SAMITAL® improves chemo/radiotherapy-induced oral mucositis in patients with head and neck cancer: results of a randomized, placebo-controlled, single-blind Phase II study

Support Care Cancer (2013) 21:827-834. DOI 10.1007/s00520-012-1586-5

Authors: D. Pawar1, R.S. Neve2, S. Kalgane2, A. Riva3, E. Bombardelli3, M. Ronchi3, G. Petrangolini3, P. Morazzoni3

 

Affiliations:

1Drug Research Laboratory, Mumbai, India

2Gokhale Hospital and Ruby Hall Clinic, 40, Sassoon Road, Pune-4110011, India

3Scientific Department, Indena S.p.A., Viale Ortles 12, 20139 Milan, Italy

Study Centre:

Gokhale Hospital, Ghole Road, Near Tukaram Paduke Chowk, Shivajinagar, Pune-5, India.

 

Corresponding Author:

Giovanna Petrangolini, Scientific Department, Indena S.p.A., Viale Ortles 12, 20139 Milan, Italy.

Phone:                         +39-02-57496493

Fax:                 +39-02-57496290

E-mail:             giovanna.petrangolini@indena.com

 

Abstract

This randomised, placebo-controlled single-blind trial investigated the safety and efficacy of SAMITAL®, a formulation of highly standardised botanical extracts, in the treatment of chemo/radiotherapy-induced oral mucositis (OM) in patients with head and neck cancer.

Patients received SAMITAL® or placebo four times daily for up to 50 days during scheduled chemo/radiotherapy. Severity of OM was monitored according to a modified WHO severity scale and pain and quality-of-life assessments were based on the effect of symptoms of OM on relevant daily activities, according to a visual analogue scale.

Mean scores for the severity of OM were significantly (p<0.05 vs baseline) reduced from day 31 until the end of treatment in patients treated with SAMITAL® (n=20). No significant improvement was observed in the placebo group (n=10). Pain reduction was significant from day 4 till end of treatment with SAMITAL® and from day 7 to 21 in placebo patients. SAMITAL® also significantly improved quality of life, as shown by improvements in scores for relevant daily activities including eating, drinking and sleeping. All SAMITAL® patients completed the treatment period but no placebo recipients completed treatment. No severe adverse events were observed with SAMITAL® and systemic absorption of relevant active ingredients was undetectable.

SAMITAL® significantly decreased the severity of chemo/radiotherapy-induced OM in patients with head and neck cancer, with no treatment-related adverse events. Pain relief lasted through the treatment period, and improvements in quality of life were reflected by the significant benefits of SAMITAL® on activities like drinking, eating and speaking.

PMID: 22945882

 

Supplement

Almost all patients with head and neck cancer receiving chemo/radiotherapy treatment develop oral mucositis (OM) and OM is one of the most common dose-limiting toxic effects of chemo/radiotherapy in these patients. The severity of OM varies from patient to patient, and also depends on treatment type, duration and intensity. Characterised by inflammatory lesions and ulcers of the mucosa, OM is associated with considerable pain, dysphagia, parenteral nutrition supplementation, and an increased susceptibility to infections, particularly bacterial and fungal infections. However, despite the predictability of mucositis, its frequency, debilitating symptoms, and negative impact on the treatment programme and health economic costs of patients with head and neck cancer, an effective therapy for OM has long remained elusive.

SAMITAL® was developed with the aim of addressing the challenges of treating OM. It is a combination of three highly standardised botanical drug extracts. These extracts from Vaccinium myrtillus (bilberry), Macleaya cordata fruits and Echinacea angustifolia roots, contribute to improving key stages of OM. SAMITAL® was produced to allow the formation of a gel-like suspension and subsequently prolonged exposure of the oral mucosa to the active ingredients. It is noteworthy that SAMITAL® composition is standardised and reproducible. A clinical study conducted in Chile using SAMITAL® showed the formulation to be active in the treatment of gastrointestinal mucositis of varying aetiologies, prompting the development of SAMITAL® as a pharmaceutical product under the USA FDA’s Guidance for Industry: Botanical Drug Products released by the Center for Drug Evaluation and Research (June 2004).

The aim of this Phase II single-blind study was to investigate the activity of SAMITAL® compared with placebo in patients with head and neck cancer with chemo/radiotherapy-induced OM. The safety profile of SAMITAL® and systemic exposure to the most relevant active ingredients were also investigated. Results indicate that SAMITAL® provides well tolerated and effective relief in patients with OM induced by chemo/radiotherapy in patients with head and neck tumours. This was a preliminary study and the results of which are encouraging and provide evidence that SAMITAL® can play an important role in the management of chemotherapy/radiation-induced OM. These outcomes have supported the approval by the Ethical Committee of the Istituto Oncologico Veneto in Padua of one prophylactic double-blind, randomized, placebo-controlled clinical trial in patients with head & neck cancer ongoing in Italy (EUDRACT No 2012-002046-20). Furthermore, in the USA a therapeutic multicenter clinical trial in head and neck cancer patients (IND 104,011) has been approved by FDA.

New results have also been established for the relief of mucositis induced by chemotherapy. A case series in paediatrics reported the treatment of 20 patients undergoing chemotherapy for a range of oncological conditions (Bertoglio et al., 2012). Patients received oral SAMITAL® initially to treat gastrointestinal mucositis and were then given SAMITAL® prophylactically to prevent recurrences with successive cycles of chemotherapy. Moreover, the efficacy and safety of SAMITAL® in reducing mucositis in patients undergoing treatment for haematological malignancies were investigated (Bertoglio et al., in publication). In both studies, patients showed clinically-relevant reductions in WHO mucositis grade together with a reduction in pain, mucosal erosions, bleeding, dysphagia/feeding impairment and improvements in quality of life. SAMITAL® was well tolerated and no local or systemic pharmacological, allergic, toxic, synergistic-antagonistic side effects were reported. Of note, SAMITAL® also showed efficacy when administered prophylactically.  These results add weight to previous experiences with SAMITAL®. New controlled trials to confirm SAMITAL® benefits for the relief of mucositis in different oncological pathologies are under planning.

 

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