GOOD NEWS!!! New Regimens and Therapeutic Agents in the Pipeline; a Visit with my Oncologist.

Every six months, I have an appointment with my oncologist at the Moffitt Cancer Center, on the campus of the University of South Florida, in Tampa. Moffitt is a designated National Cancer Institute (NCI, National Institutes of Health, my former employer) Comprehensive Cancer Center, a highly-sought-after distinction. My oncologist had been highly recommended to me by former program directors at the National Cancer Institute. I am always grateful for the opportunity to discuss with him not only my own situation but to learn about new potential therapies in various stages of clinical trials.

One such earlier appointment is chronicled in the My Story section of this website, November 25th, 2009. At that time, we had discussed the positive results seen in prostate cancer patients treated with either Provenge or abiraterone. In 2011, both of these drugs have now received FDA approval. This has affected my own prognosis dramatically. When a prostate cancer patient becomes resistant (refractory) to standard hormonal therapy and the cancer metastasizes, the next chemotherapy option is usually taxotere and prednisone. Serious side effects often accompany taxotere / prednisone treatment. I am currently in my 5th year on hormonal therapy and my oncologist informed me that I could be maintained in this non-symptomatic manner for years before I would become refractory. Looking ahead, I did not look forward to chemotherapy with taxotere. But with the availability of new therapies, my own “treatment schedule” had changed. After hormonal therapy, I would probably be placed sequentially on Provenge and/or abiraterone, both of which are effective and well tolerated. All in all, the goal of prostate cancer patients like myself is simply to “buy quality time” unless God chooses to heal us directly (which is always possible). I am now nearly 70 years of age. I just may out-live this disease. God uses many methods and the God-given talents of many people to heal or stabilize our diseases.

To make the situation more optimistic, the following are several new potential therapies in various stages of clinical trials. [For an excellent overview of the various phases (I, II, III) of clinical testing required of a drug to obtain FDA approval, see the Johns Hopkins Health Alert related to prescription drugs,  posted March 10, 2009. Phase I studies focus mainly on biological effects, including harmful side effects of the drug on the human body; Phase II studies attempt to demonstrate whether the drug provides a safe benefit in treating people with a specific condition; and, Phase III studies better define the benefits, risks and side effects of the drug.]

1) As a follow-up to current hormonal (androgen deprivation) therapy, Millennium and its parent company Takeda Pharmaceutical, are developing TAK-700 (future name to be Ortoronel), a selective, oral, non-steroidal androgen synthesis inhibitor. In preclinical studies TAK-700 has been shown to bind to and inhibit the enzyme 17,20-lyase 1 in the testes and adrenal glands. TAK-700 is now in Phase III clinical trials in metastatic, castration-resistant prostate cancer and studies are planned for patients who have failed taxotere as well. For information, see the “New Prostate Cancer Info Link,

2) Another new drug is Exelexis’ capozantinib (XL184) which has already received FDA orphan drug approval for the treatment of certain thyroid cancers.  Optimistic reports for XL 184 came from Phase II clinical trials on patients with metastatic  prostate cancer who had failed hormonal therapy. In a group of patients, 95% achieved complete or partial resolution of metastatic bone lesions. Bone scans taken after treatment could not detect any metastases on patients whose previous scans demonstrated substantial cancer spread. The pain accompanying cancer metastasis to the bone was also alleviated.  While XL184 was well tolerated and demonstrated substantial activity against bone metastases, similar dramatic activity against the primary tumor was observed in only six (6) of the 100 patients. Therefore it is too early to predict whether XL184 will extend survival.  XL184, a member of a class of drugs known as tyrosine kinase inhibitors, is designed to work as follows. In cells, MET (otherwise known as hepatocyte growth factor, HGF) and vascular endothelial growth factor type-2 (VEGF2) are both proteins produced by cells. MET is involved in tumor cell proliferation, invasion and tumor spread as well as bone metastasis; while VEGF-2 stimulates angiogenesis, the growth of new blood vessels to feed the tumors. Drugs like XL184 have the potential to “switch off” processes (initiated by tyrosine kinases) within a cell that promote tumor growth.  MET and VEGF also play roles in the function of healthy bone cells such as osteoblasts and osteoclasts. “Switching off” MET and VEGF  simultaneously may block the progression of bone lesions.  While Phase III trials are planned, phase II trials are still recruiting prostate cancer patients in ten states; see http://www.clinicaltrials.gov/ct2/show/NCT00940225.  XL184 is also being evaluated against other tumors such as ovarian.  (Reference: Dr. Mark Scholz, in PCRI Insights, May, 2011, Vol. 14, No. 2, pp.12-14).

3) A third drug to watch for is Yervoy (previously known as ipilimumab) from Bristol-Myers-Squibb. Yervoy, a human  monoclonal antibody, is a cancer immunotherapy that has previously received FDA approval in March, 2011 to treat melanoma.  The Yervoy antibody targets cytotoxic T lymphocyte antigen-4, preventing the antigen from interacting with its ligands and thereby activating the patient’s own immune system by causing these T-cells to potentially combat tumor cells.  More simply, Yervoy blocks a switch that turns off an anti-tumor cellular response. Therefore, Yervoy is an agent that “blocks a blocker” thereby aiding the immune system to fight the tumor.  It should also be mentioned that nearly 13% of patients taking Yervoy had severe autoimmune reactions, consisting of mostly of fatigue and severe skin and gastrointestinal reactions.  The FDA is allowing Yervoy to be evaluated against prostate cancer.

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