Indian Journal of Research in Homeopathy

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 14  |  Issue : 3  |  Page : 189--199

Effects of pre-defined Homoeopathic medicines to mitigate adverse dermatological effects of radiotherapy and vomiting of chemotherapy in breast carcinoma: A randomised, double-blind, placebo-controlled, pilot trial in the context of usual care


Purnima Shukla1, Chaturbhuja Nayak1, Mirza Qaiser Baig2, Purak Misra3,  
1 Department of Homoeopathic Materia Medica, Homoeopathy University, Jaipur, Rajasthan, India
2 Department of Radiotherapy, BRD Medical College, Gorakhpur, Uttar Pradesh, India
3 Department of Minimal Access and General Surgery, ESIC Hospital, Okhla, New Delhi, India

Correspondence Address:
Dr. Purnima Shukla
Department of Homoeopathic Materia Medica, Homoeopathy University, Saipura, Sanganer, Jaipur, Rajasthan
India

Abstract

Background: Radiotherapy and chemotherapy are used in breast cancer, but they cause an array of adverse effects including dermatological changes and vomiting. Objective: The objective of the study was to examine whether Usual Care (UC) plus pre-defined homoeopathic remedies can produce different effect beyond UC plus placebo in dermatological adverse effects of radiotherapy and vomiting of chemotherapy in breast carcinoma. Methods: In this double-blind, randomised, placebo-controlled, parallel-arm trial, 88 females suffering from dermatological adverse effects due to radiotherapy (n = 41) or vomiting due to chemotherapy (n = 47) were randomised to receive either UC + Homoeopathy (verum; n = 44) or UC + Placebo (control; n = 44). The outcome measures were the number of responders showing any reduction of grades of Acute Radiation Morbidity Scoring Criteria (ARMSC) of the Radiation Therapy Oncology Group and Common Toxicity Criteria (CTC) for vomiting, measured at baseline and after 7 and 14 days. Relative Risk (RR) with 95% Confidence Intervals (CIs) was assessed; Chi-square tests were run to report P values. Results: A protocol-compliant sample (n = 80; 8 dropped out, verum: 4, control: 4) was analysed. The number of responders as per the ARMSC score after 7 days (11/18 vs. 1/19, RR = 3.3, 95% CI = 1.7–6.3, P = 0.001) and 14 days (16/18 vs. 1/19, RR = 9.4, 95% CI = 2.5–35.2, P < 0.001) was statistically significant, favouring verum over control. Similar results were obtained according to the CTC scoring after 7 days (15/22 vs. 2/21, RR = 3.3, 95% CI = 1.7–6.3, P < 0.001) and 14 days (21/22 vs. 4/21, RR = 15.1, 95% CI = 2.2–102.4, P < 0.001). Conclusion: Pre-identified homoeopathic medicines appeared superior to placebo, warranting further evaluation.



How to cite this article:
Shukla P, Nayak C, Baig MQ, Misra P. Effects of pre-defined Homoeopathic medicines to mitigate adverse dermatological effects of radiotherapy and vomiting of chemotherapy in breast carcinoma: A randomised, double-blind, placebo-controlled, pilot trial in the context of usual care.Indian J Res Homoeopathy 2020;14:189-199


How to cite this URL:
Shukla P, Nayak C, Baig MQ, Misra P. Effects of pre-defined Homoeopathic medicines to mitigate adverse dermatological effects of radiotherapy and vomiting of chemotherapy in breast carcinoma: A randomised, double-blind, placebo-controlled, pilot trial in the context of usual care. Indian J Res Homoeopathy [serial online] 2020 [cited 2020 Nov 27 ];14:189-199
Available from: https://www.ijrh.org/text.asp?2020/14/3/189/296245


Full Text



 Introduction



Breast cancer is the most common cancer in women both in the developed and less developed world, constituting about 22% of all female cancers. It is estimated that worldwide over 508,000 women died in 2011 due to breast cancer. Almost 50% of breast cancer cases and 58% of deaths occur in less developed countries. The incidence rates vary greatly worldwide from 19.3/100,000 women in eastern Africa to 89.7/100,000 women in western Europe. The lowest incidence rates are found in most African countries, but incidence rates are increasing in India also.[1] The incidence of breast cancer in India varies from as low as 5/100,000 females per year in rural areas to 30/100,000 females per year in urban areas. There is an impression of higher incidence of breast cancer in younger women in India as most hospital-based series report the median age of breast cancer patients to be a decade younger than that of Western series. However, this may be due to a combination of the population structure and inherent bias against referral, treatment and ascertainment of breast cancer in the elderly in India rather than a true reflection. The incidence of breast cancer increases with age, and this is true in India like rest of the world.[2] Standard breast cancer management strategies include surgery, radiotherapy, chemotherapy and biological and hormonal therapies. Surgery is the first line of treatment in all the cases, barring few inoperable advanced stage cases. It may be followed by chemotherapy or radiation therapy or both. Hormone receptor-positive cancers are often treated with hormone-blocking therapy; similarly monoclonal antibodies, or immune-modulating treatments, may be administered in certain cases of metastatic and other advanced stages of breast cancer.

The results of several studies indicated that conventional treatment based on surgery, radiotherapy and chemotherapy is often associated with adverse side effects.[3] The adverse effects of chemotherapy include bone marrow suppression, xerostomia, hair loss and thinning, infertility, skin and nail changes, nausea and vomiting, menopausal syndrome and cognitive impairment or dysfunction. The adverse effects of radiotherapy include radiodermatitis, telangiectasia, brachial plexopathy, nausea and fatigue.

Available literature reveals that in spite of the rapid strides in the field of oncology, a cost-effective, perfect and safe treatment to check the mortality rate is still a goal to be achieved. Many patients with cancer use complementary therapies, usually alongside orthodox treatments and Homoeopathy was in the top five most commonly used complementary therapies by cancer patients in seven out of 14 European countries by patients with cancer.[4],[5] A systematic review of 26 surveys from 13 countries reported that up to 64% of patients with cancer (average 31.4%) used complementary therapy at some stage of their illness. Recent studies suggest that additive homoeopathic medicines to standard therapies might be used to enhance survival [6] and improve the quality of life in cancer patients.[7] Homoeopathic literature also suggests a list of remedies to counter the adverse effects of chemotherapy and radiotherapy.[8],[9] Published researches provided promising evidences in favour of Homoeopathy to treat the adverse effects of conventional treatment in breast carcinoma.[10],[11] Some potential homoeopathic remedies for radiation exposure are Radium bromatum, X-ray, Uranium nitricum, Strontium carbonicum, Calendula officinalis, Cadmium sulphuratum, Cadmium iodatum and Ceanothus americanus. It is highly recommended to prescribe the remedies in proper dosage under skilled professional homoeopathic care.[12] In an open, randomised controlled trial (RCT), a homoeopathic complex was experimented against placebo to treat chemotherapy-induced nausea and vomiting in 55 patients, but no significant difference between the groups was elicited.[13] In a double-blind, RCT, non-individualised, standardised remedy comprising Cobaltum and Causticum was experimented against placebo in 82 patients for protection against radiation. Patients rated symptom severity score as 4.7 in Cobaltum patients, 5.4 in Causticum patients and 8.5 in placebo patients.[14] In a double-blind, RCT, a homoeopathic complex Traumeel S ® was tested against placebo in 32 children suffering from cancer, undergoing stem cell transplantation, and chemotherapy-induced stomatitis. Patients' rated symptom severity was significantly less in the Homoeopathy group than that in the placebo patients, thus favouring the use of Traumeel S ®.[15] However, in an international, multicentric, double-blind, randomised trial comparing Traumeel with placebo in patients aged 3–25 years undergoing myeloproliferative haematopoietic stem cell transfer, there was no statistically significant difference in mucositis in the Traumeel group compared with that of placebo group (P = 0.13). Although there was a trend towards less narcotic usage in the Traumeel patients, no beneficial effect from Traumeel was demonstrated for mucositis.[16] In another randomised trial, Calendula was compared against trolamine for the prevention of acute dermatitis during irradiation for breast cancer in 254 patients. The occurrence of acute dermatitis of Grade 2 or higher was statistically significantly lower (41% vs. 63%; P < 0.001) with the use of Calendula than with trolamine. Moreover, patients receiving Calendula had less frequent interruption of radiotherapy and significantly reduced radiation-induced pain. Thus, Calendula was found to be highly effective for the prevention of acute dermatitis of Grade 2 or higher and was recommended for patients undergoing post-operative irradiation for breast cancer.[10] In another double-blind, RCT, non-individualised, standardised remedy comprising Belladonna C7 and X-ray C15 was compared against placebo in 66 patients suffering from skin reactions after chemotherapy, but no significant differences were reported.[17] Daub et al. studied homoeopathic medicines for preventing adverse effect of venous cannulations in patients receiving chemotherapy.[13] Bourgois studied the role of homoeopathic medicines to protect venous function in women undergoing intravenous chemotherapy with no statistical significant difference.[18]

Thus, the overall scenario remains quite inconclusive about the effects of Homoeopathy in comparison with placebo in mitigating the dermatological adverse effects of radiotherapy and vomiting of chemotherapy in breast carcinoma. Hence, the investigators intended to examine whether usual care (UC) plus pre-defined homoeopathic medicines can produce significantly different treatment effect beyond UC plus placebo (UC + Pl) in the said conditions – both the conditions being very frequently encountered in the author's practice.

 Methods



Trial design

This prospective, double-blind, randomised, placebo-controlled, parallel-arm trial was conducted at the Department of Radiation Oncology, B. R. D. Medical College, Gorakhpur, Uttar Pradesh - 273013, India. The study protocol (unpublished) was submitted as a PhD synopsis of the corresponding author to the Homoeopathy University, Jaipur, Rajasthan, India, and was approved by the Institutional Ethics Committee of the University (Letter No. HU/2014/853/A; dated 20 September 2014) prior to initiation and enrolment; however, the trial was not registered in any trial registry due to some unavoidable circumstances. The proposed plan of work adhered to the ethical guidelines of the Declaration of Helsinki.[19]

Study duration

The trial started in February 2015 and was ended by January 2016.

Participants

Inclusion criteria were females suffering from the dermatological adverse effects of radiotherapy or vomiting due to chemotherapy of Grade I to III of both Acute Radiation Morbidity Scoring Criteria (ARMSC) and CTC scorings, respectively, age of 21–70 years and providing written consent to participate. Exclusion criteria were patients undergoing both radiotherapy and chemotherapy, ARMSC and CTC Grades IV; those unwilling to participate or having inability to comply with the trial requirements; those declined to provide informed consent; those with other uncontrolled systemic diseases and/or pathologies, psychiatric illness; those with ongoing use of homoeopathic medicines for any chronic diseases and those with drug or substance abuse and/or dependence.

Intervention

Experimental arm (verum)

The patients randomised to this arm received UC plus homoeopathic medicines from a list of nine pre-identified remedies (UC + Homoeopathy; verum: n = 44) – Apis mellifica, Arsenicum album, Belladonna, Cadmium sulphuricum, Carcinosinum, Ipecacuanha, Phosphorus, Radium bromide and X-ray [Table 1]. The shortlisting of the homoeopathic medicines was based on severity of symptoms in different grades and author's previous clinical experience (unpublished), better supported by the homoeopathic literature, Murphy's Materia Medica[8] and Synthesis Repertory.[9] The author's personal experience suggested that ARMSC Grades 1–3 can successfully be treated with Arsenicum album, Belladonna and Radium bromide, respectively, as the 1st-line remedies and, if failed, with Carcinosinum, Apis mellifica and X-ray and Carcinosinum subsequently. Similarly, CTC Grades 1–3 can be treated successfully with Ipecacuanha, Arsenicum album and Cadmium sulphuricum as the 1st-line remedies, respectively and, if failed, with Cadmium sulphuricum and Phosphorus, respectively. The medicines were prescribed in homoeopathic centesimal potencies (30c and 200c) to the patients experiencing side effects. Each dose consisted of four cane sugar globules medicated with a single drop of the indicated medicines. Repetition was 24, 12 or 8 hourly or even oftener, depending on the individual requirement of the case. Each dose was instructed to be taken orally on a clean tongue with an empty stomach. Duration of the therapy was 2 weeks. The homoeopathic medicines were obtained from Good Manufacturing Practice-certified pharmaceuticals. A single homoeopathic medicine from the list of pre-defined remedies was prescribed on each occasion taking into account the clinical presentation and consensus between two physicians. The individualised dose was based on physicians' judgement of susceptibility and consensus of two homoeopaths. As per usual homoeopathic prescribing procedures, if the first remedy was not helpful, the patient's symptoms were reassessed and a new remedy was prescribed. Each of the two prescribers in the study possessed master degree in Homoeopathy with more than 30 years of experience of practicing classical Homoeopathy. UC was administered and monitored all through by a conventionally trained and experienced radiotherapist as per the latest available guidelines for post-mastectomy radiotherapy [20] and chemotherapy [21] in personalised dosage catered to the patients' needs.{Table 1}

Control arm

Patients randomised to this arm received UC as above plus placebo (UC + Pl; control: n = 44). The placebo was indistinguishable from verum by appearance, smell and taste. Each placebo dose consisted of four cane sugar globules no. 30 moistened with a single drop of dispensing alcohol, instructed to be taken thrice a day orally on a clean tongue in an empty stomach. The duration of therapy was 2 weeks. Participants in the control arm were assessed similarly by the same two experienced homoeopaths as was done in the experimental arm. The 'placebo prescription' was similar to that for patients receiving actual medicines.

Usual care

It consisted of five types of chemotherapy drug regimens prescribed as per the personalised need of the enrolled patients – CMF, FAC followed by CMF, CMF alternated with EV, CMFVP and FEC (C = cyclophosphamide, M = methotrexate, F = 5-fluorouracil, A = adriamycin, E = epirubicin, V = vincristine and P = prednisone).

Outcomes

The outcome measure was the proportion of patients improved (i.e., n/N) as per the ARMSC and the Common Toxicity Criteria (CTC) version 3.0 for vomiting;[22],[23],[24] the assessment timeline was 7 days and 14 days. The ARMSC and CTC were created by the Radiation Therapy Oncology Group (RTOG) in 1985 and the US National Cancer Institute (NCI) in 1983 for the grading of radiotherapy- and chemotherapy-related effects, respectively. These scales are unpublished, yet widely used in clinical trials.[25] Assessment, both pre- and post-medication, was done by a conventionally trained and blinded radiotherapist. Responders were defined a priori as those patients showing any reduction of grades in the ARMSC or CTC scores over the defined time points. The ARMSC grading system was developed by the RTOG to classify radiotherapy effects. It identifies five grades – 0 (no reaction), 1 (faint erythema, dry desquamation, epilation and diminished sweating), 2 (moderate, brisk erythema, exudative dermatitis in plaques and moderate oedema), 3 (exudative dermatitis, besides cutaneous folds and intense oedema) and 4 (ulceration, haemorrhage and necrosis). However, only the dermatological component of this scale was used. The RTOG score has been widely employed for >25 years and is accepted and acknowledged by medical and nursing communities. The CTC scoring for vomiting was as follows – 0 (none), 1 (one episode in 24 h, intravenous fluids indicated <24 h), 2 (2–5 episodes in 24 h), 3 (more than 6 episodes in 24 h, intravenous fluids or total parenteral nutrition indicated >24 h) and 4 (life-threatening consequences).

Sample size

There has been no published placebo-controlled trial of similar design in the said condition. This precluded the formal calculation of standardised difference (effect size) and sample size. We assumed a medium effect size (w) of 0.3. Now keeping α = 0.05, minimum power (1 − β) recommendation = 0.80 and allocation ratio 1:1, to detect a significant difference between the two proportions of responder samples by goodness-of-fit Chi-square test through a 2 × 2 contingency table, the calculated sample size came to be 88.

Randomisation

SPSS software Statistical Package for the Social Sciences, version 20.0 (IBM Corp., IBM SPSS Statistics for Windows, Armonk, NY: USA)-generated random numbers were used to generate the random sequence in strict confidentiality by third parties, who were not allowed to influence the study in any way. The list was generated using restricted eight different blocks of size 10 and a single block of size 8 to maintain equal distribution between the groups and 1:1 ratio (8 × 10 = 80; 80 + 8 = 88; verum: 44, control: 44). The randomisation chart with allocated codes was available to the pharmacist for dispensing from coded vials.

Blinding

The participants, the investigators and the pharmacists were blinded to the allocated codes. Blinding was carried out by a third party in strict confidentiality to generate two sets of alike vials filled with either medicated or non-medicated (placebo) globules (moistened with either medicine or dispensing alcohol), and they were not allowed to influence the study in any ways. The prescriptions were sent to the pharmacist who was responsible for dispensing as per the random number chart from either of the two sets of vials of identical appearance – one containing genuine homoeopathic preparation prepared in the standard manner, or placebo, indistinguishable from each other, along with a set of vials containing known 'non-medicated' cane sugar globules no. 30 (placebo). Randomisation codes '1' and '2' were labelled on the vials in strict confidentiality. The codes were broken at the end of the trial after the data set was frozen. Blinding was checked for all patients early in the trial by an independent third party, before the treatment was expected to take effect by asking the patients in which group they believed they were in; otherwise, any positive effect would break the code, especially when chances of diffusion of treatment could not be removed.

Statistical methods

All the collected data in the standardised format were subjected to data extraction in a specially designed Microsoft Office Excel® Spreadsheet v. 2007(Redmond, Washington, United States of America) and underwent statistical analysis – both descriptive and inferential. The protocol-compliant sample was analysed in the end. Given the objective of classifying the patients as 'responders' and 'non-responders' in the two groups over 2 weeks and thereby comparing the two proportions, the authors were of the opinion that a 'per-protocol' analysis was permissible, and seemed to be preferable over an 'intention-to-treat' analysis. Descriptive statistics were presented in terms of absolute values, percentages, means and standard deviations, as appropriate. The groups were checked for comparability of sociodemographic characteristics and outcome measures at baseline using independent t-test (for continuous data) or Chi-square test (for categorical data). The number of responders was assessed as per the ARMSC and CTC scoring after 7 and 14 days. Relative risks (RRs) with 95% confidence intervals (CIs) were reported. Chi-square tests were performed to report P values which were set at <0.05 (two tailed) as statistically significant. SPSS ® IBM ® version 20 software was used for the analysis of the data. Graphs were generated in Microsoft Office Word ® v. 2007. Reporting adhered to the CONSORT [26] and ReDHoT guidelines [27] for reporting trials.

Ethical issues

Prior to enrolment, each patient was provided with a patient information sheet in local vernacular Hindi, detailing the study aims and objectives, methods, risks and benefits of participating and confidentiality issues. Subsequent to this, a written informed consent was obtained. Ethical clearance was obtained prior to initiation. Thus, the study conformed to the ethical standards.

 Results



Participant flow

A total of 144 patients with breast cancer suffering from the adverse effects of radiotherapy or chemotherapy were screened preliminarily; 36 were screened out. The rest of the majority of 108 patients fitted the symptoms of the pre-identified medicines, with the reason being that the therapeutic approach of using the pre-identified medicines is 'clinical' (based on 'common' symptoms) instead of 'individualised' (i.e., based on 'uncommon, peculiar, characteristics symptoms'). These 108 patients underwent detailed screening as per the specified eligibility criteria; twenty were excluded for varying reasons. As the considered symptomatology pertained to the common symptoms, none were excluded on the basis of symptom dissimilarity. A total of 88 patients were enrolled in the study and randomised to either verum (UC + Homoeopathy) or control (UC + Pl) in 1:1 ratio. A total of eighty patients completed the follow-up; eight patients dropped out – four in each group. The protocol-compliant sample (n = 80) was analysed in the end [Figure 1].{Figure 1}

Baseline data

The two groups were comparable as per baseline features that is, no statistically significant differences existed between the groups in terms of age (χ2 = 0.732, P = 0.947), residence (χ2 = 0.853, P = 0.356), education (χ2 = 0.524, P = 0.769), employment (χ2 = 0.321, P = 0.852), socioeconomic status (χ2 = 0.970, P = 0.616), duration of illness (χ2 = 0.643, P = 0.996), breast cancer types confirmed through biopsy (χ2 = 0.182, P = 0.999), therapies instituted (χ2 = 0.050, P = 0.823), lymph node involvement status (χ2 = 0.667, P = 0.414), number of chemotherapy cycles instituted (χ2 = 0.193, P = 0.661) and chemotherapy regimens (χ2 = 0.683, P = 0.953) and ARMSC (χ2 = 0.260, P = 0.878) and CTC grades (χ2 = 0.712, P = 0.701). Lymph node involvement was found in six cases only; three in either groups [Table 2].{Table 2}

Numbers analysed

After 14 days, four patients dropped out in each group that is, 80 patients were protocol compliant that entered into the final analysis.

Outcomes and estimation

The numbers of responders versus non-responders as per ARMSC score after 7 days (11/18 vs. 1/19 [61.1% vs. 5.3%], RR = 3.3, 95% CI = 1.7–6.3, χ2 = 10.7, P = 0.001) and 14 days (16/18 vs. 1/19 [88.9% vs. 5.3%], RR = 9.4, 95% CI = 2.5–35.2, χ2 = 22.8, P < 0.001) was statistically significant favouring verum over control. Similar results were obtained also according to CTC scoring after 7 days (15/22 vs. 2/21 [68.2% vs. 9.5%], RR = 3.3, 95% CI = 1.7–6.3, χ2 = 13.1, P < 0.001) and 14 days (21/22 vs. 4/21 [95.5% vs. 19%], RR = 15.1, 95% CI = 2.2–102.4, χ2 = 22.7, P < 0.001) [Figure 2] and [Figure 3].{Figure 2}{Figure 3}

Harms

No harms and adverse or unintended effects were reported from either group during the trial. Temporary worsening of the existing complaints followed by rapid improvement (probably 'homoeopathic aggravation') was observed in 18 out of 40 cases (45%) in the verum arm only.

Medicines used

Patients presenting with ARMSC Grade I (follicular, faint or dull erythema epilation; dry desquamation or decrease in sweating), Grade II (tender, bright erythema; patchy, moist desquamation or moderate oedema) and Grade III (confluent, moist desquamation other than skin folds; pitting oedema) were given Arsenicum album 30C, Belladonna 30C and Radium bromide 30C, respectively. In non-responding cases, after due re-assessment of the cases, Carcinosinum 200C, Apis mellifica 30C and X-ray 30C were prescribed. Patients presenting with CTC Grades I, II and III were prescribed with Ipecacuanha 30C, Arsenicum album 30C and Cadmium sulphuricum 30C, respectively. The non-responders were reassessed and were prescribed Cadmium sulphuricum 30C and Phosphorus 30C. Doses were administered as per individual requirements as decided appropriate to the case and condition. Any reduction in grades was marked as 'responded' [Table 3], [Table 4], [Table 5], [Table 6].{Table 3}{Table 4}{Table 5}{Table 6}

 Discussion



Our study found that UC + Homoeopathy produced significant treatment benefit in comparison to UC + Pl by reducing ARMSC and CTC scores, thus mitigating the dermatological adverse effects of radiotherapy and vomiting of chemotherapy in women suffering from breast carcinoma.

The study design was 'gold standard' (i.e., RCT) to examine the efficacy of any intervention; here UC + Homoeopathy. We used 'double-blind' technique in order to minimise bias to the maximum possible extent. Two pre-validated scoring systems – ARMSC and CTC – were used, thus substantiating the validity of the study findings. Instead of complexes or standardised medicines, we opted for pre-defined, homoeopathic medicines, of which, a few (e.g., Radium bromide, Cadmium sulphuratum, Belladonna and X-ray) were experimented in trials previously,[12],[17] but on individualistic approach only. Frass et al., 2015[7] studied the efficacy of additive individualised Homoeopathy to standard anti-cancer care in an open, pragmatic RCT design on 373 patients, revealing significant improvement in global health status and subjective well-being. We used pre-defined remedies in the place of individualised ones using more robust double-blind, placebo-controlled design, but on a relatively less number of patients. In a single-blind RCT on 254 patients by Pommier et al. in 2004,[10] Calendula ointment was found to be better than trolamine ointment in preventing post-radiation dermatitis. Unlike this study, we did not use external applications in our trial, and ours was a double-blind trial. The RCT by Daub et al., 2000,[13] was placebo controlled, but open labelled and compared two complexes – Vomitusheel S suppository and Gastricumeel tablets – against placebo in 44 patients, but found no difference with placebo. Like ours, Kulkarni et al., 1988,[14] compared two predetermined remedies – Cobaltum and Causticum – with placebo using double-blind design in 82 patients with radiotherapy and found significant symptom relief in the verum group than control group. In another study of similar design with ours, Balzarini et al., 2000,[17] elicited a non-significant trend favouring two predetermined remedies – Belladonna 7 CH and X-ray 15 CH – over placebo. In another double-blind, placebo-controlled trial, Oberbaum et al.,[15] found promising effects of a complex Traumeel S in comparison with placebo in thirty children suffering from radiation-induced stomatitis. Contrarily, in another double-blind, placebo-controlled trial on 190 patients, Sencer et al., 2012, could not find any beneficial effect of Traumeel S against placebo. Thus, overall, RCTs testing complex remedies have remained contradictory in outcomes, whereas the trials with predetermined remedies generated promising results. We planned UC to continue uninterruptedly and mutually in the two study arms because of ethical concerns. The drop out rate was 10% in the study; thus provision should be made for such attrition during sample size calculation in future trials. The study was conducted at a single centre. As Homoeopathy prescriptions largely depend on the skill of the prescribers, the study outcomes may vary in different settings and with different prescribers. Our study was underpowered because we actually ran subgroup analyses on a relatively smaller sample than recruited to account for two different groups of patients receiving either radiotherapy or chemotherapy, hence the efficacy of Homoeopathy cannot be established or claimed. Hence, an adequately powered trial is warranted with patient-rated, validated, quality-of-life outcomes. The basis of treatment was pre-identified homoeopathic medicines, thus presenting a form of contemporary Homoeopathy practice. However, one important limitation was that we restricted our analysis to protocol-compliant sample only. Using an intention-to-treat approach would have been more appropriate than this. Having used only centesimal potencies in this trial for the purpose of convenience in dispensing and intake of dosage, pragmatic trials comparing the effectiveness of centesimal and 50 millesimal potencies or Homoeopathy versus UC might also be promising endeavours. We also restricted the choice of the remedy from a list of pre-defined medicines. If we had not opted for this identified list prior to the identification of the medicines, the option would have been there for a long array of medicines to choose from, and that might have blurred the scenario by introducing further bias in this relatively less explored condition. We also limited our assessment to dermatological adverse effects of radiotherapy and vomiting of chemotherapy, the conditions frequently reported in the author's practice. Treatment effects in other adverse events also need to be explored in future trials by engaging a number of specialists of the concerned fields.

The results of our study warrant cautious interpretation and sincere consideration of Homoeopathy as an adjunctive and complementary aid to standard care in mitigating radiotherapy- or chemotherapy-induced adverse effects, especially dermatological conditions and vomiting. Studies those assessed the efficacy of the same remedy or complex formulations, being prescribed to all the participants in a trial, were inherently contradictory with the principles of Homoeopathy itself. Hence, adherence to the basic doctrines of Homoeopathy is suggested for any future trials aiming to assess the efficacy or effectiveness of Homoeopathy.

 Conclusion



Our study found significant treatment benefit of pre-defined homoeopathic medicines against placebo in reducing ARMSC and CTC scores in the mutual context of UC. Through the integration of Homoeopathy into conventional care, an integrative medicine approach may facilitate mitigating the dermatological adverse effects of radiotherapy and vomiting of chemotherapy in an effective manner. We propose independent replications and further research evaluating both cost and clinical effectiveness in a multicentre approach on a larger sample size.

Acknowledgement

We deeply acknowledge our staff, pharmacist and patients for their sincere participation in the study.

Financial support and sponsorship

Nil.

Conflicts of interest

None declared.

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