A 4-year-old boy presents with a unilateral abdominal mass and hematuria. Imaging confirms a Wilms tumor without metastases (Stage III). After nephron-sparing surgery and staging, he is enrolled in a multimodal chemotherapy protocol. Which drug is the cornerstone of the first-line regimen for Wilms tumor?

Explanation

## First-Line Chemotherapy for Wilms Tumor **Key Point:** Vincristine is the backbone of all standard Wilms tumor chemotherapy regimens, used in combination with actinomycin D and doxorubicin (VAD protocol). ### Standard Regimen (COG Protocol) The most commonly used first-line combination is: - **Vincristine** — microtubule inhibitor; given weekly or biweekly - **Actinomycin D** — DNA intercalator; given every 5 days - **Doxorubicin** — topoisomerase II inhibitor; given every 5 days This VAD (or sometimes EE-4A) regimen is used for: - Intermediate-risk and high-risk tumors - Neoadjuvant therapy (preoperative) - Adjuvant therapy (postoperative) **High-Yield:** Vincristine is ALWAYS included in Wilms tumor chemotherapy. It is the single most important agent and is never omitted from standard protocols. ### Why Each Agent? | Agent | Role | Toxicity Profile | | --- | --- | --- | | **Vincristine** | Backbone; essential in all regimens | Peripheral neuropathy, constipation | | **Actinomycin D** | Synergistic with vincristine | Hepatotoxicity, myelosuppression | | **Doxorubicin** | Added for high-risk disease | Cardiotoxicity, cumulative dose limit | | **Etoposide** | Reserved for relapsed/refractory disease | Myelosuppression, secondary malignancy | **Clinical Pearl:** The choice between VAD (3-drug) vs. VA (2-drug) depends on risk stratification: - **Low-risk:** Vincristine + Actinomycin D (VA) may suffice - **Intermediate/High-risk:** Full VAD regimen is standard **Mnemonic:** **VAD = Vincristine, Actinomycin D, Doxorubicin** — the classic Wilms tumor triple therapy. [cite:Park 26e Ch 12]