What is the recommended chemotherapy approach for extensive basal cell carcinoma?

Chemotherapy for Extensive Basal Cell Carcinoma

Hedgehog pathway inhibitors (vismodegib or sonidegib) are the recommended first-line systemic therapy for extensive basal cell carcinoma that is locally advanced or metastatic, particularly when surgery and radiation are not feasible options. 1

Treatment Algorithm for Extensive BCC

First-Line Systemic Therapy:

• Hedgehog pathway inhibitors:
  • Vismodegib 150mg orally once daily (FDA-approved for both locally advanced and metastatic BCC) 2
  • Sonidegib (FDA-approved for locally advanced BCC) 3

Second-Line Options (if hedgehog inhibitors fail or are contraindicated):

• Platinum-based chemotherapy regimens 1
• Clinical trial enrollment
• Best supportive care for symptom management 1

Clinical Considerations

Patient Selection:

• Candidates for hedgehog pathway inhibitors include patients with:
  • Metastatic BCC
  • Locally advanced BCC that has recurred following surgery
  • BCC where surgery would result in substantial morbidity/deformity
  • BCC in patients who are not candidates for surgery or radiation 1

Efficacy:

• Vismodegib: 30-33% objective response rate in metastatic BCC; 43-48% in locally advanced BCC 1
• Sonidegib: 8-17% response rate in metastatic BCC; 44-58% in locally advanced BCC 1
• Complete responses occur in approximately 21% of locally advanced BCC cases with vismodegib 1

Important Adverse Effects to Monitor:

• Muscle spasms (most common)
• Dysgeusia (taste disturbance)
• Alopecia
• Weight loss
• Fatigue
• Elevated creatine kinase 4

Management of Adverse Effects:

• Treatment interruptions for up to 8 weeks may be needed for intolerable adverse reactions 2
• Approximately 36% of patients discontinue treatment due to adverse events 1
• Protocol modifications including dose reductions and treatment interruptions can help manage side effects while maintaining disease control 4

Special Considerations

Resistance:

• Resistance to hedgehog pathway inhibitors can develop, limiting duration of response (median duration: 7.6-9.5 months) 1
• Cross-resistance between vismodegib and sonidegib has been observed 1

Pregnancy Concerns:

• Hedgehog pathway inhibitors are embryotoxic and teratogenic
• Verify pregnancy status before initiating treatment
• Effective contraception required during treatment and for 24 months after final dose for females 2
• Males should use condoms during treatment and for 3 months after final dose 2

Follow-Up:

• Regular monitoring is essential with complete skin examinations every 6-12 months for at least 2 years 1
• Patients with BCC have a 10-fold increased risk of developing another BCC within 5 years 1

Multidisciplinary Approach

For extensive BCC cases, management by a multidisciplinary tumor board is recommended to determine the optimal treatment strategy, particularly for metastatic disease or cases with significant morbidity 1.

While surgery with or without radiation therapy remains the gold standard for most BCC cases, hedgehog pathway inhibitors have revolutionized treatment for extensive disease where traditional approaches are not feasible or effective 5, 6.