Transcript Slide 1

Februray, 2013
The Return of My Cancer
-Emerging Effective Therapies
Jianqing Lin, MD
Why/How my cancer is back after surgery
and/or radiation?
• Undetected micro-metastatic disease (spreading) before
local treatment
• …
What are the treatment options now?
• Informed decision making to improve patient care and
survival
• Individualized care (personalized medicine): goal
• Disease state dependent
70-80%
20-30%
Death from disease
Death from co-morbidities
Prostate cancer clinical-states model
Scher et al: J Clin Oncol 26:1148-1159
Early Presentation:
• Cancer may come back in the prostate or in other parts of
the body
• May need re-biopsy to confirm (local or distant spots)
• Urinary symptoms (weak flow of urine or frequent
urination etc)
• Bone pain related to disease
• Most patients: rising PSA without symptoms
What is Prostate-Specific Antigen (PSA)?
• A glycoprotein discovered in 1970s,
• An enzyme produced by prostate gland, secreted into the male
ejaculate, regulated by male hormone (androgen receptor),
• Abnormal PSA:
– Benign conditions: BPH, prostatitis, prostate infarct or
manipulation etc. not cancer specific
– Cancer specific if prostate is removed already or radiated
– Monitoring changes of PSA is recommended after local
treatments
Natural History of a Rising PSA after surgery
(“old data”)
Time from RP to a rising PSA
2 years
Time from BCR to clinical metastases
8 years
Time from clinical metastases until
death
5 years
Life expectancy after failed surgery
15 years
Pound CR, et al. JAMA. 1999; 281:1591-1597.
Diagnostic studies and re-staging
• CAT scan and bone scan to rule out distant metastasis,
– Positive
– Negative
• MRI pelvis to determine local recurrence.
• If scans are negative, your cancer maybe still local, may
still be cured:
– Additional radiation; or
– Salvage surgery
Treatment options for recurrent prostate cancer
• Additional radiation therapy (called salvage radiation): after
surgery or seeds radiation.
• Prostatectomy (initially treated with radiation, rarely done).
• Hormone therapy
What is hormonal therapy?
• Treatment that adds, blocks, or removes hormones.
• For prostate cancer, it is to slow or stop the growth of
cancers
• Drugs may be given to block the body’s natural
hormones. Sometimes surgery is needed to remove the
gland that makes a certain hormone.
• Also called endocrine therapy, and hormone treatment.
• Approved for metastatic prostate cancer treatment
Hormonal Therapy for Prostate Cancer (traditional)
Hormone therapy
Advantages
disadvantages
note
Orchiectomy
Cost-effective
Permanent,
disfiguring
LHRH agonist
reversible
expensive
leuprolide,
goserelin
LHRH antogonist
reversible
expensive
Degarelix
(Firmagon)
Anti-androgen
therapy
Noncastrating,
improved energy,
libido, potency
Expensive,
gynecomastia
flutamide,
bicalutamide,
nilutamide, 5
reductase
inhibitors;
ketoconazole
CAB
reversible
Expensive,
increased side
effects
No evidence of
superior to LHRH
alone
CAB: Combined androgen blockade, Estrogen therapy (DES, PC-SPES): Not used now
Negative Aspects of Androgen Deprivation
• Hot flashes (Megesterol acetate, anti-depressants, phytoestrogens)
• Loss libido / erectile dysfunction (sildenafil, vardenafil, tadalafil)
• Bone mineral loss/ accelerated osteopenia (zolendronic acid,
risedronate, alendronate, calcium, vitamin D)
• Weight gain
• Changes in lipid/ glycemic metabolic profiles (?insulin sensitizing
agents, lipid lowering, high blood pressure meds)
• Anemia (erythropoeitin)
• Neuro-cognitive changes
Long Term side Effect of Androgen
Deprivation Therapy
Hyperglycemia
Insulin Resistance
Metabolic Complications of ADT
Metabolic Syndrome
Dyslipidemia
Treatment options for recurrent prostate cancer
• Additional radiation therapy (called salvage radiation): after
surgery or seeds radiation.
• Prostatectomy (initially treated with radiation, rarely done).
• Hormone therapy
• Biologic therapy (ie, Sipuleucel-T) (already treated with
hormone therapy),
Provenge Treatment Process
PROVENGE (Sipuleucel-T)—cellular immunotherapy
• Approved by FDA on 4/29/10
• Consisting of autologous peripheral blood mononuclear cells,
including antigen presenting cells (APCs), that have been
activated during a defined culture period with a recombinant
human protein, PAP-GM-CSF, an immune cell activator.
• Process: 1) standard leukapheresis to obtain PBMC 3 days prior
to the infusion date; 2) ex vivo culture with PAP-GM-CSF, the
recombinant antigen binding to and being processed by APCs; 3)
Infusion back to patient
• Extend life for 4.1 months (median)
Androgen Receptor: remains a key target for treatment
• New finding: “hormone-refractory” cancer still needs
androgen to grow  still androgen sensitive -> term changes
 castrate resistant;
• Newly approved drugs:
– Abiraterone (Zytiga):
• Oral
• Inhibits testosterone synthesis/production in testis,
adrenal glands and prostate, and cancer cells
– Enzalutamide (Xtandi):
• Oral
• pure antiandrogen/novel androgen receptor blockade
• More are coming
Treatment options for recurrent prostate cancer
• Additional radiation therapy (called salvage radiation): after
surgery or seeds radiation.
• Prostatectomy (initially treated with radiation, rarely done).
• Hormone therapy
• Biologic therapy (ie, Sipuleucel-T) (already treated with
hormone therapy),
• Chemotherapy,
Chemotherapy
•
•
•
•
More toxic but generally tolerable
Intravenously given
Need to be followed more closely
Two drugs proved to prolong life:
– Docetaxel (Texotere) first line
– Cabazitaxel (Jevtana): second line
Treatment options for recurrent prostate cancer
• Additional radiation therapy (called salvage radiation): after
surgery or seeds radiation.
• Prostatectomy (initially treated with radiation, rarely done).
• Hormone therapy
• Biologic therapy (ie, Sipuleucel-T) (already treated with
hormone therapy),
• Chemotherapy,
• Bone targeted treatment
Bone Targeted Therapies
• Vitamin D and Calcium daily
• Denosumab (Xgeva)
– To prevent bone loss, bone damage from cancer such as
fractures
– Every 4 – 6 weeks
– Mild side effects but needs to be monitored regularly
• Bisphoshonates:
– Zometa
– Similar to Xgeva
– Need to monitor kidney function
• Radiopharmaceuticals (liquid radiation):
– Alpharadin or
– samarium
RANKL: receptor activator of nuclear factor κ- B ligand
Treatment options for recurrent prostate cancer
• Additional radiation therapy (called salvage radiation): after
surgery or seeds radiation.
• Prostatectomy (initially treated with radiation, rarely done).
• Hormone therapy
• Biologic therapy (ie, Sipuleucel-T) (already treated with
hormone therapy),
• Chemotherapy,
• Bone targeted treatment
• Palliative therapy ( to lessen bone pain): Pain control,
external radiation therapy, internal radiation therapy with
radioisotopes),
Treatment options for recurrent prostate cancer
• Additional radiation therapy (called salvage radiation): after
surgery or seeds radiation.
• Prostatectomy (initially treated with radiation, rarely done).
• Hormone therapy
• Biologic therapy (ie, Sipuleucel-T) (already treated with
hormone therapy),
• Chemotherapy,
• Palliative therapy ( to lessen bone pain): Pain control, external
radiation therapy, internal radiation therapy with radioisotopes),
• Clinical trials:
– Many
– Most : new anticancer drugs (+/- radiation).
Emerging therapies for recurrent prostate cancer
• Additional radiation therapy (called salvage radiation): after
surgery or seeds radiation.
• Prostatectomy (initially treated with radiation, rarely done).
• Hormone therapy: Firmagon, Zytiga, Xtandi etc
• Biologic therapy (ie, Sipuleucel-T) (already treated with
hormone therapy),
• Chemotherapy,
• Palliative therapy ( to lessen bone pain): Pain control, external
radiation therapy, internal radiation therapy with
radioisotopes),
• Clinical trials:
– Many
– Most : new anticancer drugs (+/- radiation).
Summary
• A disease of long nature history
• Relax, don’t be panic
• Survivorship: a multimodality approach, primary care MD’s
involvement is key
• Bone is the most common metastatic site -> Bone-targeted therapy
reduce risk of fracture
• Androgen deprivation is main stay of treatment for advance PCa
but has side effects
• Androgen-AR axis remain the main target for the treatment of
PCa  novel drugs, less toxic
• Chemotherapy, active immune-therapy improve survival
• Many drugs are on the way  clinical trials are highly
encouraged
Questions and Discussion