acupuncture is one of several modalities within TCM. Many TCM practitioners in
clinical practice also include Chinese herbology, moxabustion (heat therapy), and tuina (Chinese therapeutic massage).
This study protocol was limited to assessing acupuncture. Future studies may include assessing additional modalities for
their impact on CIPN, including Chinese herbs, moxabustion, and tuina. A future study should include a control arm.
One possible control would be standard care for CIPN.
This CIPN study included subjects with both acute and chronic CIPN. Subjects with acute CIPN were still undergoing
chemotherapy, and thus continued to experience ongoing nerve trauma while receiving the acupuncture protocol.
Acupuncture may have had a more temporary effect in these study participants due to their ongoing chemotherapy.
Subjects with chronic CIPN were no longer undergoing chemotherapy. As these subjects were not being exposed to
chemotherapeutic agents that could exacerbate their CIPN, their symptoms should no longer increase on their own,
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although subjects who were administered vincristine may continue to worsen after active chemotherapy had been
discontinued. In the future, limiting study participants to only chronic CIPN would decrease the confounding variables.
The root and branch concepts were taken into consideration when creating the CIPN protocol in this pilot study;
however, a TCM diagnosis was not made to modify the treatment based on individual variations of the root and branch
diagnosis. Acupuncture was originally meant to focus on the body as a whole when considering the TCM assessment.
In this study the focus was directed towards the symptoms of CIPN without considering a pattern differentiation. By
using a single protocol the potential for confounding variables is reduced, but a single protocol does not fit everyone.
When designing a research protocol such as this pilot study, there is an inherent conflict between the reductionist
outlook of the researcher and the highly variable practice conditions of the clinician.
Wong and Sagar; Phillips, Skelton and Hand; Jiang, et al.; Ahn, Bennani, Freeman, Hamdy and Kaptchuk ; Abuaisha et
al., all used acupuncture protocols that were based on TCM, and were modified for each subject’s diagnosis. Shlay,
Chaloner, Max, Flaws, Reichelderfer, et al., did not determine a TCM assessment and limited acupuncture to the legs
and feet.
This CIPN study was based on the known mechanisms of damage from medications. In subjects where the
chemotherapeutic agent damaged the dorsal root ganglia, the treatment of the HTJJ would be considered treating the
root and treating the manifestation would be the treatment of the branch. Where the chemotherapeutic agent damaged
the hands and feet directly, then acupuncture at the local points would be considered treating the root rather than branch.
Thus, manifestation of the disease in both root and branch cases is still the hands and feet.
Needle retention time and the order of needle insertion were not clearly defined. Other studies included retention of
acupuncture needles ranging from twenty to forty-five minutes. The retention time in this study was twenty minutes.
The starting point of the needle retention period was not clearly stated in our study, increasing the potential for error.
The start could technically begin at the insertion of the first or last acupuncture needle. Longer retention times for some
locations may have increased the observed therapeutic effect. Furthermore, the order of needling was not specified.
These variables may have impacted the results.
Acupuncture was administered to subjects on a weekly basis for ten weeks. In other reviewed neuropathy studies,
acupuncture was administered biweekly to daily. In China, treatments are typically administered daily and up to five
days a week. The US health care reimbursement issues make daily treatment difficult. However, increased frequency in
visits would possibly increase effectiveness of treatment and may be necessary to yield significant results.1
It would also
clarify how acupuncture would best serve the population in results with pain and be cost effectiveness.
The acupuncture protocol was modified for three subjects in the study. The gauge of the acupuncture needle was
decreased to accommodate for pain during insertion for two subjects and post treatment for one subject. Subjects
continued to receive the same acupuncture protocol, but results may not be consistent due to the change in the needle
gauge.
The protocol for administering the questionnaire was modified in this study, which was a mistake of the researchers.
Pilot study researchers asked the subjects the questions instead of having them fill out the forms themselves. This may
introduce bias because answers were not anonymous. In future studies, subjects should complete questionnaires in
private, unless there are extenuating circumstances.
Below are a few examples of subjective results. Many of the research subjects commented that there was an
improvement in symptoms and in their overall quality of life. The quotes may not comprehensively capture their
experience, but they do describe the experience of treatment and other areas regarding changes in quality of life. There
may also be bias in the quotes because they were asked directly by one of the researchers at the end of their last visit.
Not all changes that patients experienced were reflected in the questionnaires and the researchers in this CIPN study
asked the subjects to write in their own words, their interpretation of the treatment results.
“Overall feels improvement, especially in the hands, about 40% improvement and about 30% improvement in the feet”.
“Not much improvement in CIPN, but I think it is more from my lymphadema. The treatments helped me generally feel
better and my lymphadema improved as a result of acupuncture”.
“Heels do not feel as spongy as the front of the foot. Heels feel more awake. At start of the treatment the whole foot felt
like soggy, like spongy balls and now only feel this at the toes. Feel more stable on my feet”.
1
Hubei College of Traditional Chinese Medicine acupuncture observation, 2005
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“Feel a lot better sensation in finger and toes, about 75% improvement”.
“Energetic, has really felt great overall with a lot more energy. The feet feel warmer the last three weeks. Left foot, felt
tingling in the last three toes and never felt this before. Week eight, feet felt itchiness on top”.
There was no pattern seen in the supplements or medications taken in the study. Subjects recorded taking steroids,
antiemetics, narcotics, anti-depressants, and other chemotherapy-related medications that are not directly related to
CIPN. In future studies testing one acupuncture protocol with a specific regimen of chemotherapy agents would reduce
the number of confounding variables.
There were disadvantages to the evaluation tools used, so the results may not be representative of the change in the
study. There could be added assessment parameters that further evaluate the Quality of Life. The tools chosen were
used because they were the best validated questionnaires available at the time of the study. The researchers in this study
did not have the resources and time to validate new questionnaires specific to study. The tools themselves are not well
developed because researchers and clinicians do not understand how to fully represent the symptoms associated with
CIPN into an assessment form.
The data collection from patients’ can be evidence that health-care professionals tend to underestimate and underreport
the severity and frequency of CIPN, especially the subjective symptoms such as fatigue and numbness, which impact on
the patient’s Quality of Life. Better instruments to measure the severity of toxic neuropathy are needed for clinical
management and for trials of preventive interventions. These instruments need to fulfil strict biometric requirements,
including simplicity, responsiveness, reproducibility and meaningfulness (Hughes, et al., 2008; Cavaletti, et al., 2009).
Several initiatives have recently been launched to address all these unsolved issues regarding CIPN assessment. The
most important among them has been the first Clinical Trial Planning Meeting on CIPN organized by the National
Cancer Institute (March 23rd, 2009 – Rockville, MD) involving oncologists, neurologists, pain experts and the
collaborative CI-Perinoms study. The CI-Perinoms study compares outcome measures in CIPN currently and ongoing
in ten European/North American countries. This study has twenty-two oncological and neurological departments
involved (CI-Perinoms Study Group, 2009). There was a conviction amongst various health-care professionals that
honouring the patient’s perspective was the right way to achieve an adequate response to this medical need. Until this
need is filled, it is an opinion of researchers and health care providers to use the Total Neuropathy Score combined with
a reliable QOL questionnaire (i.e. the EORTC QLQ-CIPN20), and a simple pain assessment (i.e. using a visual-
analogue scale). This modification in CIPN assessment would allow for an effective description of the type and severity
of CIPN symptoms (Cavaletti, et al., 2009).
The incidence of severe CIPN is estimated to be lower in subjects treated with single agents and greater in those treated
with a combination of agents. Recovery may take up to two years, may worsen after certain chemotherapy agents are
stopped, and sometimes the neurological damage is irreversible. Many of the subjects in the study were on
combinations of CIPN causing medications, as well as narcotics, and other treatments to help with their peripheral
neuropathy. The acupuncture results may not be representative of an effective method of treatment given the variations
in treatment plans in place for each subject.
Summary Statement
This CIPN study’s goal was to advance the understanding of acupuncture’s effect of CIPN. The results of the study
provided indication of positive trending in six QOL parameters and showed a significant change in three areas:
neuropathic pain, CIPN symptoms and sensory condition. This indicates that subjective pain, symptoms of
chemotherapy induced peripheral neuropathy, and challenges with quality of life can be reduced during a period of ten
weekly acupuncture treatments. Several of the subjects chose to continue acupuncture treatment after the study was
completed because the change in their symptoms was significant enough to warrant continued treatment.
In the future, studies may include assessing additional traditional Chinese medicine modalities for their impact on
CIPN, including Chinese herbs, moxabustion, and tuina. Further studies could also evaluate the effect of patients’ with a
specific type of cancer, a specific chemotherapy combination, and a TCM approach.
A special thanks to Bastyr University and the faculty of the Doctor of Acupuncture and Oriental Medicine curriculum.
9

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