Does Acupuncture Potentiate
Chemotherapy In Cancer Patients?
Brenda Golianu, MD
Elizabeth Sebestyen, MD

ABSTRACT
Background Cancer patients may benefit from complementary or alternative medical therapies. Electrical acupuncture may be a modality that potentiates chemotherapy.
Objective To describe the use of electroacupuncture as a complementary modality in combination with chemotherapy in the treatment of three types of cancer.
Design, Setting, and Patients Case series between May 2002 and July 2004 at two US centers including patients with mucoepidermoid carcinoma of the parotid gland, small cell lung cancer, and metastatic ovarian cancer.
Intervention Points were chosen along meridians surrounding the cancer and metastatic sites. Positive polarity was oriented proximally and cephalad to the tumor site, while negative polarity was oriented distally, along the extremities, on the same meridian.
Main Outcome Measure Alteration of tumor growth.
Results In all three cases, the tumors had a response to chemotherapy that exceeded expectations or previous response patterns.
Conclusions Electroacupuncture may be a useful adjunct to conventional chemotherapy. Further research is needed, both in the laboratory and in randomized controlled clinical trials, to measure efficacy and explore mechanisms of action.
KEY WORDS
Electroacupuncture, Cancer, Complementary Medicine, Chemotherapy, Acupuncture

INTRODUCTION
Complementary therapies can be useful adjunctive modalities in the treatment of many cancers. Between 7% and 36% of cancer patients use complementary therapies while being treated for cancer, when these services are covered by their insurance.^1,2 There is a need for further research into the efficacy of complementary therapies.³ Several studies have reported that acupuncture can be effective in the treatment of chemotherapy-related nausea and vomiting, post-chemotherapy fatigue, and cancer-related pain.^4-6 Some recent human and animal studies have reported that adjunctive electrical acupuncture may be effective in enhancing chemotherapy.^7-9 We present 3 cases in which electroacupuncture was added to the conventional chemotherapy treatment planned for the patient and may have played a synergistic role.

METHODS
Needling
Needling technique was determined by following a protocol practiced by Dr. Jin Zhui and Dr. Qian Xin at the Guang Zhou Medical School in the People's Republic of China for the treatment of patients with metastatic cancer. The protocol is based upon the hypothesis that a positive charge surrounding the tumor destabilizes the tumor cell membranes, rendering them more susceptible to chemotherapy.

First, the meridians that pass through or around the tumor are located. Points along these meridians are selected that are 1-2 cm proximal to the known tumor sites on those meridians. They are needled using the Flying Needle insertion technique (quick insertion using wrist action), with a dispersion method (slight counterclockwise rotation). These points receive a positively charged electrical stimulus. Distal points are selected by locating major points on each meridian, preferably on the arms or legs, and are used to ground the circuit. The positive clip of the stimulator is connected to the proximal needle and the negative clip to the distal needle of the same meridian. A Chinese Multipurpose Electrical Stimulator was used (Wujin Great Wall Medical Device Co). The following specifications were used: continuous pulse duration Tao = 0.5 (±0.15) ms; repeated pulse frequency selectivity g=1-100 Hz; output peak voltage Vp1>= 40V±10V at a 500-ohm load. The stimulator produced a low-intensity and low-frequency (0.5-2 Hz) pulsed current for 25 minutes.

All needles were 34 gauge, 30-mm stainless steel. They were placed to elicit a De Qi sensation and subsequently rotated as described below. The treatment was performed 2-5 times per week for 30 minutes each time. The treatments continued for 4 months for the 1st patient, 2 months for the 2nd patient, and 7 months for the 3rd patient. During this time, the patients continued treatment with conventional chemotherapy as prescribed by the treating oncologist.

Calibration Techniques
Using a conventional oscilloscope, calibrated according to the manufacturer's recommendations, we measured the electrical output of the Chinese Multipurpose Electrical Stimulator. We used a frequency of 2 Hz. The waveform was a square wave with an average magnitude of 70 mV and duration of 0.5 ms.

CASE REPORTS
Case 1
A 43-year-old man was diagnosed with T3N2bM1 poorly differentiated mucoepidermoid carcinoma of the parotid gland and had undergone right parotidectomy and radical neck dissection with 2 positive nodes. It was not possible to obtain clear tumor margins. Following surgery, a positron emission tomography (PET) scan prior to initiation of chemotherapy showed hypermetabolic left submental and left jugular lymph nodes, innumerable hypermetabolic foci within thoracic vertebral bodies (C3, T12-L4), ribs, sternum, right ischium, and right acetabulum, suggesting osseous metastatic disease. An extensive uptake of glucose suggested involvement of the majority of the L4 vertebral body. The patient was advised that chemotherapy would not be effective for this tumor but was offered it nonetheless as a palliative modality. The patient underwent 3 courses of chemotherapy consisting of carboplatin and 5-fluorouracil, lasting 3 months. During this time he also underwent acupuncture treatment 5 times per week for 30 minutes (Table 1).

Table 1.  Points Used in Case 1 Meridian Positive Points  Negative Points Points With Electrical Stimulation ST 1, 2, 34 12, 11, 36 GB 30 39 TH 20 5 SI 19 11 BL 10 23 LI 4 20 Hua Tuo Jia Ji Points C2, T1, T10, L3 C7, T9, L2, BL 57 Points Without Electrical Stimulation* SP 6 sedation mode KI 3,7 tonification mode LR 3 sedation mode CV 17 tonification mode *Sedation mode refers to hand manipulation in a counterclockwise direction; tonification mode, hand manipulation in a clockwise direction. Figure 1. Iodine-123 metaiodobenzylguanidine (MIBG) scan of case 1 before treatment Note multiple areas of uptake (representing metastatic sites) including sternum, ribs, and thoracic and lumbar vertebrae. Figure 2. MIBG scan of case 1 after 4 months of chemotherapy and acupuncture. Only 1 area of active uptake at T8 is shown.

During treatment, recurrent hyperemia was noted at the tumor site, which resolved after acupuncture treatment, but recurred after 24 hours. The treatments continued 5 times per week for 4 months. Follow-up PET scan 4 months later showed persistent hypermetabolic activity at T8 only (Figures 1 and 2). This was the only active metastatic disease. The multiple lesions seen on prior PET scan did not show any hypermetabolic activity on this follow-up study.

Case 2
A 73-year-old woman was diagnosed with stage IV small cell lung cancer, with multiple liver metastases, periportal, mesenteric, and para-aortic lymphadenopathy. The initial lung mass was 6 cm in diameter. The patient received 6 cycles of carboplatin and etoposide, resulting in decreased tumor size to 4 x 3 cm measured by computed tomography (CT). Electroacupuncture was added 2 times per week (Table 2) to the chemotherapeutic regimen. Seven months later, the patient interrupted both chemotherapy and acupuncture for a trial of a dietary regimen. Eight months after diagnosis, the tumor measured 4.5 x 3.7 cm on follow-up CT. Chemotherapy was restarted with ironotecan for 4 cycles and the patient restarted acupuncture treatments 5 times per week. The acupuncture treatment protocol is shown in Table 2. Ten months after diagnosis, the central lung mass decreased to 3.0 x 1.0 cm. There was a marked improvement in the liver metastases and near complete resolution of the periportal, mesenteric, and para-aortic lymphadenopathy.

Table 2. Points Used in Case 2 Meridian Positive Points Negative Points  Points With Electrical Stimulation KI  27, 21 22, 3 ST 3, 19 18, 36 SP 20 3 LR 14 2 GB 24 39 LU 1 9 Points Without Electrical Stimulation* KI 7, 10 tonification mode SP 6, 9,10 sedation mode LR 3 sedation mode LI 4 sedation mode CV 17, 18 tonification mode *Sedation mode refers to hand manipulation in a counterclockwise direction; tonification mode, hand manipulation in a clockwise direction.

Case 3
A 69-year-old woman was diagnosed with stage IV ovarian adenocarcinoma, multiple liver metastases, and periaortic and pelvic lymph node involvement bilaterally. She underwent bilateral oophorectomy and started low-dose chemotherapy with carboplatin and taxol for 7 cycles with stabilization, but no improvement of the liver lesions or lymphadenopathy.

Six months later, electroacupuncture was added 2 times per week according to the protocol shown in Table 3. Repeat PET scan 13 months later showed complete resolution of both liver metastases and lymphadenopathy.

Table 3. Points Used in Case 3 Meridian Positive Points  Negative Points  Points With Electrical Stimulation KI 21, 12 16, 3 ST 19, 29 25, 36 SP 21 3 LU 9 1 LR 14 2 GB 24 39 Points Without Electrical Stimulation* KI 7, 10 tonification mode SP 6, 9, 10 sedation mode LR 3 sedation mode LI 4 sedation mode CV 17, 18 tonification mode *Sedation mode refers to hand manipulation in a counterclockwise direction; tonification mode, hand manipulation in a clockwise direction.

DISCUSSION
Although these 3 cases obviously do not allow us to draw any definitive conclusions, we report these findings because the use of electroacupuncture merits further research. We cannot determine whether electroacupuncture was responsible for tumor regression. The chemotherapy itself may have been entirely responsible for the observed phenomena, although these results were significantly better than those that were expected. If acupuncture played some role in tumor regression, the mechanism is speculative.

Electrical stimulation of sympathetic nerve endings may stimulate vasoconstriction or stimulate an immune response. There is some evidence that acupuncture may be able to affect the sympathetic and parasympathetic nervous systems.^10,11 Recent interest in influencing angiogenesis and tumor blood supply^12,13 suggests that using methods that create vasoconstriction may have a role in treatment. A recent animal experiment showed that electroacupuncture enhanced natural killer cell activity in rats, and that this enhancement was suppressed by anterior hypothalamic lesions in the animals.¹⁴ Electroacupuncture may also improve immune function in humans.¹⁵ Another possible mechanism might be that daily one-on-one time with the patient for 30 min-utes could have elicited a powerful placebo effect.

CONCLUSIONS
Acupuncture can be a useful modality to complement conventional cancer treatment and may potentiate the effects of chemotherapy. Further research is needed to determine efficacy and the mechanisms of action.  The results of these case reports are preliminary, and we are aware of the many limitations of these reports. We plan further exploration of this phenomenon in animal models, and with a larger sample of patients in a prospective, randomized controlled trial.

ACKNOWLEDGEMENTS
We wish to thank the American Academy of Medical Acupuncture (AAMA). Some of these cases were presented at the 2004 annual meeting and received 1st place for original research. We also wish to thank Drs Nancy Federspiel, Elliot Krane, Emily Ratner, and Richard Niemtzow for their energetic advice and support.

REFERENCES

1. Lafferty WE, Bellas A, Baden AC, et al. The use of complementary and alternative medical providers by insured cancer patients in Washington State. Cancer. 2004;7(100):1522-1530.
2. Molassiotis A, Fernandez-Ortega P, Pud D, et al. Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol. 2005;16:655-663.
3. Kerr C. The issue of complimentarily. Lancet Oncol. 2004;5(5):262.
4. Vickers AJ, Straus DJ, Fearon B. Acupuncture for post chemotherapy fatigue: a phase II study. J Clin Oncol. 2004;9(22):1731-1735.
5. Shen J, Wenger N, Glaspy J, et al. Electroacupuncture for control of myeloablative chemotherapy-induced emesis. JAMA. 2000;284(21):2755-2761.
6. Alimi D, Rubino C, Pichard-Leandri E, et al. Analgesic effect of auricular acupuncture for cancer pain; a randomized, blinded, controlled trial. J Clin Oncol. 2003;21(22):4120-4126.
7. Xin YL, Liu DR, Meng X. Combined electro-acupuncture with liver artery intubation in treatment of massive liver cancer. Hepatobiliary Pancreat Dis Int. 2002;1(3):397-400.
8. Manabe M, Mie M, Yanagida Y, et al. Combined effect of electrical stimulation and cisplatin in HeLa cell death. Biotechnol Bioeng. 2004;6(86):661-666.
9. Isobek K, Shimizu T, Nikaido T, Takaoka K. Low voltage electrochemotherapy with low-dose methotrexate enhances survival in mice with osteosarcoma. Clin Orthop. 2004;426:226-231.
10. Hidetoshi M, Uchida S, Ohsawa H, et al. Electro-acupuncture stimulation to a hindpaw and a hind leg produces different reflex responses in sympathoadrenal medullary function in anesthetized rats. J Auton Nerv System. 2000;79:93-98.
11. Haker E, Egekvist H, Bjerring P. Effect of sensory stimulation (acupuncture) on sympathetic and parasympathetic activities in healthy subject. J Auton Nerv System. 2000;79:52-59.
12. Sivakumar B, Harry L, Paleolog E. Modulating angiogenesis: more vs less. JAMA. 2004;292(8):972-977.
13. Sersa B, Krzic M, Sentjurc M, et al. Reduced blood flow and oxygenation in SA-1 tumors after electrochemotherapy with cisplatin. Br J Cancer. 2002;9(87):1047-1054.
14. Hahm ET, Lee JJ, Lee WK, et al. Electroacupuncture enhancement of natural killer cell activity suppressed by anterior hypothalamic lesions in rats. Neuroimmunomodulation. 2004;11(4):268-272.
15. Ye F, Chen S, Liu W. Effects of electro-acupuncture on immune function after chemotherapy in 28 cases. J Tradit Chin Med. 2002;22(1):21-23.

AUTHORS' INFORMATION
Dr Brenda Golianu is an Anesthesiologist and maintains an Anesthesiology and Acupuncture practice at Stanford University Hospital in Stanford, California.
Brenda Golianu, MD*
Stanford University, Dept of Anesthesia
300 Pasteur Dr
Stanford, CA 94305
E-mail: bgolianu@stanford.edu

Dr Elizabeth Sebestyen's specialty is Internal Medicine, and she maintains a private practice in Internal Medicine and Acupuncture in
Denver, Colorado.
Elizabeth Sebestyen, MD
1601 E 19th Ave, #3700
Denver, CO 80218
E-mail: elizabethsebestyen@yahoo.com

*Correspondence and reprint requests

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