Comparative evaluation between Quality of life (Qol), Adverse events

and Survival analysis of Mistletoe for the treatment of solid tumors

Contents1. Introduction

2. Objective

3. Methods

4. Results

5. Discussion

6. Conclusion

7. References

Contents1. Introduction

2. Objective

3. Methods

4. Results

5. Discussion

6. Conclusion

7. References

Introduction

• Mistletoe is a total extract of European mistletoe (Viscum album) used as a complementary or alternative therapy.

• Mistletoe is mainly used in breast, uterine, gastric, head and neck ,cervical cancer etc.

• As it possess immunomodulatory actions, indicated in the therapy of oncology.

Objectives

• In the present investigation, various outcomes of Mistletoe therapy such as

– Quality of Life

– Adverse events

– Survival analysis were comparatively appraised.

Methods

• Inclusion criteria:

– Mistletoe was used for solid tumors

– In which randomization done

– Published after 2001

• Exclusion criteria:

– In which Mistletoe was not used

– Where non-randomization used

– Studies published other than English language

– Animal and in vitro studies

Methods

• Search strategy

MeSH terms:

“Randomized controlled trial”, “Mistletoe”, “Cancer”, “Mistletoe preparation”, “Viscum album”

• Data bases• Pubmed and Google

• Period covered:

2001 – April 2013

Results

Proportion of Cancers

Characteristics of Studies:S. No Author name Type of cancer

1. Semiglazov et al., 2006 Breast cancer

2. Piao et al., 2004 Breast, ovarian and Non-small lung cancer

3. Kim et al., 2012 Gastric carcinoma

4. Semiglazov et al., 2004 Breast cancer

5. Steuer-Vogt et al., 2001 Head and neck squamous cell carcinoma.

6. Grossarth-maticek and ziegler, 2008 Corpus uteri cancer

7. Grossarth-maticek and ziegler, 2007 Ovarian cancer

8. Grossarth-maticek and ziegler, 2006 Breast cancer

9. Kleeberg et al., 2003 Melanoma

S. No Author name Type of cancer Study design Qol

1 SEMIGLAZOV et al., 2006

Breast cancer Randomized, double blind

FACT-G scale; Global Quality of Life Scale) andSpitzer's uniscale

2. Piao et al., 2004 Breast cancer Randomized clinical trial

Measured by FLIC, TCMI and KPI

3. Kim et al., 2012 Gastric carcinoma Randomized, controlled

EORTC QLQ-C30 and -STO22

4. SEMIGLAZOV et al., 2004

Breast cancer Randomised, placebo-controlled

GLQ-8and Spitzer’s uniscale.

5. Steuer-Vogt et al., 2001

Head and neck squamous cell carcinoma.

Randomised controlled clinical trial

(EORTC) Quality of Life-score 30 (QLQ-C30)

Quality of Life

S. No Author name Medication

ADR related to Mistletoe

1. SEMIGLAZOV et al., 2006

PS76A2, an aqueous mistletoe extract standardised to mistletoe lectins

Reddening of skin,and allergic skin reaction, in one patient acute otitis

2. Piao et al., 2004 HELIXOR – standardized mistletoe extract

Fever, pruritus and inflammatory changes at the injection site.

3. Kim et al., 2012 AbnobaVISCUMW Q 20 mg post-operative bleeding, injectionsite like local pain, itching, rash or urticarial, chest pain,

4. SEMIGLAZOV et al., 2004

Lektinol (aqueous mistletoe extract) subcutaneously

local reaction at the injection site, headache, whitecell and reticulo-endothelial system disorders, gastro-intestinal system disorders, resistance mechanism disorders, red bloodcell disorders

5. Steuer-Vogt et al., 2001

Subcutaneous (s.c.) injections of a mistletoe extract(Eurixor1, biosyn)

Rubor andprurigo, induration, Vesiculation,

Adverse events

S. No Author name Study design No of patients

Survival analysis done by

Hazard ratio

1. Grossarth-maticek and ziegler, 2008

Randomized and non-randomized

prospective controlled

254 pairs Wilcoxon paired sample test and cox proportion hazard

model

0.36 (0.16,0.82)

2. Grossarth-maticek and ziegler, 2007

Randomized and non-randomized

prospective controlled

178 pairs Wilcoxon paired sample test and cox proportion hazard

model

0.40 (0.15, 1.03)

3. Grossarth-maticek and ziegler, 2008

Randomized and non-randomized

prospective controlled

197 pairs Cox proportional hazard regression

model

0.52 (0.23, 1.17)

4. Kleeberg et al., 2003

Prospective, randomised phase III

adjuvant trial

830 patients

Cox proportional hazard regression

model

1.32 (0.93, 1.87)

Survival analysis

Discussion

• QoL was significantly improved in Mistletoe treated arm.

• Mistletoe also ameliorates the symptomatology of the cancer patients.

• Mistletoe contributes to the clinical efficacy and tolerability of conventional treatment

• Various adverse events have been recorded by investigators which encompass a number of organ/ systems.

• Allergic skin reaction, pain at injection site and reticulo-endothelial system disorders, gastro-intestinal system disorders, resistance mechanism disorders, red blood cell disorders.

• Survival analysis done by using Wilcoxon paired sample test and cox proportion hazard model and hazard ratio was reported to 0.36 to 1.32.

• In melanoma patients, Mistletoe doesn’t shown any significant clinical benefit.

Conclusion

• Adjuvant treatment of cancer patients with Mistletoe provides a better chance of survival to patients.

• Transparent design and clear endpoints will be needed in the forthcoming trials to enable us to unravel hidden properties

References• Grossarth-Maticek R, Ziegler R. Randomised and non-randomised

prospective controlled cohort studies in matched-pair design for the long-term therapy of breast cancer patients with a mistletoe preparation (Mistletoe): a re-analysis. Eur J Med Res. 2006 Nov 30;11(11):485-95.

• Grossarth-Maticek R, Ziegler R. Prospective controlled cohort studies on long-term therapy of ovairian cancer patients with mistletoe (Viscum album L.) extracts Mistletoe. Arzneimittelforschung. 2007;57(10):665-78.

• Grossarth-Maticek R, Ziegler R. Randomized and non-randomized prospective controlled cohort studies in matched pair design for the long-term therapy of corpus uteri cancer patients with a mistletoe preparation (Mistletoe). Eur J Med Res. 2008 Mar 31;13(3):107-20.

• Kim KC, Yook JH, Eisenbraun J, Kim BS, Huber R. Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma - a randomized, controlled pilot study. BMC Complement Altern Med. 2012 Oct 3;12:172. doi: 10.1186/1472-6882-12-172.

• Kleeberg UR, Suciu S, Bröcker EB, Ruiter DJ, Chartier C, Liénard D, Marsden J, Schadendorf D, Eggermont AM; EORTC Melanoma Group in cooperation with the German Cancer Society (DKG). Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus Mistletoe M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis. Eur J Cancer. 2004 Feb;40(3):390-402.

• Piao BK, Wang YX, Xie GR, Mansmann U, Matthes H, Beuth J, Lin HS. Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial. Anticancer Res. 2004 Jan-Feb;24(1):303-9.

• Semiglasov VF, Stepula VV, Dudov A, Lehmacher W, Mengs U. The standardised mistletoe extract PS76A2 improves QoL in patients with breast cancer receiving adjuvant CMF chemotherapy: a randomised, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res. 2004 Mar-Apr;24(2C):1293-302.

• Semiglazov VF, Stepula VV, Dudov A, Schnitker J, Mengs U. Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res. 2006 Mar-Apr;26(2B):1519-29.

• Steuer-Vogt MK, Bonkowsky V, Ambrosch P, Scholz M, Neiss A, Strutz J, Hennig M, Lenarz T, Arnold W. The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial. Eur J Cancer. 2001 Jan;37(1):23-31.