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

  • Satoru Iwase1,

    Affiliated with

    • Takuhiro Yamaguchi2,

      Affiliated with

      • Tempei Miyaji3Email author,

        Affiliated with

        • Kiyoshi Terawaki4,

          Affiliated with

          • Akio Inui5 and

            Affiliated with

            • Yasuhito Uezono4

              Affiliated with

              BMC Complementary and Alternative MedicineThe official journal of the International Society for Complementary Medicine Research (ISCMR)201212:222

              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. Table 1 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 (Table 2). 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 (Table 2). 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 (Table 3). 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. Table 4 shows the composition of each Kampo medicine [2830].Daikenchuto was the most frequently prescribed (n = 140, 70%) among eight major Kampo medicines (Table 5). 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 (Table 6). 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) (Table 6). 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 (Table 7), 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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              © Iwase et al.; licensee BioMed Central Ltd. 2012

              This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.