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Questions & Answers

QUESTION: Do all targeted agents have similar adverse events?

ANSWER: There are differences between the agents. Some agents are associated with hand-foot skin reaction, while in others aphthous-like ulcerations are seen. When side-effects occur, the appearance is basically the same, but the grade and duration is different across different agents. mTOR inhibitors produce less rash although the clinical findings may be the same as with other agents and treatment.


QUESTION: What is the relationship between the mucosal and dermatological toxicities? What are the mechanisms underlying the adverse events?

ANSWER: Many of these medications have a binding site in the skin and mucosa epithelial cells, and the side-effects develop at both tissue compartments.


QUESTION: Which cream or ointment is optimal for moisturizing the skin?

ANSWER: For skin involvement, generally patients should use a fat cream, balsam, or body butter. A fat cream, balsam or body butter is preferred when the product is provided in a pot. The other products are or too watery or to oily and will not keep the skin sufficiently moisturized.


QUESTION: Should a cream including vitamin K or Bepanthen cream be used prophylactically for papulopustular rash?

ANSWER: An emollient is needed to prevent drying of the skin and reduce papulopustular rash severity and duration. Results of vitamin K1 studies are promising, however, randomized double blind trials are needed. A current study using pro-vitamin B5 (dexpanthenol (Bepanthen®)) cream is currently conducted. At this time we do not know if a cream with a certain substitute is preferable over the vehicle.


QUESTION: In patient information brochures it is indicated not to apply petrolatum to body sites with sebaceous glands, while this information is not traceable to guidelines and especially the face and neck should receive extra protection for the rash. Are you sure that this information is right? And how should one deal in practice with this conflicting information?

ANSWER: The information is not contradictory, but the question shows that the difference between a cream and petrolatum is not known. Targeted agents dry the skin. Use of a fatty cream is recommended. They bring oil and maintain hydration of the skin. However, petrolatum is too fat and can clog the sebaceous glands. A cream consists of the correct ratio water and oil and should be used.

The different topical products for the skin, are dependent on their composition, divided into petrolatum, ointment, body butter, balm, cream, lotion, and gel:

Petrolatum (Vaseline) is the most oily and gel the most watery product. In general, the more watery a product is, the easier it is to spread and the better it can penetrate into the skin. Petrolatum should be applied only to areas with few sebaceous glands, such as fissures on the hands/fingers and feet/heels.


QUESTION: I prescribe doxycycline 100 mg once a day. Is this appropriate for management of the skin rash?

ANSWER: The literature suggests 100 mg once or twice a day given prophylactically. When managing mucocutaneous adverse events the dose recommended is 200 mg/day. If there is no response after 14 days, specimen are required for cultures in order to identify the pathogen and to identify any antibiotic resistance and prescribe antibiotics based on culture results.


QUESTION: Is it allowed to be exposed to sun when a skin reaction is present?

ANSWER: Sunlight in general exacerbates skin reactions. So it is not forbidden, but one should know that the severity will increase with sun exposure, even when sun protection is used.


QUESTION: Is there an adverse event tool to use in clinic for patients on targeted therapy? Is there one single, short questionnaire?

ANSWER: There is not one single questionnaire available which captures all side effects. There are however, a couple of questionnaires available, as outlined in chapter 5, that address adverse events in general and quality of life.


QUESTION: Do you use the FACT–EGFRI-18 questionnaire in daily practice in your clinics?

ANSWER: Yes. This can be useful in clinical practice. Within clinical trials the questionnaire is completed at initiation of therapy for pretreatment (“baseline” data) in order to be able to identify adverse event and assess severity and patient impact of the adverse events.


QUESTION: There are already so many trials performed wherein the side effects are captured as a part of the evaluation. Why is research primarily focusing on adverse events needed?

ANSWER: In clinical trials, where the effectivity of a product is the primary endpoint, no detailed adverse event data is captured. Generally, no physical examination is performed addressing for instance mucocutaneous adverse events. In addition, no adverse event questionnaires are completed. As a result we are missing essential information about the appearance, duration, severity, symptom burden, effect on quality of life of the adverse event(s) and the effectiveness of interventions.


QUESTION: When my patients develop painful stomatitis, I tell them to stop with the saline containing mouth rinses. Is there something else I can advise?

ANSWER: When patients have mouth sores, they should increase not decrease the mouth rinses. The most important measure is that they rinse, preferably with a saline and/or a bicarbonate containing product. But when that is too painful, plain water may be trialed. When pain is present this should be managed with topical applications and/or systemic analgesics.


QUESTION: Is it allowed to drink alcohol while oral ulcerations are present?

ANSWER: Alcoholic drinks and alcohol containing mouthwashes are potential dehydrating and irritating to the mucous membranes of the mouth and therefore should be avoided or their use at least decreased.


QUESTION: In case of diarrhea, in my opinion it doesn’t matter which definition I use. It still is diarrhea and it should be treated with loperamide, right?

ANSWER: That’s partly right. The recommended initial treatment of choice is loperamide, but high dose loperamide should be used in patients with entire watery stool. With loose stool, a less watery variant of stool, low dose loperamide should be prescribed. Within the CTC score only entirely watery stool is defined as diarrhea, while within the WHO definition the stool is allowed to be loose. So it definitely matters which definition is used, because the treatment depends on this definition.


QUESTION: Is it safe to treat elderly adults with targeted agents?

ANSWER: We have learned that the patient’s age should not be leading factor in treatment decisions. The most important variable is the condition of the patient or biologic age. As per NCCN guidelines, every 70+ patient should receive a brief screening assessment like measure of function, gait speed, or grip strength before treatment. Only those patients identified as high risk patients during screening, are recommended for a comprehensive geriatric assessment before treatment. Geriatric assessment can allow the classification of patients into fit, compromised and frail groups. Fit patients mostly can be treated comparably to younger patients, but compromised and frail patients need special attention. A focused geriatric assessment may facilitate best practices and enhance overall patient care. Age alone is not a barrier in the administration of targeted agents.


QUESTION: Is it safe for elderly patients who have a couple of comorbidities to receive targeted therapy?

ANSWER: There are many trials performed in elderly patients. Very heterogeneous results are seen in these trials. Some conclude that elderly experience greater toxicity than younger patients and that unexpected toxicity may be observed in the elderly population. However, this is not seen in all trials. Currently, the consensus of opinion is that elderly do not experience greater toxicity and that targeted therapy is effective and safe also in unselected elderly subjects.


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