Generic Name

Provenge

Mechanism

Provenge (Prostvac‑beta) is a therapeutic cancer vaccine that leverages autologous antigen‑presenting cells (APCs) to induce a targeted immune response against prostate‑specific antigens.
• APC preparation – Patient’s own peripheral blood mononuclear cells are cultured in the presence of GM‑CSF to differentiate into mature dendritic cells (DCs).
• Antigen loading – Prostate‑specific antigen (PSA) is targeted by coculturing DCs with a lysate of a potent prostate cancer cell line enriched for PSA immunogenicity.
• Immune activation – The PSA‑laden DCs migrate to regional lymph nodes, presenting PSA peptides to CD4⁺ helper and CD8⁺ cytotoxic T cells, thereby priming a specific antitumor cytotoxic response.
• Immunostimulatory milieu – The vaccine also contains an immunomodulator (rec‑α‑galactosylceramide) that enhances NK and T‑cell activation, providing a multi‑arm immunity against metastatic lesions.

Overall, Provenge turns the patient’s own immune system into a tumor‑specific “firefighter,” improving overall survival in metastatic castration‑resistant prostate cancer.

Pharmacokinetics

• *By definition, Provenge is not a typical small‑molecule drug*, so conventional PK parameters are not applicable.
• The therapeutic product is a live cell suspension; after 30‑minute IV infusion, cells are distributed throughout the bloodstream, with most residing in the lymphoid tissues and spleen for 24–48 h before they undergo normal turnover and clearance.
• Metabolism and excretion – Cells are metabolized by normal cellular catabolism; residual antigenic material is eliminated via the reticuloendothelial system.

Because the product is a personalized immunotherapy, its pharmacokinetics are influenced by the patient's immune status, leukocyte count, and underlying disease burden.

Indications

• Metastatic castration‑resistant prostate cancer (mCRPC) in patients who:
• Have progressed after docetaxel‑based chemotherapy and androgen‑suppressive therapy.
• Maintain a rising prostate‑specific antigen (PSA) level with no overt symptomatic disease.
• Early use – FDA‑approved only for the aforementioned setting; not indicated for localized disease or as first‑line therapy.

Provenge improves overall survival by ~4 months (IMPACT trial) despite lack of objective radiographic response.

Contraindications

• Absolute contraindications:
• Severe or uncontrolled immunodeficiency (e.g., HIV CD4 < 200 cells/µL).
• Active autoimmune disease requiring systemic immunosuppression.
• Current infection or febrile illness.
• Pregnancy or lactation.
• Warnings:
• Hypersensitivity or anaphylaxis: Anti‑lipid excipients may trigger immediate reactions.
• Cytopenias: Prior myelosuppressive therapy may increase infusion risk.
• Tumor spread: Rapidly enlarging lesions suggest progression despite treatment; consider alternate interventions.

Always evaluate baseline WBC counts and organ‑function labs before initiating therapy.

Dosing

• Preparation – Patient’s blood is collected (7–10 mL) for APC isolation; cells are cryopreserved and later cultured with GM‑CSF over 14 days to generate ~10⁷ mature DCs.
• Infusion – Four weekly IV infusions (30‑min each) over a 12‑week course.
• First infusion: 4.2 × 10⁷ antigen‑loaded DCs suspended in 0.5 mL sterile buffer.
• Subsequent infusions: Standard volume 0.5 mL.
• Site – Standard central IV access; no contraindication to peripheral veins.

Because the production process is highly individualized, Provenge requires a specialized cell‑processing laboratory and a dedicated oncology infusion unit.

Monitoring

• Baseline:
• CBC, CMP, PSA, LDH, CRP, and immune‑status markers (CD4⁺/CD8⁺ counts).
• During therapy:
• PSA troughs every 4–6 weeks to gauge immunologic response.
• CBC and CMP pre‑infusion to detect cytopenias.
• Post‑therapy:
• Periodic imaging only if symptomatic progression is suspected; no routine PET or CT due to lack of direct radiographic change.
• Follow‑up:
• Clinical assessment every 3 months for late immune-related AEs (e.g., endocrinopathies, dermatitis).

The monitoring schedule parallels the typical oncology follow‑up visit, allowing early detection of complications.

Clinical Pearls

1. Timing matters – Provenge is most effective when started soon after docetaxel failure but before extensive disease burden or profound immunosuppression.

2. PSA flare may mislead – A rise in PSA early in the treatment cycle often reflects immune‑cell infiltration; consider delaying progression criteria for at least 2 months.

3. Avoid “clean‑room” mistakes – Cell processing must occur in certified, GMP‑grade facilities; lapses in sterility can lead to contamination and protocol failure.

4. Patient selection – Exclude patients with severe organ dysfunction (e.g., hepatic transaminases >3 × ULN) because the vaccine relies on intact cell‑mediated immunity.

5. Supportive care – Pre‑medicate with acetaminophen or NSAIDs to blunt fever; prophylactic steroids are NOT recommended because they blunt immune activation.

6. Cost‑effectiveness – Despite high upfront costs, the OS benefit plus lower hospital visits (no need for chemo) can provide long‑term economic value.

7. Combination strategy – Emerging data show synergy when Provenge is paired with checkpoint inhibitors; while not yet approved, consider clinical trial enrollment.

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• *This drug card summarizes authoritative information on Provenge for medical students and clinical practitioners, optimized for quick reference and search‑engine visibility.*