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Research Adverse Events

Research Adverse Events

PILLAR #7

To be able to RESEARCH ADVERSE EVENTS, you need to know which adverse events affect the quality of life and treatment (dis-)continuation the most, so you can focus on those first. Ideally, adverse event exploration studies should already be performed during phase I and II research, when the first patients are consuming a drug for the very first time.

Besides providing training about performing adverse event research in all 4 phases of clinical research, we perform our own Research activities.

 

Research activities of CB Boers Org.

Targeted therapies such as epidermal growth factor receptor inhibitors, multi-targeted tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors have, to a greater or lesser extent, mucocutaneous adverse events (mcAEs) in common. Papulopustular rash, hand-foot skin reaction, and stomatitis are the most serious adverse events. At present, evidence of the effectiveness of the management options for mcAEs is lacking, and the effect of the mcAEs on health related quality of life (HRQoL) and adherence remains poorly understood. The aesthetic discomfort, which is frequently associated with itching or painful skin or nails can lead to a decreased HRQoL and to dose reduction or discontinuation of anticancer treatment.

Al projects of CB BOERS ORG. are generated in close collaboration with world-renowned scientific and clinical experts in the therapeutic area of interest. As up till now the number of controlled studies from which evidence based advice for these mcAEs can be formulated, is very limited, we established two clinical studies. Currently the following research projects are ongoing:

BECET TRIAL (NCT01136005)

This clinical trial is a phase III randomized double-blind trial of Bepanthen® cream versus Cetomacrogol cream in the prevention of papulopustular eruption in patients receiving EGFRI (BeCet) in collaboration with the Impaqtt Foundation (Responsible Party), Waterland Hospital, Leiden University Medical Center, and Bayer.

COMTT TRIAL (NCT01265810)

This clinical trial is a phase III randomized double-blind cross-over trial of supersaturated calcium-phosphate rinse (Caphosol®) versus NaCl 0.9% in the relief of oral mucositis in patients receiving targeted therapy (COMTT) in collaboration with the Impaqtt Foundation (Responsible Party), Waterland Hospital, Leiden University Medical Center, and EUSA Pharma.

 

Gain experience with the 1st version of DERETT

Experienced mcAEs can be assessed using the patient completed mcAEs specific symptom experience diary for targeted therapies (DERETT). DERETT has been generated to effectively assess the experienced dermatological adverse events and effectiveness of supportive care interventions like area involved, severity and duration of the symptoms, used products, effectiveness of various (medical) interventions, treatment adherence and distress from the symptoms. Where we started first with skin reactions, the mucosal adverse events are added too. DERETT provides more relevant and precise information on the patients’ experience than would be provided by the CTCAE grading alone. There is a patient reported outcome (DERETT-P) and a healthcare reported outcome (DERETT-H) available.

 

Gain experience with the 1st version of mIAS SCALE

mTOR inhibitor-associated stomatitis (mIAS) is a dose-limiting toxicity of mTOR inhibitors like everolimus and temsirolimus. The mIAS scale has a subjective component measuring pain and an objective component measuring duration of lesions. The subjective grading criteria can be assessed on a 0-3 numerical analogue scale. The objective grading criteria range from 0 for no visible lesion to 3 for lesion(s) persisting for more than 7 days. It is suggested that dose-modification be considered only when both subjective and objective are grades 3, representing persistent lesions with significant pain, despite anti-toxicity interventions. The mIAS scale will be validated within an upcoming clinical trial.

 

Validating the Dutch version of the FACT-EGFRI-18

The impact of EGFRI-associated mcAEs on patients QoL can be evaluated with the Functional Assessment of Cancer Therapy Epidermal Growth Factor Receptor Inhibitor 18 (FACT–EGFRI-18). The FACT-EGFRI-18 is a dermatology-specific patient-reported outcomes questionnaire, consisting of 18 items encompassing well-being in 3 QoL domains: symptoms, functioning, and emotions. The questionnaire is based on items from dermatologic QoL instruments such as the Skindex. The English version has been translated into Dutch and German and is currently under validation in the BeCet trial.

 

Gain experience with the 1st version of the Modified VHNSS2.0

The Vanderbilt Head and Neck Symptom Survey (VHNSS) was designed to screen for tumor-and treatment-specific symptoms in patients with head and neck cancer undergoing concurrent chemoradiation. items are for instance: xerostomia, thick mucous resulting in choking/gagging, difficulty chewing/swallowing, speaking, voice changes with hoarseness and trouble being understood, dental complaints, tooth sensitivity, loose teeth, tooth cracking/chipping, taste changes affecting desire to eat, type and amount of food eaten, mucosal sensitivity, sensitivity to hot, spicy, or acidic foods; sensitivity to dryness, food choices, and tooth brushing. Because the functional implications of targeted therapy associated oral adverse events show almost the same adverse events as measured in this survey, with little changes the survey will be a good instrument to use for this population too.

So, for this population, four questions are removed from the VHNSS2.0. Question 1 (feeding tube), 32 (trouble with hearing), 49 (limitation in jaw movement) and 50 (limitations neck/shoulder movement) are removed because they are related to the tumour field and radiation therapy and not caused by adverse events of targeted therapy. Question 2 (teeth) and 3 (dentures) are moved to the Patient characteristics form because in this population it is worthwhile to know, but makes no sense to assess three times a week. One question about aphthous ulcers is added to the VHNSS2.0. Two questions are added concerning symptoms of HFSR, two about rash changes, two about eyes, and three about diarrhoea. Completion time is less than 10 minutes. To make the VHNSS2.0 suitable for the Dutch population, the questionnaire is translated into Dutch following the steps of the FACIT organisation and is currently under validation in the COMTT trial.

 

Gain experience with the 1st version of the HFS-14

The HFS-14 has been translated into Dutch but is not validated. The HFS-14 is a QoL scale for patients experiencing chemotherapy-associated hand-foot syndrome and targeted therapy-associated hand-foot skin reaction. This instrument measures its severity and its impact on patients. It addresses the body parts affected (hand, foot or both), symptoms, and social impact (poster). The 14 items are organized in 2 modules, differentiated by involvement of the “feet-specific” or the “hand-specific” events. The validation confirmed the internal consistency and very high reproducibility of the questionnaire.

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