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The clinical use of Kampo medicines (traditional Japanese herbal treatments) for controlling cancer patients’ symptoms in Japan: a national cross-sectional survey

  • Satoru Iwase1,
  • Takuhiro Yamaguchi2,
  • Tempei Miyaji3Email author,
  • Kiyoshi Terawaki4,
  • Akio Inui5 and
  • Yasuhito Uezono4
BMC Complementary and Alternative MedicineBMC series ¿ open, inclusive and trusted201212:222

DOI: 10.1186/1472-6882-12-222

Received: 15 May 2012

Accepted: 13 November 2012

Published: 20 November 2012

Abstract

Background

Kampo medicines are traditional Japanese medicines produced from medicinal plants and herbs. Even though the efficacy of Kampo medicines for controlling cancer-related symptoms is being reported, their actual nationwide clinical use has not been comprehensively investigated. We aimed to investigate physicians’ recognition of Kampo medicines and their clinical use for cancer patients in the field of palliative care.

Methods

A cross-sectional self-administered anonymous questionnaire was distributed to 549 physicians working in palliative care teams at 388 core cancer treatment hospitals and 161 certified medical institutions that have palliative care units (PCUs).

Results

Valid responses were obtained from 311 physicians (response rate, 56.7%) who were evenly distributed throughout the country without significant geographical biases. Kampo medicines were prescribed for controlling cancer-related symptoms by 64.3% of the physicians. The symptoms treated with Kampo medicines were numbness/hypoesthesia (n = 99, 49.5%), constipation (n = 76, 38.0%), anorexia/weight loss (n = 72, 36%), muscle cramps (n = 71, 35.5%) and languor/fatigue (n = 64, 32.0%). Regarding open issues about prescription, 60.7% (n = 173) of the physicians raised the issue that the dosage forms need to be better devised.

Conclusions

To increase the clinical use of Kampo medicines, more evidence from clinical studies is necessary. In addition, their mechanisms of action should be clarified through laboratory studies.

Keywords

Kampo Kampo medicine Palliative care Symptom management Survey

Background

History of kampo medicine

Kampo medicines are traditional Japanese medicines produced from medicinal plants and herbs. Kampo originates from China and has been adapted to the Japanese culture[1]. Chinese herbal medicine was imported to Japan in 552 AD, after which it was uniquely developed into Japanese Kampo[2]. Traditional Chinese Medicine is deeply philosophical and ideological, while Japanese Kampo tends to be more practical and simplified, and relies little on Taoist or other Chinese philosophy[2].

Kampo medicines are currently of great interest to palliative care physicians because of their potential to alleviate the adverse side effects of cancer treatment and improve patients’ quality of life.

Use of Kampo and CAM in Japan

In the past few decades, Kampo has reintegrated into modern medical practice, accompanied by a scientific reevaluation and critical examination of its relevance in conventional medicine[2, 3]. Kampo has been used in addition or alternatively to conventional medicines[4]. Currently more than 70% of Japanese physicians prescribe Kampo medicines in daily clinical practices[5]. Previous survey research has reported that 76% of the general population in Japan and 50% of outpatients in Tokyo have used some form of CAM and that 10% of the general population and 19% of outpatients in Tokyo had used Kampo medicine prescribed by physicians within the last 12 months[6, 7]. In addition, the prevalence of use of CAM by cancer patients was 44.6% in Japan[8]. Internationally, the estimates of CAM use are higher in East Asia and highest in Japan compared to the USA and European countries[9, 10]. CAM is often used in palliative care settings where the goal is not cure but rather improvement in QOL[10].

To date, the Ministry of Health, Labour and Welfare (MHLW) has approved the use of 148 Kampo medicines, and the prescription of Kampo medicines is within the national health insurance system[3, 11]. Although Kampo can be seen as orthodox from a historical Japanese perspective, it tends to be classified as Complementary and Alternative Medicine (CAM) according to Western conventions. The main reason for this is the lack of scientific evidence of its efficacy and the limited knowledge and spread of this therapy in other regions, especially outside of East Asia.

However, clinical studies of Kampo have been conducted in Japan, and its efficacy has been reported in research papers. For example, a randomized control trial demonstrated that the Kampo medicine Rikkunshito exerted greater effects in alleviating gastrointestinal symptoms than cisapride (a gastroprokinetic agent)[12]. The efficacy of Rikkunshito against non-ulcer dyspepsia (NUD)[13, 14], gastrointestinal symptoms after gastrectomy (surgical NUD)[15], functional dyspepsia[16, 17], and nausea and vomiting caused by selective serotonin reuptake inhibitors[18] has also been reported. Also, the Japanese Society for Oriental Medicine has compiled comprehensive data on randomized controlled trials of Kampo medicine in Japan, published as “Evidence Reports of Kampo Treatment” (EKAT)[19]. In addition to clinical trials, the potential mechanisms of action of Kampo medicines are also starting to be reported[20].

As described above, there is increasing evidence of the efficacy of Kampo medicines and increasing attention has been given to their clinical application. However, there has been no comprehensive investigation of the use of Kampo medicines in cancer treatment. Therefore, we conducted a nationwide survey of the current use of Kampo medicines for cancer-related treatment and of physicians’ attitudes toward using Kampo medicines in Japan.

Methods

Study sample and data collection

The survey was carried out between January and March of 2011, by mailing a self-administered anonymous questionnaire to 549 palliative care physicians who administer chemotherapy to cancer patients or who are involved in their terminal care. The palliative care teams in 388 core cancer treatment hospitals and 161 palliative care units (PCUs) within medical institutions were selected because they represent palliative care practice in Japan. This included all core cancer treatment hospitals and PCUs in Japan as of February 2011. Core cancer treatment hospitals are the medical facilities specified by the MHLW to provide high-quality expert care for cancer patients. These facilities are established within each prefecture in Japan, according to the principles set forth in the Cancer Control Act promulgated in April 2007. The contact information of subjects was obtained from a web site of the Cancer Control Information Center, National Cancer Center[21].

We did not specifically include general internists or surgeons who are not in charge of palliative care as subjects of the survey. This is because the certification system for the palliative care specialist is still immature in Japan and the attending physicians of palliative care teams and PCUs are often internists or surgeons.

Questionnaire development

An eight-page, 18-item questionnaire was designed in Japanese. It covered four categories: (1) status of cancer treatment and use of Kampo medicines, (2) cancer cachexia and utilization of Kampo medicines (data not shown), (3) adverse side effects of anti-cancer drugs and utilization of Kampo medicines, and (4) background variables. Although the questionnaire was not formally validated, the questionnaire and its items were designed and formulated based upon the expert opinions of specialists from palliative care, medical oncology, Kampo medicine, and biological statistics, and also from literature reviews. It was finalized after testing several samples.

Ethical considerations

We conducted this research in compliance with the Helsinki Declaration. We had requested an ethical review of this research from the ethical review committee of the National Cancer Center prior to commencement. However, since this research involves neither patients’ data nor intervention, the committee judged that this research should not be subjected to any Japanese medical research guidelines. Accordingly, the research was exempt from the requirement for formal ethical approval.

To ensure that informed consent was obtained, the questionnaire was sent to the physicians with a leaflet explaining the survey’s objectives and that (1) each subject was free to decide whether or not to answer the questions; (2) the collected data will be processed and analyzed anonymously; and (3) the data will be securely archived by the Research Secretariat. Consent was implied through the return of a completed questionnaire.

Data analysis

The collected data were entered into an electronic database and analyzed using SPSS (IBM, New York, USA). Chi-squared tests (p value < 0.050) were conducted to compare the frequency distributions of two cross-tabulations. The first was physicians in the palliative care teams at the core cancer treatment hospitals compared with physicians in the PCUs. The second was the palliative care specialists certified by the Japan Society of Palliative Medicine (JSPM) compared with non-specialists.

Results and discussion

Of the 549 questionnaires distributed, 311 valid responses were collected for analysis (response rate, 56.7%). Responses were obtained from 226 physicians (response rate, 58.2%) at core cancer treatment hospitals (palliative care team physicians) and 79 physicians (response rate, 49.1%) from PCUs (PCU physicians). With the moderate rate of valid responses (56.7%), the respondents were well-distributed throughout the country, without significant geographical biases. Table1 shows the response rates and the respondents’ background characteristics. Two hundred thirty seven respondents (77.9%) were aged between 40 and 59 years. Two hundred seventy three respondents (90.1%) were male, and 128 respondents (41.2%) were JSPM-authorized palliative care specialists (including provisional medical advisors).
Table 1

Respondents’ background characteristics

Respondents (n = 311)

  

Average ± SD

Minimum value

Maximum value

  

Age

  

49 ± 8

28

75

  

Years of experience

  

23 ± 8

4

50

  
   

Responses

%

   

Institution (n = 549) *

       

 Core cancer treatment hospital (n = 388)

  

226

58.2

   

 Palliative Care Unit in medical institution (n = 161)

 

79

49.1

   
   

n

%

   

Age group

       

 20–29 years

  

1

0.3

   

 30–39 years

  

39

12.8

   

 40–49 years

  

119

39.1

   

 50–59 years

  

118

38.8

   

 ≥ 60 years

  

27

8.9

   

Sex

       

 Male

  

273

90.1

   

 Female

  

30

9.9

   

Palliative Care Specialists certified by JSPM**

      

 Specialists (including provisional medical advisors)

 

128

41.2

   

 Non-specialists

  

183

58.8

   

Region***

Hokkaido–Tohoku

Kanto

Chubu

Kinki

Chugoku

Shikoku

Kyushu–Okinawa

 Number of questionnaires distributed

79

116

92

91

47

27

97

 Number of responses

26

43

41

33

25

11

37

 Response rate (%)

32.9

37.1

44.6

36.3

53.2

40.7

38.1

*Six responses had missing institution data, and ***95 responses had missing region data.

** JSPM: Japan Society for Palliative Medicine.

Difficult to treat cancer-related symptoms

Physicians were asked to identify which of the 23 common cancer-related symptoms that they find difficult to treat (Table2). More than 50% of the physicians identified numbness/hypoesthesia (n = 240, 77.2%), languor/fatigue (n = 225, 72.3%), delirium (N = 170, 54.7%), and taste alteration (n = 166, 53.4%). In comparison with the PCU physicians, more palliative care team physicians identified taste alteration (p = 0.029), nausea/vomiting (during chemotherapy) (p = 0.000), and constipation (caused by opioid use) (p = 0.038). More of the PCU physicians, on the other hand, reported having difficulty treating adjustment disorder (p = 0.014). In addition, the symptoms of taste alteration (p = 0.050), dysphagia/deglutition disorder (p = 0.036) and muscle weakness (p = 0.047) were identified as being difficult to treat more often by the palliative care specialists than the non-specialists.
Table 2

Difficult to treat cancer-related symptoms identified by physicians

Symptoms

All physicians (n = 311)

Palliative care teams (n = 226)

PCUs (n = 79)

p-value

Specialists (n = 128)

Non-specialists (n = 183)

p-value

frequency

%

frequency

%

frequency

%

frequency

%

frequency

%

Numbness/Hypesthesia

240

77.2

180

79.6

55

69.6

0.165

99

77.3

141

77.0

1.000

Languor/Fatigue

225

72.3

161

71.2

61

77.2

0.276

99

77.3

126

68.9

0.122

Delirium

170

54.7

119

52.7

48

60.8

0.447

73

57.0

97

53.0

0.490

Taste alteration

166

53.4

124

54.9

42

53.2

0.029

77

60.2

89

48.6

0.050

Edema (Local edema/Anasarca)

150

48.2

109

48.2

39

49.4

0.821

59

46.1

91

49.7

0.565

Pain

146

46.9

113

50.0

31

39.2

0.226

55

43.0

91

49.7

0.250

Anorexia/Weight loss

140

45.0

109

48.2

30

38.0

0.108

64

50.0

76

41.5

0.165

Abdominal discomfort

131

42.1

98

43.4

31

39.2

0.735

55

43.0

76

41.5

0.816

Stomatitis/Xerostomia

122

39.2

89

39.4

33

41.8

0.141

54

42.2

68

37.2

0.409

Depression

116

37.3

86

38.1

30

38.0

0.175

41

32.0

75

41.0

0.122

Adjustment disorder

113

36.3

73

32.3

39

49.4

0.014

47

36.7

66

36.1

1.000

Dyspnea/Breathlessness

113

36.3

77

34.1

35

44.3

0.162

48

37.5

65

35.5

0.811

Nausea/Vomiting (other)

101

32.5

75

33.2

24

30.4

0.893

38

29.7

63

34.4

0.392

Dysphagia/Deglutition disorder

100

32.2

68

30.1

31

39.2

0.281

50

39.1

50

27.3

0.036

Sleep disorder/Insomnia

93

29.9

69

30.5

23

29.1

0.796

42

32.8

51

27.9

0.379

Constipation (caused by opioid use)

84

27.0

69

30.5

15

19.0

0.038

34

26.6

50

27.3

0.898

Nausea/Vomiting (during chemotherapy)

76

24.4

71

31.4

5

6.3

0.000

27

21.1

49

26.8

0.284

Muscle weakness

65

20.9

46

20.4

19

24.1

0.346

34

26.6

31

16.9

0.047

Nausea/Vomiting (caused by opioid use)

61

19.6

51

22.6

10

12.7

0.690

24

18.8

37

20.2

0.774

Constipation (not caused by opioid use)

59

19.0

47

20.8

11

13.9

0.377

28

21.9

31

16.9

0.305

Muscle cramp

42

13.5

31

13.7

11

13.9

0.741

23

18.0

19

10.4

0.064

Diarrhea

40

12.9

34

15.0

6

7.6

0.136

16

12.5

24

13.1

1.000

Anemia

29

9.3

24

10.6

5

6.3

0.344

16

12.5

13

7.1

0.177

Others

11

3.5

6

2.7

5

6.3

0.325

4

3.1

7

3.8

0.770

Multiple answers allowed, p-value based on Chi-square test.

Numbness is a neuropathic symptom that frequently occurs as an adverse side effect of chemotherapy. It has been reported to account for 58% of all neurological symptoms experienced by cancer patients[22]. Fatigue is the most common cancer symptom[23], and was reported by 66% of patients in a previous study[22]. The prevalence of delirium is 25–40% (85–88% in the terminal stage of cancer)[2426], and the prevalence of taste alteration is 36–75% among patients receiving chemotherapy[27]. Thus, it was shown in the present survey that the symptoms palliative care physicians have difficulty managing in Japan are those frequently seen in cancer patients.

We also found that the palliative care team physicians confront taste alteration (p = 0.029), nausea/vomiting during chemotherapy (p = 0.000) and constipation during opioid use (0.038) more often than the PCU physicians (Table2). These facts suggest that the palliative care teams are often in charge of patients receiving chemotherapy, while PCUs are more frequently dealing with psychiatric symptoms than the adverse side effects of chemotherapy.

Prescription of Kampo medicines

Kampo medicines were being prescribed by 64.3% (n = 200) of the physicians to alleviate the cancer patients’ symptoms. Kampo medicines were prescribed to control numbness/hypoesthesia (n = 99, 49.5%), constipation (not caused by opioid use) (n = 76, 38%), anorexia/weight loss (n = 72, 36%), muscle cramps (n = 71, 35.5%), and languor/fatigue (n = 64, 32%) by more than 30% of the physicians (Table3). The palliative care team physicians prescribed Kampo medicines for numbness/hypoesthesia (p = 0.000), anorexia/weight loss (p = 0.046), pain (p = 0.020), and nausea/vomiting during chemotherapy (p = 0.016), more frequently than the PCU physicians. This difference may arise because the palliative care teams more often examine patients who are under chemotherapy than the PCUs, and thus they pay more attention than the PCUs to the necessity of controlling the adverse side effects of chemotherapy. Also, PCU patients have more difficulty taking Kampo medicines than the general hospital patients under the palliative care teams. The frequency of prescribing Kampo medicines did not vary significantly across the symptoms between the palliative care specialists and non-specialists.
Table 3

Symptoms for which Kampo medicines were prescribed

Symptoms

All physicians (n = 200)

Palliative care teams (n = 149)

PCUs (n = 46)

p-value

frequency

%

frequency

%

frequency

%

Numbness/Hypesthesia

99

49.5

86

57.7

12

26.1

0.000

Constipation (not caused by opioid use)

76

38

56

37.6

20

43.5

0.182

Anorexia/Weight loss

72

36

60

40.3

12

26.1

0.046

Muscle cramp

71

35.5

54

36.2

17

37.0

0.279

Languor/Fatigue

64

32

49

32.9

14

30.4

0.818

Constipation (caused by opioid use)

48

24

37

24.8

11

23.9

0.490

Abdominal discomfort

46

23

29

19.5

16

34.8

0.088

Diarrhea

45

22.5

39

26.2

5

10.9

0.090

Delirium

40

20

27

18.1

13

28.3

0.155

Pain

38

19

35

23.5

3

6.5

0.020

Edema (Local edema/Anasarca)

31

15.5

25

16.8

6

13.0

0.546

Nausea/Vomiting (other)

27

13.5

22

14.8

5

10.9

0.566

Nausea/Vomiting (during chemotherapy)

22

11

22

14.8

0

0.0

0.016

Stomatitis/Xerostomia

21

10.5

19

12.8

2

4.3

0.216

Taste alteration

20

10

17

11.4

3

6.5

0.409

Depression

20

10

17

11.4

3

6.5

0.409

Nausea/Vomiting (caused by opioid use)

17

8.5

16

10.7

1

2.2

0.129

Adjustment disorder

15

7.5

12

8.1

3

6.5

0.846

Sleep disorder/Insomnia

14

7

10

6.7

4

8.7

0.823

Others

13

6.5

6

4.0

6

13.0

0.055

Anemia

11

5.5

9

6.0

2

4.3

0.805

Dysphagia/Deglutition disorder

10

5

9

6.0

1

2.2

0.581

Dyspnea/Breathlessness

6

3

5

3.4

1

2.2

1.000

Muscle weakness

3

1.5

3

2.0

0

0.0

0.614

Multiple answers allowed, p-value based on Chai-square test.

Reasons for prescription

More than 60% of the physicians prescribed Kampo medicines for the following reasons: ‘the drug therapy options are greater’ (n = 144, 72%), ‘ineffectiveness of other treatments’ (n = 129, 64.5%), and ‘unavailability of other appropriate treatments’ (n = 127, 63.5%). Although ‘patient demand’ was the least frequent reason (n = 46, 23%), palliative care specialists were more attentive to patients’ demands than non-specialists (n = 28, 37.3%, p = 0.000).

Variety and frequency of prescriptions

Eight Kampo medicines were selected from the literature reviews to investigate frequency of prescription. Table4 shows the composition of each Kampo medicine[2830].Daikenchuto was the most frequently prescribed (n = 140, 70%) among eight major Kampo medicines (Table5). This is probably because the efficacy of Daikenchuto for the treatment of gastrointestinal symptoms is currently being tested in clinical trials in Japan and the United States. A tolerability and efficacy phase II study of Daikenchuto for the treatment of postoperative ileus has been already completed in the United States[31]. This might encourage its prescription by physicians. The palliative care team physicans prescribed Goshajinkigan (p = 0.000), Rikkunshito (p = 0.001), Hochuekkito (p = 0.011), Juzentaihoto (p = 0.001), and Hangeshashinto (p = 0.000) more frequently than PCU physicians, while there were no significant differences in the medicines prescribed between the palliative care specialists and non-specialists.
Table 4

Composition of Kampo medicines

Kampo Medicine

Ingredients (crude drugs)

Hangeshashinto

Pinelliae Tuber

Scutellariae Radix

Zingiberis Processum Rhizoma

Glycyrrhizae Radix

Zizyphi Fructus

Ginseng Radix

Coptidis Rhizoma

   

Hochuekkito

Astragali Radix

Atractylodis lanceae Rhizoma

Ginseng Radix

Angelicae Radix

Bupleuri Radix

Zizyphi Fructus

Aurantii Nobilis Pericarpium

Glycyrrhizae Radix

Cimicifugae Rhizoma

Zingiberis Rhizoma

Rikkunshito

Atractylodis lanceae Rhizoma

Ginseng Radix

Pinelliae Tuber

Poria

Zizyphi Fructus

Aurantii Nobilis Pericarpium

Glycyrrhizae Radix

Zingiberis Rhizoma

  

Juzentaihoto

Astragali Radix

Cinnamomi Cortex

Rehmanniae Radix

Paeoniae Radix

Cnidii Rhizoma

Atractylodis lanceae Rhizoma

Angelicae Radix

Ginseng Radix

Poria

Glycyrrhizae Radix

Yokukansan

Atractylodis lanceae Rhizoma

Poria

Cnidii Rhizoma

Uncariae Uncis cum Ramulus

Angelicae Radix

Bupleuri Radix

Glycyrrhizae Radix

   

Shakuyakukanzoto

Glycyrrhizae Radix

Paeoniae Radix

        

Daikenchuto

Zingiberis Processum Rhizoma

Ginseng Radix

Zanthoxyli Fructus

       

Goshajinkigan

Rehmanniae Radix

Achyranthis Radix

Corni Fructus

Dioscoreae Rhizoma

Plantaginis Semen

Alismatis Rhizoma

Poria

Moutan Cortex

Cinnamomi Cortex

Processi Aconiti Radix

Ingredients of each Kampo medicine were based on the package inserts of Tsumura products[28].

Scientific names of ingredients were based on Metabolomics.jp[29] and The Japanese Pharmacopeia Fifteenth edition[30].

Table 5

The Kampo medicines prescribed by the physicians

Kampo medicine

All physicians (n = 200)

Palliative care teams (n = 149)

PCUs (n = 46)

p-value

 

frequency

%

frequency

%

frequency

%

Daikenchuto

140

70.0

109

73.2

29

63.0

0.124

Goshajinkigan

100

50.0

89

59.7

11

23.9

0.000

Rikkunshito

97

48.5

82

55.0

15

32.6

0.001

Shakuyakukanzoto

96

48.0

76

51.0

20

43.5

0.069

Hochuekkito

90

45.0

76

51.0

13

28.3

0.011

Juzentaihoto

84

42.0

73

49.0

11

23.9

0.001

Yokukansan

61

30.5

45

30.2

16

34.8

0.253

Hangeshashinto

54

27.0

51

34.2

3

6.5

0.000

Others

24

12.0

20

13.4

4

8.7

0.457

Multiple answers allowed, p-value based on Chi-square test.

Physician-recognized effectiveness

We investigated the physician-recognized effectiveness of eight Kampo medicines. Two symptoms from each Kampo medicine’s package insert were listed and the physicians were asked to indicate whether they believed the medicine effectively treated them (Table6). More than 50% of the physicians recognized the effectiveness of Hangeshashinto against diarrhea caused by chemotherapy (n = 31, 53.4%), of Hochuekkito and Juzentaihoto against fatigue (n = 54, 56.3% and n = 50, 56.8% respectively), of Rikkunshito against anorexia (n = 46, 50%), of Yokukansan against delirium (n = 38, 63.3%), of Shakuyakukanzoto against leg cramps (n = 79, 82.3%), and of Daikenchuto against ileus (n = 101, 78.9%) and opioid-caused constipation and abdominal pain (n = 62, 53.9%). There was no significant difference in the medicines recognized as effective between the palliative care team and PCU physicians, while the palliative care specialists seemed to be more aware of the effectiveness of Rikkunshito against nausea than non-specialists (p = 0.012) (Table6). These results suggest that there is consensus among palliative care physicians regarding the effectiveness of particular Kampo medicines against particular symptoms.
Table 6

Physician-recognized effectiveness of Kampo medicines

Kampo medicine

Symptoms

Recognized as effective

All physicians

Specialists

Non-specialists

p-value

frequency/total

%

frequency/total

%

frequency/total

%

 

Hangeshashinto

Diarrhea caused by chemotherapy

31/58

53.4

10/22

45.5

21/36

58.3

0.420

 

Nausea

10/45

22.2

3/21

14.3

7/24

29.2

0.296

Hochuekkito

Anorexia

44/90

48.9

14/36

38.9

30/54

55.6

0.137

 

Fatigue

54/96

56.3

19/39

48.7

35/57

61.4

0.295

Rikkunshito

Nausea

36/82

43.9

9/34

26.5

27/48

56.3

0.012

 

Anorexia

46/92

50.0

18/40

45.0

28/52

53.8

0.528

Juzentaihoto

Fatigue

50/88

56.8

17/33

51.5

33/55

60.0

0.508

 

AE caused by chemotherapy or radiotherapy

27/58

46.6

7/22

31.8

20/36

55.6

0.106

Yokukansan

Delirium

38/60

63.3

18/26

69.2

20/34

58.8

0.433

 

Anxiety

15/50

30.0

6/23

26.1

9/27

33.3

0.758

Shakuyakukanzoto

Leg cramps

79/96

82.3

36/43

83.7

43/53

81.1

0.794

 

Abdominal pain

20/57

35.1

11/25

44.0

9/32

28.1

0.268

Daikenchuto

Ileus

101/128

78.9

35/48

72.9

66/80

82.5

0.263

 

Opioid-caused constipation and abdominal pain

62/115

53.9

22/47

46.8

40/68

58.8

0.254

Goshajinkigan

Numbness of hands and feet

47/107

43.9

18/39

46.2

29/68

42.6

0.840

 

Nocturia

13/60

21.7

4/26

15.4

9/34

26.5

0.358

Multiple answers allowed, p-value based on Chi-square test.

Prescription considerations

In the questionnaire, the physicians were asked, “What are the important considerations when selecting a Kampo medicine for prescription?”. More than 80% of the physicians recognized the importance of ‘symptom-alleviating effects (alleviation of adverse side effects) (n = 173, 93%)’, ‘alleviation of symptoms that reduce QOL in the terminal stage of cancer’ (n = 162, 87.6%), ‘low incidence of adverse side effects’ (n = 157, 84.9%) and ‘easy to combine with other drugs’ (n = 149, 80.5%). The palliative care specialists tended to place more importance than the non-specialists on ‘patient demand’ (p = 0.050).

Open issues for prescription

The questionnaire also asked the physicians to identify any open issues regarding the prescription of Kampo medicines (Table7), revealing that 60.7% (n = 173) of the physicians were concerned that the dose and dosage forms need to be better devised for simpler administration. Kampo medicines are commonly prepared in granule form or as decoctions, and their administration method is nauseating for some patients. This issue may be related to the observation that “patient demand” was chosen least frequently as the reason for prescription. In the clinical field of palliative care, Kampo medicines are often mixed in a jelly for patients who have dysphagia. For future prescriptions, the administration forms need to be better devised from an adherence perspective. The second most frequently identified issue was the lack of scientific evidence for their efficacy, with 38.2% (n = 109) of the physicians highlighting the absence of evidence from placebo-controlled trails. Watanabe et al.[3] recently reported a summary of 135 peer-reviewed Kampo trials published between 1988 and 2007. According to their report, 106 trials were RCTs, and only 22 were placebo-controlled trials. In two-thirds of the trials, the sample size was less than 100 patients, and only 35 trials were published in English and the rest were in Japanese. Watanabe et al.[3] concluded that the overall quality of the research was low.
Table 7

Open issues about prescribing Kampo medicine (n = 285)

Issue

frequency

%

The dose and dosage forms need to be better devised for simpler application

173

60.7

No evidence of efficacy from placebo-controlled studies

109

38.2

Action mechanism of Kampo medicine is not yet elucidated

97

34.0

No opportunity to learn about Kampo medicines

90

31.6

Relatively weak effect

79

27.7

Drug interaction is uncertain

66

23.2

Production of effect is slow

56

19.6

Others

25

8.8

There are no issues

12

4.2

Multiple answers allowed.

Conclusions

We conducted a nationwide survey of 311 physicians working in palliative care teams at core cancer treatment hospitals and PCUs within medical facilities. Kampo medicines were prescribed by a high proportion (n = 200, 64.3%) of the palliative care physicians and were expected to provide valid means of controlling the cancer patients’ symptoms or the adverse side effects of chemotherapy. Palliative care physicians appear to be aware of the effectiveness of Kampo medicines. However, they prescribe Kampo medicines only to a limited extent because of the lack of evidence for their efficacy. Hence, we believe that the collection of more evidence from clinical studies is desirable in Japan.

Abbreviations

MHLW: 

Ministry of health labour and welfare

CAM: 

Complementary and alternative medicine

PCUs: 

Palliative care units.

Declarations

Acknowledgments

This work was supported by Grants-in-Aid for the Third-term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare, Japan and the Foundation for Promotion of Cancer Research in Japan, as well as a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports Science and Technology of Japan.

Authors’ Affiliations

(1)
Department of Palliative Medicine, The University of Tokyo Hospital
(2)
Division of Biostatistics, Tohoku University Graduate School of Medicine
(3)
Interfaculty Initiative in Information Studies, The University of Tokyo
(4)
Division of Cancer Pathophysiology, National Cancer Center Research Institute
(5)
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences

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