Management of patients on targeted therapies

Management of patients on targeted therapies

Introduction

Targeted therapies have profoundly changed the management of certain pathologies in recent years.

These are treatments using biological products, which contrasts them with synthetic chemotherapy molecules.

Indeed, these therapies are not without side effects and the dentist must therefore be aware of their potential oral and dental repercussions.

Definition

– “Targeted therapies” are treatments directed against molecular targets (receptors, genes or proteins).

-They have the advantage of being less toxic by sparing healthy cells and allow treatment to be individualized according to the pathology and molecular biology of the patient.

-Targeted therapies can act at different levels of the cell:

on growth factors (which are messengers triggering the transmission of information within a cell),

on their receptors (which allow the transfer of information inside the cell)
on elements inside cells.

Management of patients on targeted therapies

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Depending on the nature of the molecule used, we distinguish:

– monoclonal antibodies that interact with membrane receptor ligands or with the extracellular part of the receptor, preventing the molecule from binding. They have the suffix “mab.” They are administered intravenously.

– tyrosine kinase inhibitors (TKIs) , which are small molecules that penetrate the cell where they inhibit signaling pathways by acting on the intracellular portion of the receptors. They have the suffix “nib” and are administered orally.

Targeted therapy molecules can also be classified according to their mode of action. We therefore distinguish:

anti-angiogenics

– HER inhibitors (Herceptin)

– inhibitors of KIT, a membrane receptor

mTOR (mechanistic target of rapamycin) inhibitors
cytokine
3. Therapeutic indications

Use in rheumatology

Therapeutic class	Generic Name	Trade name	Mode and frequency of use	Indication
AntiTNF	Infliximab	Remicade	3 mg/kg to 10 mg/kg IV every 6 to 8 weeks	Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease, psoriasis
AntiTNF	Etanercept	Enbrel	50 mg subcutaneously every week	Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis, psoriasis
AntiCD20	Rituximab	Rituxan	1 g intravenously 2 doses and as needed thereafter	Rheumatoid arthritis, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, Wegener’s granulomatosis, microscopic polyangiitis

Indication in internal medicine

Systemic lupus erythematosus
Sarcoidosis: efficacy of anti-TNF in refractory and severe forms
Primary or secondary necrotizing vasculitis
Behçet’s disease as a first-line treatment, especially in cases of ocular, neurological or digestive involvement

Indication in neurology: The use of Natalizumab, interferon-b 1a and 1b in multiple sclerosis

4-Oral manifestations of targeted therapies

Mucositis/Aphthoid Ulcers: A number of targeted therapies can induce inflammation of the oral mucosa. However, the lesions observed differ markedly from chemotherapy-induced mucositis; they appear much smaller in size and often take on an aphthous ulcerated appearance.

However, the functional impact can sometimes be significant and also require a concession or even a temporary cessation of anticancer treatment.

The management of these lesions is based on symptomatic measures, which are not yet strictly codified. This must include at least pre-therapeutic oral rehabilitation, strict education in oral hygiene and the use of mild mouthwashes several times a day (sodium bicarbonate).
Lichenoid reactions:

They are mainly associated with imatinib, BCR-ABL (Philadelphia gene or Ph1 chromosome) and c-Kit.

Clinically, these lichenoid reactions do not differ from those observed in lichen planus, with an association of reticulated lesions, atrophy and inflammatory ulcerations.

The cheek mucosa and tongue are mainly affected.

Therapeutic management is based on local corticosteroid therapy and targeted treatment can be maintained.

Secondary hyperkeratoses:

The progressive development of hyperkeratotic intraoral lesions only concerns serine threonine kinase inhibitors targeting BRAF (B-raf proto-oncogene).

These lesions result in a homogeneous hyperkeratosis which predominates on the linea alba, the lateral edges of the tongue, the hard palate and the marginal gingiva.

Geographic languages

Molecules with antiangiogenic activity, i.e. targeting VEGF (Vascular Endothelial Growth Factor) or its receptors, can promote the development of benign migratory glossitis or geographic tongue.

The clinical presentation is quite comparable to that of idiopathic geographic tongue, that is to say with areas of depapillation surrounded by a raised serpiginous border.

Management is simply based on reassuring the patient that these lesions are strictly benign. Cancer treatment can be continued.

Dysgeusia:

Altered taste may also be associated with the use of several targeted therapies.

It appears particularly frequent with sunitinib but also reported with anti-EGFR (Epidermal Growth Factor).

Osteochemonecrosis:

Targeted anti-angiogenic and anti-responsive therapies can induce osteonecrosis of the jaws.

Support

A) Prevention before the introduction of therapies :

A rigorous clinical examination supplemented by a dental panoramic scan constitutes the minimum initial examination.
Removal of active or potential infectious foci by extracting teeth with periodontal or endodontic lesions or deep caries.

If invasive dental treatment, such as extractions, is performed beforehand, a healing period of at least 15 days must be observed before implementing targeted therapy treatment.
If the patient is to receive anti-angiogenic treatment with Bevacizumab or Sunitinib, he/she should be informed of the possible risk of developing osteochemonecrosis of the jaws.

Treatment of periodontal pathologies
Sealing existing dental care
Resumption of care with sharp or cutting edges that could irritate the mucous membranes
Motivation for oral hygiene by emphasizing brushing methods
Healthy lifestyle and dietary advice by stopping smoking, and avoiding spicy foods that are too hot or too cold.

B) Support during treatment with targeted therapy:
Precautions during non-surgical care

For this type of care, there are no contraindications and it is not necessary to modulate the treatment with targeted therapy.

According to AFSSAPS, antibiotic prophylaxis is recommended during invasive procedures.

Precautions during surgical care
If surgical care is considered in patients receiving targeted therapy, special attention should be paid to the potential occurrence of postoperative bleeding and infections, particularly OCN in patients receiving anti-angiogenic agents such as Bevacizumab (Avastin) or Sunitinib (Sutent).
It is therefore necessary to inform the patient and be vigilant in the conduct to be adopted.
Discontinuation of targeted therapy is recommended before undertaking any surgical procedure.
The methods for suspending treatment vary depending on the molecule:

monoclonal antibodies: stop 2 to 3 weeks before the procedure
ITK: stop 5 to 7 days before the procedure.

Treatment resumes once mucosal healing has been achieved and with the agreement of the oncologist.

Operating protocol

– under antibiotic cover: they are started 48 hours before the operation and continued until healing (approximately 15 days);

– careful disinfection of the operating field, irrigation with Chlorhexidine

– local or loco-regional anesthesia: avoid intra-ligamentous anesthesia

– atraumatic surgery

– regularization of alveolar processes

– local hemostatic means (intra-alveolar resorbable material)

– waterproof sutures

– possible use of a biological glue

– post-operative advice

– healing control.

Special case

anti-TNF

In practice, for patients on anti-TNF, considered immunocompromised, we will propose:

• For the performance of non-invasive procedures (e.g.: non-bloody preventive procedures, conservative care, non-bloody prosthetic care, post-operative removal of sutures, fitting of removable prostheses, fitting or adjustment of orthodontic appliances, dental X-rays, etc.), prophylactic antibiotic therapy is not indicated and stopping anti-TNF is not justified.

• For the performance of invasive procedures (likely to induce a local, distant or general infection), prophylactic antibiotic therapy is usually recommended.

Discontinuation of anti-TNF should be performed under the same conditions as those recommended in low-risk infectious surgery.

• For scaling, we offer prophylactic antibiotic therapy without stopping the anti-TNF.

Duration of discontinuation of anti-TNF alpha before surgery:

Etanercept: at least 2 weeks
Infliximab: at least 4 weeks
Adalimumab: at least 4 weeks

Rituximab

Regular oral hygiene and care are recommended . In case of poor oral health, appropriate care should be provided before starting treatment with rituximab.

▷ Routine care (cavities, scaling): Antibiotic prophylaxis can be offered.

▷ Care with infectious risk (extraction, apical granuloma, abscess, etc.): Do not perform the 2nd rituximab infusion if the treatment must take place between 2 infusions.

But most often, the medication cannot be stopped because the cycle of two infusions will have been carried out with consequences on immunity for at least 6 months. It is then recommended to offer antibiotic prophylaxis.

▷ Implants: There are no special precautions to take while remaining vigilant about the potential occurrence of infections.

Conclusion

The dentist therefore has a key role in the prevention and/or treatment of oral and dental after-effects secondary to targeted therapies, hence the importance of patient care by their dentist before, during and after their cancer treatment.
The main objective is to avoid the appearance of complications linked to these treatments and thus improve the quality of life of patients.

Bibliographic references

Vincent Sibaud, Emmanuelle Vigarios. Oral toxicities of targeted anticancer therapies. Med Buccale Chir Buccale 2015;21:149-155.
French Agency for the Safety of Health Products (AFSSAPS). Prescription of antibiotics in oral and dental practice. July 2011.
Recommendations of the French Society of Oral Surgery (SFCO). Management of oral and dental infectious foci. 2012
Pauline Tamburini. Prescriptions and precautions in dentistry for patients undergoing anti-cancer treatment. Thesis: Chir-Dent: Nancy: 2015.
Petit Emilie. Targeted therapies in the treatment of cancers: oral and dental adverse effects and management in dentistry. Thesis: 3rd ^cycle sci.odontol.: Strasbourg: 2016; No. 48.
Cynthia Pierre. Rules for prescribing antibiotics in oral surgery. Th.: Chir.-Dent.: Nancy 2018.
Rheumatism and Inflammation Club. Fact sheets. http://www.cri-net.com (accessed 04/02/2023).