What are the side effects of the AAVD (Adriamycin (doxorubicin), Vinblastine, Dacarbazine) protocol?

Side Effects of AAVD (Adriamycin, Vinblastine, Dacarbazine) Protocol

The AAVD protocol can cause significant cardiotoxicity, myelosuppression, neurological toxicity, and pulmonary complications, with cardiotoxicity being the most concerning long-term effect, especially in pediatric and young adult patients. 1

Major Side Effects

Cardiovascular Toxicity

• Cardiotoxicity: Doxorubicin (Adriamycin) is associated with dose-dependent cardiomyopathy that can lead to congestive heart failure 2, 3
  • Risk increases with cumulative doses exceeding 300 mg/m² 1
  • Particularly concerning in children and adolescents, especially when combined with chest radiation 1
  • Monitoring: Ejection fraction evaluation recommended before treatment 1
  • Long-term surveillance: Every 2-5 years depending on risk level 1

Hematologic Toxicity

• Leukopenia (granulocytopenia): Most common and dose-limiting adverse reaction 4
• Anemia and thrombocytopenia (myelosuppression) 4

Neurological Effects

• Peripheral neuropathy: Numbness of digits, loss of deep tendon reflexes 4
• Other neurological effects: Mental depression, headache, convulsions 4
• Eighth cranial nerve damage: May cause vestibular and auditory damage resulting in partial or total deafness (temporary or permanent), dizziness, nystagmus, and vertigo 4

Pulmonary Toxicity

• Associated with bleomycin (though not part of AAVD specifically)
• Pulmonary function tests recommended before treatment 1
• Monitoring at entry into long-term follow-up and as clinically indicated 1

Gastrointestinal Effects

• Nausea and vomiting: Usually controllable with antiemetic agents 4
• Constipation, anorexia, abdominal pain 4
• Oral complications: Mouth vesiculation, pharyngitis 4
• Gastrointestinal bleeding: Hemorrhagic enterocolitis, rectal bleeding 4

Dermatologic Effects

• Alopecia: Very common but often reversible 4
• Skin vesiculation: Particularly with extravasation during IV administration 4

Long-Term Complications

Secondary Malignancies

• Risk of subsequent neoplasms, particularly with radiation therapy 1
• Surveillance recommendations:
  • Breast cancer screening: Beginning at age 25 and 8 years after radiation therapy 1
  • Colorectal cancer screening: Every 5 years beginning at age 30 and 5 years after radiation therapy 1
  • Thyroid cancer screening: Annual monitoring if thyroid was in radiation field 1
  • Skin cancer screening: Annual monitoring 1

Thyroid Dysfunction

• 5-year cumulative incidence: 2% ± 1%
• 9-year cumulative incidence: 27.9% ± 4.5% 5
• Subclinical hypothyroidism is the most common thyroid abnormality 5

Hypertension

• Observed in approximately 31% of patients 5
• Risk factors: Young age and obesity at time of treatment 5

Special Considerations

Age-Related Concerns

• In patients >60 years, bleomycin should be discontinued after the second chemotherapy cycle due to increased toxicity risk 1

Fertility Concerns

• Fertility preservation recommended before treatment with alkylating agents or pelvic radiation 1
• Oophoropexy should be considered to preserve ovarian function in premenopausal women if pelvic radiation is planned 1

Monitoring Recommendations

1. Cardiac monitoring:

   • Baseline evaluation of ejection fraction
   • Regular follow-up every 2-5 years based on risk level 1

2. Complete blood counts:

   • Regular monitoring during treatment to manage myelosuppression

3. Thyroid function:

   • Annual monitoring, especially if radiation was administered to neck/chest 1

4. Long-term cancer surveillance:

   • As outlined above for secondary malignancies

The AAVD protocol requires careful monitoring and management of side effects, with particular attention to cardiotoxicity given its potential for long-term morbidity and mortality.