Antineoplastic Agents (Chemotherapy)

Antineoplastic Agents (Chemotherapy)

Section I: Clinical Scenario and Dental Considerations

Clinical Scenario

A 50‐year‐old woman is referred by her haematologist for an urgent dental assessment. The patient reports that the lower left first molar has been acutely painful on 2 occasions, 3 months and 1 month ago. These episodes coincided with intensive chemotherapy, which had to be discontinued.

Intravenous antibiotics were given at the time and the tooth is currently asymptomatic. The haematology team are keen to avoid further interruption of chemotherapy.

The dental appointment has been postponed twice due to febrile neutropenia complicating the patient’s chemotherapy.

Medical History

  • B‐cell acute lymphoblastic leukaemia diagnosed 5 months ago
  • Steroid‐induced type 2 diabetes mellitus
  • Gastro‐oesophageal reflux disease
  • Heart murmur
  • Vitamin D deficiency


  • Currently undergoing alternating cycles of chemotherapy (methotrexate, cytarabine, methylprednisolone) and immunotherapy (blinatumomab)
    • Commenced 4 months ago, with 4 months planned
    • Peripherally inserted central catheter line in situ
  • Platelet transfusions weekly
  • Intravenous immunoglobulin replacement every 3–4 weeks
  • Trimethoprim/sulfamethoxazole
  • Posaconazole
  • Famciclovir
  • Pantoprazole
  • Ranitidine
  • Metoclopramide
  • Ondansetron
  • Metformin
  • Amlodipine
  • Cholecalciferol
  • Potassium chloride

Dental History

  • Regular dental attender: attends every 6 months; has had same general dentist for decades
  • Brushes teeth twice daily using sensitive toothpaste and soft manual toothbrush
  • Previously flossed daily and used electric toothbrush until she was instructed to stop upon commencing chemotherapy
  • Diet: low sugar contact, predominantly drinks water

Social History

  • Occupation: teacher (currently on extended sick leave)
  • Lives alone, has support of friends
  • Alcohol: 1 glass of wine per week prior to chemotherapy; nil now
  • Tobacco consumption: nil

Oral Examination

  • Wearing a headscarf due to complete hair loss
  • Facial and oral tissues appear pale
  • Oral ulceration predominantly affecting the lower labial mucosa
  • Lower left first molar (#36): large disto‐occlusal composite restoration in situ, negative to cold sensibility testing, mild tenderness to percussion, buccal tenderness on palpation
  • Good oral hygiene and gingival health on visual inspection
  • No caries detected
Photo depicts long cone periapical radiograph number 36 demonstrating associated periapical radiolucencies (S).

Figure 12.2.1 Long cone periapical radiograph #36 demonstrating associated periapical radiolucencies.

Radiological Examination

  • Long cone periapical radiograph #36 (Figure 12.2.1) and orthopantomogram undertaken
  • #36: mesial and distal periapical radiolucencies present; small distal deficiency present under the restoration; large restoration with close proximity to the pulpal chamber

Structured Learning

  1. What further information would you require from the oncology team?
    • Timings of each alternate chemotherapy and immunotherapy cycle, and length of breaks between each cycle
    • Most recent full blood count and profile
    • Frequency of platelet transfusions and immunoglobulin replacement
    • Platelet count levels normally achieved post transfusion, and the possibility of achieving higher platelet counts post transfusion (>50 × 109/L)
    • Dose of corticosteroid administered with chemotherapy, and risk of adrenal suppression
    • Need for antibiotic prophylaxis with invasive dental procedures
    • Likelihood of requiring haematopoietic stem cell transplant
    • Overall long‐term prognosis
  2. What are the treatment options for managing the lower left first molar (#36)?
    • Continued pain and infection control with antibiotics if the tooth becomes symptomatic again
      • Advantages: obviates the need for a chemotherapy break; may be preferred if there is a narrow window of time to maximise the therapeutic effects of chemotherapy; avoids potentially invasive dental procedures in a patient with persistently low blood counts; avoids loss of the tooth, allowing definitive treatment (e.g. endodontics) to be provided after the course of chemotherapy is completed
      • Disadvantages: the tooth may pose an infection risk with the risk of repeated infection, local spread and bacteraemia, leading to further cessation in chemotherapy
    • Elective dental extraction
      • Advantages: removes the risk of repeated dental infection and related cessation of chemotherapy; of particular benefit if stem cell transplant is planned
      • Disadvantages: dental treatment will require a chemotherapy break; additional haematological support (platelets ± intravenous immunoglobulin) will need to be discussed and implemented; healing may be delayed; prophylactic antibiotics often indicated; permanent loss of tooth
    • Root canal treatment
      • Advantages: reduces (but does not eliminate) the risk of repeated dental infection; allows the patient to keep the tooth
      • Disadvantages: risk of suboptimal outcomes (patient fatigue and hence ability to tolerate longer treatment appointments, low blood counts may affect the success rate); stem cell transplants, particularly allogeneic, require a more critical approach (i.e. dental extraction preferred)
  3. What factors are considered important in assessing the risk of managing this patient?
    • Social
      • Escort advisable due to likely fatigue
      • Need to be empathetic to the psychosocial impact of cancer (e.g. depression)
    • Medical
      • Increased risk of infection due to leukaemia and chemotherapy
      • Hypoglycaemia risk related to type 2 diabetes mellitus (see Chapter 5.1)
      • Cause of heart murmur (if significant, may impact on dental management/the need for antibiotic prophylaxis)
      • Vitamin D deficiency increases the risk of osteopenia
      • Risk of an adrenal crisis due to corticosteroid medication
      • Drug adverse effects and interactions
    • Dental
      • Dental erosion risk due to gastro‐oesophageal reflux disease
      • Discomfort/secondary infection risk related to the oral ulceration – likely to be related to chemotherapy
      • Pale mucosa likely to be related to underlying anaemia – may be associated with burning mouth/discomfort

  4. The patient wishes to have the #36 extracted as she does not want to risk further infection. The haematologist is in agreement and withholds chemotherapy to allow you to proceed. Blood test results on the day of planned dental extraction are as follows: haemoglobin 98g/L, platelets 19 × 109/L, neutrophils 1.05 × 109/L, lymphocytes 0.79 × 109/L.

    What are the risks?

    • Anaemia
      • Hypoxia can cause fatigue and lethargy; patient may appear poorly motivated; dental care should be adapted according to her tolerance of the planned procedure on the day of treatment
      • Additional increased risk of angular cheilitis, oral ulceration, altered taste, glossitis
    • Thrombocytopenia
      • Bleeding risk
    • Neutropenia and lymphocytopenia
      • Infection risk
  5. What are the minimum blood counts (FBC) to allow you to proceed with extraction of #36?
    • Anaemia
      • There is no universal threshold of haemoglobin concentration at which transfusion of red blood cells is appropriate for all patients
      • However, the general consensus is that red blood cell transfusion is not indicated when haemoglobin concentrations are >100g/L
      • Transfusion of red blood cells is indicated at a haemoglobin concentration of < 70g/L
      • The correct strategy for transfusion of patients with haemoglobin concentrations between 70–100g/L is less clear; clinical judgement plays a vital role in the decision to transfuse red cells or not
      • Perioperative nasal oxygen should be considered
    • Thrombocytopenia
      • There is variation in literature regarding the recommended minimum platelet counts to allow for invasive dental procedures (Table 12.2.1)
      • In general, platelet counts >50 × 109/L (>50 000 cells/mm3) are considered acceptable, although this depends on the complexity and site of surgery
      • Where treatment is urgent, platelet transfusions can be given on the same day as treatment
    • Neutropenia
      • Similarly, there is variation in the recommended minimum neutrophil counts to allow for invasive dental procedures (Table 12.2.1)
      • In general, neutrophil counts >1.0 × 109/L (1000 cells/mm3) are considered acceptable, although this is again affected by the complexity and site of surgery
      • Recombinant human granulocyte‐colony stimulating factor (G‐CSF; filgrastim and pegylated filgrastim) and granulocyte‐macrophage colony stimulating factor (GM‐CSF; sargramostim) may be used to reduce the duration and degree of neutropenia but require ~5 days of treatment to raise the counts
      • The haematologist will advise on the appropriate regime and whether it is suitable (in a small subset of patients G‐CSF may act as a driver for leukaemic cell production)
      • Postoperative antibiotics should be considered
  6. Ideally, when should you have been involved in the pathway of care for this patient?
    • The dental team should have been involved in the patient’s care pathway prior to commencement of cancer therapy so that issues such as the periapically involved #36 could have been identified and this tooth removed (Table 12.2.2)

General Dental Considerations

Oral Findings

  • The mucosa that covers the oral cavity and the entire gastrointestinal tract is especially susceptible to the toxic effects of chemotherapy due to its high rate of cell renewal
  • Oral complications of chemotherapy are common and should be considered before, during and after treatment
  • They are commonly described as acute and chronic changes and can significantly impact on the quality of life for these patients (Tables 12.2.3 and 12.2.4)
  • One of the most significant side‐effects is mucositis, as this can be so debilitating as to result in cessation of chemotherapy; in view of this, grading systems have been developed to monitor its severity (Figure 12.2.2; Table 12.2.5)

    Table 12.2.1 Guidelines for minimal haematological values for performance of invasive dental procedures.

    Guideline, date Platelet count Neutrophil count
    American Academy of Pediatric Dentistry, 2018
    • >75 000 cells/mm3: without additional support
    • 40 000–70 000 cells/mm3: platelet transfusion may be considered in the preoperative and 24 h later
    • >1000 cells/mm3: no need for antibiotic prophylaxis. Some authors suggest prophylaxis if values 1000–2000 cells/mm3
    • <1000 cells/mm3: postpone dental treatment. If emergency, discuss antibiotic prophylaxis with the medical team. Hospitalisation may be required
    US National Cancer Institute, 2016
    • >60 000 cells/mm3: no additional support
    • 30 000–60 000 cells/mm3: optional transfusion for non‐invasive procedure. Consider administering preoperatively and 24 h later for surgical treatment
    • <30 000 cells/mm3: platelets should be transfused 1 h before procedure. Transfuse regularly to maintain counts >30 000–40 000 cells/mm3 until the start of healing. Consider local haemostatic agents and aminocaproic acid
    • > 2000 cells/mm3: no antibiotic prophylaxis
    • 1000–2000 cells/mm3: American Heart Association antibiotic prophylaxis recommendations (low risk). If infection present, more aggressive antibiotic therapy may be indicated
    • <1000 cells/mm3: amikacin 150 mg/m2 and ticarcillin 7 mg/kg 1 h before surgery. Repeat both 6 h postoperative
    Royal College of Surgeons of England and British Society of Disability and Oral Health, 2018 (additional comments to US National Cancer Institute guidelines)
    • >60 000 cells/mm3: major surgery may require platelet supplementation
    • 30 000–60 000 cells/mm3: liaise with oncologist. Platelet requirements also depend on extent of treatment required and need for block injections. Utilise local haemostatic techniques
    • <30 000 cells/mm3: tranexamic acid rather than aminocaproic acid
    • 1000–2000 cells/mm3: liaise with oncologist
    • <1000 cells/mm3: liaise with oncologist. An amoxicillin/clindamycin antibiotic regimen is more often recommended

    Table 12.2.2 Dental treatment planning prior to chemotherapy.

    • Care pathway
      • Early pretreatment oral assessment, including radiographs
      • Liaison with oncology team to determine the current condition of the patient, type of treatment planned and overall prognosis

    • Formulate dental treatment plan
      • An aggressive approach is required to stabilise oral health prior to cancer treatment
      • Time constraints as well as medical condition itself may require modification of the plan

    • Remove infectious and traumatic dental/oral foci
      • Surgery: teeth with dubious prognosis should be removed no less than 10 days (preferably 3  weeks) prior to commencement of cancer therapy. Remove mobile primary teeth. Evaluate need to remove partially erupted teeth and gingival operculum
      • Periodontics: professional debridement of plaque/calculus deposits to stabilise periodontal disease. Extract teeth with doubtful prognosis (periodontal pockets >6 mm)
      • Endodontics: treat decayed teeth with risk of pulpal involvement or suspicious periapical lesions early. If not possible, consider extractions. Treatment of asymptomatic chronic periapical lesions may be delayed
      • Restorative: if time permits, definitively restore carious teeth
      • Orthodontics: discontinue orthodontic treatment and remove fixed orthodontic appliances
    • Antibiotic prophylaxis/haematological support: may be warranted prior to invasive dental procedures. Liaise with the oncologist
    • Oral hygiene: establish an adequate standard of oral hygiene to meet the increasing challenges during cancer therapy
    • Dentures: if a removable prosthesis is worn, ensure it is clean and well adapted to tissue (consider soft liners)

    Table 12.2.3 Acute oral side‐effects of chemotherapy and oral care management.

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Nov 6, 2022 | Posted by in Implantology | Comments Off on Antineoplastic Agents (Chemotherapy)

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