Sipuleucel-T (Provenge) is an autologous cell-based cancer immune-therapeutic agent developed by Dendreon Pharmaceuticals, LLC. It is a personalized immune response to prostatic cancer cells. APCs are collected from the blood of the patient with prostate cancer by the process of leukapheresis. The APCs are incubated with recombinant fusion protein antigens containing both PAP and GM-CSF (by Dendreon laboratories in New Jersey). This process activates the APCs that can fight prostate cancer cells [Ref].

Indications of Sipuleucel-T (Provenge):

• Metastatic Prostate cancer:

  • It is indicated for asymptomatic/ minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

Sipuleucel-T (Provenge) dose in adults:

Note:

• For autologous use only. Premedication with oral acetaminophen 650 mg and an antihistamine (eg, diphenhydramine 50 mg) half-hour before the infusion is required.
• Do not infuse until confirmation of product release has been received from the company.

Sipuleucel-T (Provenge) dose for the treatment of metastatic Prostate cancer:

• Each intravenous dose contains ≥50 million autologous CD54+ cells (obtained through leukapheresis) activated with PAP-GM-CSF.
• Administer doses at 14 days intervals for a total of 3 doses. If unable to receive a scheduled infusion, an additional leukapheresis procedure will be necessary before continuing a course of treatment.

Sipuleucel-T (Provenge) dose in Childrens:

Not recommended for use in children.

Pregnancy Risk Category: X

• Studies on animal reproduction have not been completed.
• It is not recommended to be used in women.

Use Sipuleucel T while breastfeeding

• Not recommended for use by women

Dose adjustment in renal disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Sipuleucel-T (Provenge) Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Common Side Effects of Sipuleucel-T (Provenge):

Note: Initial infusion-related events usually present within the first 24 hours after administration.

• Central Nervous System:

  • Chills
  • Fatigue
  • Headache
  • Dizziness
  • Pain

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Constipation

• Hematologic:

  • Anemia

• Hypersensitivity:

  • Severe Infusion Related Reaction

• Neuromuscular & Skeletal:

  • Back Pain
  • Myalgia
  • Weakness

• Miscellaneous:

  • Fever
  • Citrate Toxicity

Uncommon Side Effects of Sipuleucel-T (Provenge):

• Cardiovascular:

  • Hypertension
  • Hemorrhagic Stroke

• Dermatologic:

  • Diaphoresis
  • Skin Rash

• Gastrointestinal:

  • Anorexia
  • Acute Ischemic Stroke

• Genitourinary:

  • Hematuria

• Neuromuscular & Skeletal:

  • Musculoskeletal Pain
  • Muscle Spasm
  • Neck Pain
  • Tremor

• Renal:

  • Hematuria

• Respiratory:

  • Flu-Like Symptoms
  • Dyspnea

Contraindication to Sipuleucel-T (Provenge):

The manufacturer's labeling does not list any contraindications.

Warnings and precautions

• Infusion reaction

  • There are some symptoms such as headaches, dizziness and fatigue, chills, rigor or fever, bronchospasms, dyspneasm, hypoxia/hypotension (tachycardia), syncope, myalgias.
  • Infusion reactions can be mild to moderate in the first infusion. The severity of the reaction is usually greater with the second and third infusions.
  • Premedication with intravenous antihistamine, acetaminophen and low dose meperidine is used to treat symptoms.

• Events that are thromboembolic:

  • Patients with risk factors should exercise caution when sipuleucel T infusion is performed.

• Cerebrovascular diseases:

  • Cerebrovascular events, such as hemorhagic or ischemic strokes, can happen.

• Cardiovascular disease

  • Patients with cardiac conditions should be closely monitored during infusions as it could cause myocardial injury.

• Pulmonary disease

  • Patients with pulmonary problems should be closely monitored during infusions.

Sipuleucel-T: Drug Interaction

Monitoring parameters:

Monitoring is required for:

• infusion reaction during or 30 minutes after infusion
• for patients with cardiovascular and pulmonary disease during therapy
• thromboembolic and vascular events.

How to administer Sipuleucel-T (Provenge)?

Only intravenous for autologous purposes:

• Before infusion, the patient's identity is verified by matching the patient identifiers on both the infusion bag or the "Final Product Desposition Notification" (before infusion).
• After the company has confirmed product release, do not infuse. 
• You should keep the sealed infusion bag in the shipping box with the insulated polyurethane container until you are ready to administer it.
• You should inspect the bag for leakage and damage. Mix the infusion gently.
• If there is a clot, it should be stopped. If the infusion is not expired, it should be stopped immediately.

Only for IV Infusion

• Allow the bag to infuse for at least one hour.
• Do NOTUse a cell filter to infuse. Acute symptoms can be managed with intravenous antihistamine, Acetaminophen, or low-dose meperidine.
• The infusion bag should not be left at room temperature if it is interrupted.
• However, if the bag remains at room temperature for more than 3 hours, therapy can be restarted. It is important to observe for at least half an hour after infusion.

Mechanism of action of Sipuleucel-T (Provenge):

• An autologous cellular immunotherapy that stimulates an immune response against an antigen expressed in most prostate carcinoma tissues.
• Leukapheresis is a procedure that collects peripheral blood from patients for isolating peripheral mononuclear cells (PBMCs).
• This is done three days before infusion. For the production of antigen-presenting cells (APC) precursors, peripheral blood mononuclear cell lines are used.
• These cells consist of CD54-positive cells and dendritic cells.
• In vitro activation of the antigen-presenting cells is then done with a recombinant human fusion proteins, PAP-GMCSF (also known as PA2024).
• This protein is composed of an antigen-specific antigen for prostate cancer, prostatic acids phosphatase, (PAP), linked to granulocyte - macrophage colony-stimulating factors (GM-CSF) in a culture dish for 40 hours.
• Sipuleucel T is re-infused into patients to instill T-cell immunity against tumors that express PAP.

Sipuleucel-T Brand Names (International):

• Provenge

Sipuleucel-T Brand Names in Pakistan:

No Brands Available in Pakistan.