sipuleucel-T

sipuleucel-T

Provenge

Pharmacologic class: Autologous cellular immunotherapy

Therapeutic class: Antineoplastic

Pregnancy risk category None

Action

Not clearly understood. Induces an immune response targeted against prostatic acid phosphatase (PAP), an antigen expressed in most prostate cancers. During ex vivo culture with PAP-GM-CSF (granulocyte macrophage-colony stimulating factor), APCs (tumor suppressor genes) take up and process the recombinant target antigen into small peptides that are then displayed on the APC surface.

Availability

Suspension for injection: 50 million autologous CD54+ cells activated with PAP-GM-CSF suspended in 250 ml of lactated Ringer's injection in infusion bag

Indications and dosages

Asymptomatic or minimally symptomatic metastatic castration-resistant (hormone refractory) prostate cancer

Adults: 50 million autologous CD54+ cells activated with PAP-GM-CSF in lactated Ringer's solution by I.V. infusion over approximately 60 minutes; give three complete doses at approximately 2-week intervals

Contraindications

None

Precautions

Use cautiously in:
• cardiac or pulmonary conditions
• infusion reactions
• concurrent use of chemotherapy or immunosuppressive therapy.

Administration

• Be aware that drug is for autologous use only.
• Don't infuse drug until confirmation of product release has been received from manufacturer.
• Premedicate with acetaminophen and an antihistamine such as diphenhydramine approximately 30 minutes before infusing drug, to prevent infusion reactions.
• Administer by I.V. infusion only. Don't use a cell filter.
• Gently mix and resuspend bag's contents; inspect for clumps and clots. Small clumps of cellular material should disperse with gentle manual mixing. Don't administer if bag leaks during handling or if clumps remain in bag.

Interrupt or slow infusion for acute infusion reactions. If infusion must be interrupted, don't resume infusion if infusion bag is held at room temperature for more than 3 hours.
• Observe patient for at least 30 minutes after each infusion.
• Be aware that if patient is unable to receive scheduled infusion for any reason, patient will need to undergo an additional leukapheresis procedure if course of treatment is to be continued.
• Be aware that drug isn't recommended for patients with visceral disease and less than 6-month life expectancy.

Adverse reactions

CNS: headache, dizziness, fatigue, paresthesia, asthenia, insomnia, tremor, cerebrovascular events

CV: hypertension

GI: nausea, vomiting, diarrhea, constipation, anorexia, oral paresthesia

GU: hematuria, urinary tract infection

Hematologic: anemia

Musculoskeletal: back pain, joint and muscle ache, extremity pain, muscle and bone pain, neck pain, muscle spasms

Respiratory: dyspnea, upper respiratory tract infection, cough

Skin: rash

Other: chills, fever, pain, citrate toxicity, influenza-like illness, peripheral edema, hot flushes, chest pain, sweating, weight loss, risk of transmitting infectious diseases, acute infusion reactions

Interactions

None

Patient monitoring

Continue to observe patient for infusion reaction after each infusion.

Monitor patient for cerebrovascu-lar events, including hemorrhagic and ischemic strokes.

Patient teaching

• Inform patient that each infusion is preceded by a leukapheresis procedure approximately 3 days before drug infusion and that it's important to maintain all scheduled appointments and arrive at each appointment on time, because the leukapheresis and infusions must be appropriately spaced and drug expiration time must not be exceeded.
• Explain importance of premedication before starting infusion.

Instruct patient to immediately report signs and symptoms of acute infusion reactions (such as fever, chills, fatigue, breathing problems, dizziness, high blood pressure, nausea, vomiting, headache, or muscle aches).
• Instruct patient to promptly notify prescriber if fever or swelling or redness around catheter site occurs, because these could indicate an infected catheter.
• Instruct patient to tell prescriber about all drugs he's taking, especially immunosuppressants.
• As appropriate, review all other significant and life-threatening adverse reactions mentioned above.

References in periodicals archive ?
In April 2010, the FDA approval of Sipuleucel-T (PROVENGE, manufactured by Dendreon Corporation), a dendritic cell vaccine, gave a push to the concept of DCT.
A priority at Dendreon is to explore the use of sipuleucel-T in earlier stages of prostate cancer and in combination with other agents that may enhance the immune response and patient outcomes.
15] The phase III IMPACT study, in which 512 patients with mCRPC were randomized (2:1) to receive sipuleucel-T or placebo, has shown a survival advantage in the active treatment group (sipuleucel-T, 25.
A further drug sipuleucel-T has also been shown to extend life in the two-year period.
The Centers for Medicare and Medicaid Services has determined that the evidence supports the conclusion that the prostate cancer vaccine sipuleucel-T, better known as Provenge, is an effective therapy and should be covered for Medicare beneficiaries.
In March, an FDA advisory panel gave sipuleucel-T the thumbs-up, but the agency decided to delay approval pending the completion of a large trial in men with prostate cancer.
The approval of sipuleucel-T would open a new front on the war on cancer because although it would be the third cancer vaccine approved, it is the first that is therapeutic.
If approved, sipuleucel-T will be marketed as PROVENGE.
Abstract #34: Randomized Phase II Trial Evaluating the Optimal Sequencing of Sipuleucel-T and Androgen Deprivation Therapy (ADT) in Patients with Biochemically-Recurrent Prostate Cancer (BRPC): A Phase II sequencing study evaluating PROVENGE followed by ADT or ADT followed by PROVENGE in men with biochemically-recurrent prostate cancer showed a prime-boost immune response effect based on antigen presenting cell activation patterns, and an analysis of serum samples indicated that there were no differences between the arms in cellular or humoral immune responses.
The first cancer vaccine Sipuleucel-T (Provenge(tm)) was licensed last year for use in prostate cancer patients unresponsive to hormone treatment.
On the other hand, the New England Journal of Medicine recently published an editorial about sipuleucel-T (Provenge), the new immunomodulating vaccine for end-stage prostate cancer that on average extends life by 4 months at the cost of nearly $95,000 per patient (N.
Monday, October 11, 2010, 12:30 - 13:30 CEST - "Survival Results of the IMPACT Trial of Sipuleucel-T for Advanced Prostate Cancer.