Moxibustion as Supportive Therapy for Opioid-Induced Constipation in Patients with Advanced Cancer: A Case Series

Introduction

Opioid analgesics such as morphine, fentanyl, oxycodone, methadone, tapentadol, and hydromorphone are indispensable for cancer pain management. However, their use is often accompanied by tolerance and adverse effects. Among these, constipation is the most frequent, occurring in more than half of patients receiving opioids.^1,2 Unlike nausea or drowsiness, constipation does not improve spontaneously over time, and therefore continuous management is required during opioid therapy. The mechanisms of opioid-induced constipation (OIC) include inhibition of small intestinal motility, reduction in digestive secretions, increased stool viscosity, impaired colonic propulsion, and enhanced anal sphincter tone. ²

In clinical practice, dietary modification and lifestyle management alone are often insufficient. Pharmacological approaches such as laxatives and, more recently, peripherally acting μ-opioid receptor antagonists (PAMORAs), such as naldemedine and methylnaltrexone, are essential.^3,4 Nonetheless, patients frequently continue to experience difficult-to-manage constipation, alternating with diarrhea, and in severe cases require invasive interventions such as manual disimpaction or enemas. These situations increase physical and psychological distress for patients, as well as the burden on caregivers and health care providers.

Current Japanese guidelines mention nonpharmacological strategies such as abdominal massage and acupoint stimulation but conclude that the evidence supporting acupuncture for constipation remains insufficient.^3–7 On the contrary, international guidelines highlight integrative approaches. The American Society of Clinical Oncology (ASCO) and the Society for Integrative Oncology (SIO) recommend nonpharmacological interventions, including acupuncture, as a part of integrative care for cancer survivors.^8,9 The Oncology Nursing Society (ONS) guidelines also suggest acupuncture and electroacupuncture for constipation within the context of clinical trials. ¹⁰ This discrepancy underscores the need for additional real-world clinical evidence, particularly in Asian populations.

Recent studies have begun to provide evidence for the role of acupuncture in OIC. Olson et al. reported symptomatic improvement in a patient with OIC when acupuncture was used in addition to pharmacotherapy. ¹¹ Yildirim et al. demonstrated in a randomized controlled trial (RCT) that acupressure significantly improved stool frequency, stool consistency, and quality of life (QOL) in cancer patients with OIC. ¹² Wang et al. reported in a multicenter RCT that electroacupuncture improved OIC symptoms and QOL. ¹³ Furthermore, systematic reviews and meta-analyses support the efficacy and safety of acupuncture and moxibustion for constipation, gastrointestinal dysfunction, and chemotherapy-related side effects.^14–16 Yang et al. also summarized recent progress in integrative oncology, including the potential role of acupuncture and moxibustion in cancer care. ¹⁷ Moxibustion is a traditional thermal therapy widely practiced in East Asia, particularly in Japan, China, and Korea. Although it is less commonly incorporated into mainstream oncology and palliative care outside Asia, it is available in some countries through integrative medicine, acupuncture, or complementary therapy services. These findings suggest that acupuncture and moxibustion may be promising supportive options for OIC, warranting further clinical research. Given the limited availability of clinical data on moxibustion for OIC, case series may provide important preliminary evidence to inform future trials. Therefore, we conducted a case series to describe the clinical outcomes of moxibustion as a supportive therapy for OIC in patients with advanced cancer.

Materials and Methods

Intervention

Moxibustion was administered twice weekly for three weeks (six sessions in total) according to a standardized protocol (Table 1). A ceramic electric warming device (Seirin Corporation, Japan) was applied to deliver thermal stimulation to the following acupuncture points: abdominal points (ST25, Tianshu; ST27, Daju; CV4, Guanyuan; CV9, Shuifen; CV12, Zhongwan; SP14, Fujie), hand points (LI4, Hegu; HT7, Shenmen), and foot points (ST36, Zusanli; SP4, Gongsun; SP6, Sanyinjiao; KI6, Zhaohai; LR3, Taichong).

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Table 1.

Protocol for Moxibustion Treatment of Opioid-Induced Constipation in Patients with Cancer Pain

Protocol	Contents
Treatment	Moxibustion
Device	Ceramic Electric moxibustion (Seirin Co.) Temperature: 46–49°C Stimulation duration: Three seconds per application Repetitions: Six repetitions per acupoint
Intervention period	Twice a week for three weeks (six sessions) Followed up for four weeks after treatment
Acupuncture points	Abdomen (ST25, Tianshu; ST27, Daju; CV4, Guanyuan; CV9, Shuifen; CV12, Zhongwan; SP14, Fujie), Hands (L14, Hegu; HT7, Shenmen), Feet (ST36, Zusanli; SP4, Gongsun; SP6, Sanyinjiao; KI6, Zhaohai; LR3, Taichong)
Assessment	CAS, Constipation assessment scale; ESAS, Edmonton symptom assessment scale; BSFS, Bristol Stool Form Scale; Laxative dosage

Results

The baseline characteristics and concomitant medications of the 10 patients are summarized in Table 2. All patients completed the treatment protocol and follow-up, and no adverse events such as skin reactions, worsening of pain, or fatigue requiring discontinuation were observed. At baseline, all patients were receiving pharmacologic bowel regimens, including stimulant laxatives, osmotic agents, and/or stool softeners. Seven of ten patients (70%) were receiving naldemedine (Symproic®), a PAMORA.

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Table 2.

Baseline Characteristics

Characteristics	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7	Case 8	Case 9	Case 10
Age, y	75	69	36	74	48	73	64	74	74	77
Sex	Female	Male	Male	Female	Male	Male	Male	Male	Male	Female
Education level	Associate degree	Associate degree	Bachelor degree	High school diploma	Associate degree	High school diploma	Bachelor degree	High school diploma	High school diploma	High school diploma
Occupational status	Retired	Employed	Employed	Retired	Employed	Employed	Employed	Retired	Employed	Retired
Marital status	Unmarried	Married	Married	Married	Unmarried	Married	Married	Married	Married	Married
Hospitalization Status	Outpatient	Outpatient	Inpatient	Outpatient	Inpatient	Outpatient	Inpatient	Outpatient	Inpatient	Inpatient
ECOG performance status	1	1	2	1	2	2	2	0	2	2
Type of primary cancer	Pancreas	Pancreas	Head and neck	Pancreas	Colorectal	Bile duct carcinoma	Oral cavity	Lung	Lung	Esophageal
Opioid dose; Mean total daily dose of opioid type at baseline, mg	Fentanyl, 1.5	Oxycodone, 5	Hydromorphone, 24	Oxycodone, 80	Methadone, 30	Fentanyl, 2	Fentanyl, 3	Oxycodone, 80	Fentanyl, 1	Fentanyl, 0.5
Time since OIC diagnosis, mo	<1	<1	<1	<1	<1	<1	<1	<1	<1	<1
Use of PAMORA (naldemedine)	Yes	No	Yes	Yes	Yes	Yes	No	Yes	Yes	No

Eight of ten patients showed improvement in constipation symptoms. The mean CAS score decreased by −2.8 points (SD: 3.0; p = 0.012) after six sessions of moxibustion, with the benefit sustained at 4-week follow-up (−2.5, SD: 2.7; p = 0.022) (Table 3). Spontaneous bowel function improved during the treatment period. The mean time to first spontaneous bowel movement after initiation of moxibustion was 0.9 days. The mean number of spontaneous bowel movements per week increased significantly from 1.6 at baseline to 4.4 posttreatment (mean change + 2.8, SD: 1.9; p = 0.003), with the effect partially maintained at follow-up (3.9; mean change + 2.3, SD: 1.8; p = 0.027). In parallel with these improvements, all patients reduced their laxative use during the treatment period. Stool consistency also improved, with the proportion of patients achieving normal stool form (BSFS types 3–4) increasing from 20.0% at baseline to 60.0% posttreatment, although this decreased to 30.0% at follow-up (Table 3). Several patients achieved normalization of stool consistency, although some continued to report loose or small-volume stools (types 6–7).

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Table 3.

Primary and Secondary Outcomes

Outcome measures	Pre	Post	Follow-up	Pre–post			Pre-follow-up
				Difference	SD	p Value	Difference	SD	p Value
CAS, mean (SD)	8.6	5.8	6.1	−2.8	3.0	0.012	−2.5	2.7	0.022
ESAS, mean (SD)
Pain	3.3	2.1	2.4	−1.2	2.6	0.120	−0.9	3.2	0.232
Fatigue	3.0	3.1	2.5	0.1	2.5	0.939	−0.5	1.6	0.589
Drowsiness	3.2	2.4	2.3	−0.8	2.7	0.564	−0.9	3.1	0.461
Nausea	1.2	1.6	1.3	0.4	3.1	0.656	0.1	2.3	0.655
Appetite	3.2	3.2	4.0	0.0	2.0	0.728	0.8	2.3	0.757
Shortness of breath	0.9	1.0	2.2	0.1	1.4	0.935	1.3	1.7	0.202
Depression	1.5	2.7	3.1	1.2	1.1	0.129	1.6	1.1	0.076
Anxiety	1.8	2.9	3.0	1.1	1.4	0.211	1.2	1.6	0.216
Overall condition	3.7	2.6	3.6	−1.1	1.8	0.051	−0.1	2.0	0.692
Time to first spontaneous bowel movement, days	0.9
Mean weekly spontaneous bowel movements (SBMs), mean (SD)	1.6	4.4	3.9	2.8	1.9	0.003	2.3	1.8	0.027
Stool consistency (BSFS types 3–4), n (%)	2/10 (20.0)	6/10 (60.0)	3/10 (30.0)

Clinically meaningful difference: 1.0 or greater, p < 0.05, repeated measurement dispersion analysis, Wilcoxon test.

CAS, Constipation assessment scale; ESAS, Edmonton symptom assessment scale; SBMs, spontaneous bowel movement; BSFS, Bristol Stool Form Scale.

During the short follow-up period, constipation symptoms did not uniformly recur, although longer-term outcomes could not be assessed.

Regarding general symptoms, ESAS-r-J indicated a mean improvement of −1.2 (SD: 2.6) in pain after treatment. Other physical symptoms showed minimal changes (mean change <1.0). Psychological distress scores showed a small increase (+1.2, SD: 1.1), indicating that emotional burden persisted despite stable pain control.

Discussion

This case series suggests that moxibustion may contribute to alleviation of OIC symptoms in patients with advanced cancer. In addition to improvements in constipation symptoms and reduced laxative use, the absence of treatment-related adverse events highlights its feasibility and safety in routine clinical care.

The potential mechanisms of action of moxibustion include stimulation of intestinal peristalsis, enhancement of local blood flow, and modulation of the autonomic nervous system through thermal stimulation at acupoints. ²¹ The clinical improvements observed in this study are consistent with these proposed mechanisms. Notably, spontaneous bowel movements occurred early after initiation of moxibustion, with a mean time to first bowel movement of less than one day. This finding suggests a rapid onset of effect, which may be clinically meaningful for patients experiencing distressing constipation. Nevertheless, stool quality remained a challenge: while some patients achieved normalization, others experienced loose or small-volume stools, likely reflecting the complexity of OIC and possible overflow constipation.³ This may also explain the observed alternation between constipation and diarrhea, resulting from intermittent leakage of liquid stool around impacted feces. The decline in normalization rates at follow-up may suggest that the effects of moxibustion are time-limited, and repeated or maintenance sessions may be required to sustain these benefits, which should be explored in future studies.

The integration of complementary therapies with pharmacological interventions plays an important role in OIC management. Acupuncture and moxibustion have long been used for pain and functional constipation, and recent attention has focused on their role in OIC. Evidence from randomized trials and meta-analyses suggests that these interventions improve stool frequency, abdominal symptoms, and QOL.^11–16 Our findings extend this evidence by demonstrating that a standardized moxibustion protocol can be safely implemented in a real-world palliative care setting. In addition, all patients were able to reduce their laxative use during the treatment period, suggesting that moxibustion may help decrease reliance on pharmacologic interventions. This is particularly relevant in palliative care, where minimizing medication burden is an important clinical goal.

Regarding general symptoms, the ESAS-r-J showed a modest improvement in pain scores, while other physical symptoms demonstrated minimal changes. Psychological distress scores showed a small increase, indicating that emotional burden persisted despite stable pain control. This finding likely reflects the multifactorial nature of psychological distress in advanced cancer, including disease progression, prognostic awareness, and psychosocial stressors that may not improve in parallel with physical symptom control.

When introducing nonpharmacological interventions, it is essential to consider patients’ needs, treatment preferences, and the balance with existing therapies. Deng emphasized that although integrative therapies can improve QOL, their application requires careful consideration of evidence quality, potential risks, and financial burden. ²² These perspectives are crucial for integrating acupuncture and moxibustion into palliative care. Although moxibustion was readily available and feasible within our hospital setting in Japan, its availability and insurance coverage vary across countries and health care systems. Therefore, issues related to access, cost, and equity should be considered when interpreting the generalizability of these findings to other settings.

This study has limitations, including its small sample size, lack of a control group, and reliance on subjective measures. However, its strengths include prospective design, standardized intervention protocol, and detailed safety monitoring. These features support the reliability of our observations.

In summary, moxibustion appears to be a feasible, safe, and potentially useful complementary intervention for OIC in advanced cancer. While larger controlled trials are needed, the present findings suggest that clinicians may consider moxibustion as a supportive option when conventional treatments are insufficient.

Conclusion

This prospective case series suggests that moxibustion may be a complementary option for managing OIC in patients with advanced cancer. Further controlled studies are warranted to confirm efficacy and to define the optimal treatment protocol.

Authors’ Contributions

K.K. and A.M. conceived the study. K.K. collected and analyzed the data and drafted the article. A.M. supervised the clinical management, contributed to patient recruitment and data acquisition. N.R.N. contributed to study design and interpretation and assisted in article editing. T.H. provided academic supervision and contributed to the interpretation of results. A.H. provided guidance on research design and critically reviewed the article. All authors critically revised and approved the final version of the article.

Ethics Approval and Consent to Participate

The study was conducted according to the Declaration of Helsinki and approved by the Ethics Committee of Kagawa University School of Medicine (approval no.: 2021–119; approval date: November 8, 2021). Written informed consent was obtained from all participants. All patient information was fully anonymized prior to analysis and reporting.

Consent for Publication

Written informed consent for publication of anonymized clinical data was obtained from all participants. All patient information was fully anonymized prior to analysis and reporting.

Use of Artificial Intelligence

No generative artificial intelligence tools were used to create, analyze, or interpret the data in this study.

AI-based tools were used only for language editing after the scientific content was finalized, and all authors reviewed and approved the final article.