CORT Metastatic Prostate Cancer Symposium

The Center for Oncology Research & Treatment will host a Symposium titled “Progress in Treatment of Metastatic Prostate Cancer“ at Medical City Dallas Hospital on Wednesday, November 18, 2009, 6:30-8:30 PM.  Featured speakers will include urologic, medical, and radiation oncologists, who will review their perspectives on management issues of patients with metastatic disease.  Treatment with hormonal agents, chemotherapy, radiation, and investigational therapies will be discussed.  Here is the conference notice:

Prostate Cancer Symposium
Progress in Treatment of Metastatic Prostate Cancer

With
Barry C. Mirtsching, MD
Conference Chair
Medical Oncology
Center for Oncology Research & Treatment
Dallas, TX

Wilson Hernandez, MD
Radiation Oncology
Urology Clinics of North Texas
Dallas, TX

Elie Benaim, MD
Urologic Oncology
Dallas Urology Associates
Dallas, TX

Located at Medical City Dallas, City Hall in Bld. E
7777 Forest Lane, Dallas TX 75230

Wednesday, November 18, 6:30-8:00 PM

Please call to RSVP:
972-566-5588

New Treatment for Her-2+ Metastatic Breast Cancer Opens at CORT

CORT has opened the Wyeth 3144A2 3005 WW Study testing the oral her-2 inhibitor, neratinib, in combination with paclitaxel (Taxol), versus standard therapy with trastuzumab (Herceptin) in combination with paclitaxel, for first-line treatment of her-2+ metastatic breast cancer. 

Neratinib is an oral anti-her-1/her-2 drug with demonstrated efficacy in metastatic her-2 positive breast cancer.  The safety studies have demonstrated acceptable and manageable toxicity of neratinib, including rash and occasional loose stools or diarrhea being most common.  As with other her-2 inhibiting drugs, neratinib may lower the cardiac ejection fraction, so serial monitoring of cardiac function is routine.  The Phase III study will compare the efficacy and tolerability of paclitaxel with either oral neratinib or trastuzumab (a monoclonal antibody against her-2 protein, given IV).

The potential advantages of neratinib include improved convenience (and possibly improved safety).  The drug is given orally.  

For more information about this study, visit our website at www.CORTPA.com, or contact a Research Coordinator at 972-566-5588.  

Patients with her-2+ breast cancer may also be eligible for other studies and treatment at CORT, including non-study therapy.  The principle investigator at CORT is Dr. Barry Mirtsching.  He has personally conducted over 200 trials in cancer therapy over 16 years, many in breast cancer management.  Experience in both trial and non-trial breast cancer management benefits patients by producing better treatment outcomes.  Care at CORT is individual and personal, with adequate time for problem-solving and direct contact with the physician.

STRIDE Breast Cancer Study Testing Stimuvax Cancer Vaccine Open at CORT

CORT has opened the STRIDE study for first-line treatment of metastatic, hormone-receptor positive breast cancer.  The study will test standard anti-estrogen therapy in combination with a vaccine placebo, versus standard anti-estrogen therapy with the Stimuvax cancer vaccine.  The press release regarding this study is posted below.

For more information about this study, or to schedule appointments for evaluation and treatment of metastatic breast cancer, visit the CORT website at www.CORTPA.com, or call 972-566-5588 and ask to speak with a Patient Care Coordinator or CORT Research Nurse. 

STRIDE Press Announcement:

24 Jun 2009 – Merck KGaA announced the initiation of its global Phase III clinical study of the therapeutic cancer vaccine Stimuvax® (BLP25 liposome vaccine, L-BLP25) in patients with advanced, inoperable breast cancer. The STRIDEa study will determine if Stimuvax can extend progression-free survival in patients treated with hormonal therapy who have hormone receptor-positive, locally advanced, recurrent or metastatic breast cancer. Overall survival, quality of life, tumor response and safety will also be assessed in this study. The STRIDE study will be supervised by an expert Steering Committee and is sponsored by Merck, which is leading the development of Stimuvax.
STRIDE will enroll more than 900 patients with advanced breast cancer at an estimated 180 sites in over 30 countries – within North America, Europe, Asia and Australia; the Principal Investigator is Dr Lawrence Shulman, Chief Medical Officer and Senior Vice President for Medical Affairs, Dana-Farber Cancer Institute, Boston, USA.
 
Stimuvax is an investigational therapeutic cancer vaccine designed to stimulate the body’s immune system to identify and target cancer cells that express MUC1, an antigen commonly expressed in breast cancer as well as in other common cancer types such as non-small cell lung cancer (NSCLC), multiple myeloma, and colorectal, prostate and ovarian cancers.
 
The Phase III program for Stimuvax was initiated following results from a randomized Phase IIb study of 171 patients with inoperable stage IIIb NSCLC, in which Stimuvax showed a trend towards extending median overall survival from 13.3 months for patients receiving best supportive care (BSC) to 30.6 months for patients receiving Stimuvax plus BSC. Reported side effects included mild-to-moderate flu-like symptoms, gastrointestinal disturbances and mild injection-site reactions. A further long-term safety analysis in 16 patients receiving prolonged treatment with Stimuvax from 2 to 8.2 years showed the most common treatment-related adverse events were injection-site reactions (ISRs) with no evidence of autoimmune reactions. These data also show that the occurrence of ISRs decreased with long-term therapy (>1 year).

Study Tests Extension of Anti-Her-2 Therapy Beyond Herceptin for Early Stage Breast Cancer Patients

The Wyeth Study 3144A2-3004-WW testing a new oral drug, neratinib, is active and enrolling at CORT.  This study is open to early-stage, her-2 positive patients who have completed adjuvant therapy and one year of trastuzumab (Herceptin), the current standard-of-care.  Such patients are generally followed without further treatment.  The relapse risk of these patients is reduced by the one year of trastuzumab (see Figure 1: Analysis of Relapse Risk over Time, adapted from Herceptin Product Literature).  

As can be seen from the figure, the AC>TH arm has a lower risk of annual recurrence that begins during the first year (the time the treatment with trastuzumab is given), and that benefit continues, when compared to patients treated with chemotherapy alone (AC>T).  However, the risk for recurrence does rise in the trastuzumab-treated patients after the therapy is completed at one year, and that risk remains increased for another 2 or 3 years, at approximately 4.9% per year. 

To address that continued risk, studies testing the extension of anti-her-2 therapy are being conducted.  The Wyeth study at CORT tests the oral anti-her-2 drug neratinib (HKI-272).  The study is a randomized comparison of neratinib versus a neratinib placebo, given daily by mouth for one year.  Neratinib may reduce cardiac function (similar to other her-2 blockers), so function must be monitored.  Other risks include rash, diarrhea, and nausea.  Based on experience with the drug to date, these risks can be managed with supportive care medication and/or dose reduction in most circumstances. 

Patients who have completed one year of adjuvant therapy with trastuzumab (Herceptin), and who are within 2 years of completion of that therapy are eligbile for the Wyeth study at CORT. 

For more information about this study, or to schedule a consultation about management of breast cancer, call 972-566-5588, and ask to speak with a Patient Care Coordinator.   Additional information about this study, and directions to the office are located at: www.CORTPA.com.

Prostate Cancer Immunotherapy Study Open at CORT

CORT is actively enrolling patients with metastatic hormone-refractory (androgen-independent) prostate cancer in the BMS 184-043 study of ipilimumab (versus placebo).   The study is open to patients who have at least one bone metastasis, and who have progressed after prior therapy with docetaxel (Taxotere).  Other inclusions and exclusions are required.   Ipilimumab is a monoclonal antibody that inhibits the cellular function of CTLA-4.  CTLA-4 inhibits the T-cell immune response to cancer cells, and by blocking this molecule, T-cells are activated.  Ipilimumab is in clinical development in melanoma (also at CORT).  Responses in both metastatic prostate cancer and melanoma have been demonstrated.  The drug is given every 3 weeks IV for four treatments (induction).  Thereafter, for patients with improvement or stability in their disease, the drug is continued every 3 months (maintenance).  The most common risks are rash and diarrhea.  Other risks include changes in pituitary, thyroid, and adrenal function.  Rare auto-immune reactions (some severe and potentially life-threatening) have occurred.

CORT enrolled the first US patient to the prostate cancer study in 6/09. 

To learn more about this study, or to schedule consultation regard this and other treatments for prostate cancer, call 972-566-5588.   Additional information, including directions to the office are located at www.CORTPA.com.

Adjuvant Therapy of Melanoma: BMS CA184-029/EORTC 18071 Study at CORT

Melanoma, malignant cancer of the pigmented cells (melanocytes), has increased in incidence.  This cancer is the most serious form of skin cancer, with a higher likelihood of recurrence or metastatic spread than other forms of skin cancer.  Other less common sites for origination of melanoma include the pigmented layer of the retina, or mucosal areas such as the rectum.  Principle treatment is surgical, with wide excision.  The extent of local disease is defined by the T stage (tumor depth of invasion), and the N stage (presence of nodal involvement).  TNM staging for melanoma may be found at http://en.wikipedia.org/wiki/Melanoma.  Nodal staging is important in defining overall stage, so resection of lymph nodes to determine involvement has become a standard practice, in patients other than the shallowest depths of invasion (with more significant chances of nodal involvement).  The risk of lymph node sampling may include lymphedema, so sampling of nodes by selective means (sentinel lymph node dissection) is often employed first, with full regional lymphadenectomy reserved for cases with initially positive sentinel lymph nodes.  Patients with positive lymph nodes and no other evidence of metastatic disease spread are Stage III in overall stage.  The 5-year survival for Stage III disease ranges from 25-60%, depending on the extent of involvement. 

Efforts to improve the outcome of Stage III melanoma patients have focused on immunotherapy, because adjuvant radiation or chemotherapy have not improved outcome.  High dose Interferon-alpha-2b (Intron-A) has been studied in large, randomized placebo-controlled adjuvant Phase III studies (ECOG 1684, ECOG 1690).  Lower doses have also been studied in other randomized clinical trials.  An overview of the results of those randomized studies has been published (http://jco.ascopubs.org/cgi/content/full/20/7/1818).  The ECOG studies reported improvement in disease free survival (DFS), and the ECOG 1684 study reported an overall survival (OS) improvement that was not confirmed in other studies.  Interferon therapy has potentially serious toxicities, including abnormal liver functions, rash, fatigue, anemia, thrombocytopenia, leukopenia, abnormal thyroid function, and exacerbation of autoimmune phenomena.  Many patients are unable to complete interferon therapy at high dose, and the value of low dose therapy is not as certain.  In the ECOG interferon protocol, continuation of lower dose interferon continues for up to one year, and many patients are unable to complete the duration of therapy.  Studies utlizing a newer form of interferon (pegylated interferon alpha, the EORTC Trial 18991) have been reported more recently (ASCO 2007 Annual Meeting, Abstract 8504).  That study demonstrated reduced relapse, but again, survival was not improved.  Overall, the conclusion can be reached that Stage III melanoma patients should be offered interferon therapy, or a clinical trial of new treatment. 

Ipilimumab (MDX-010, Anti-CTLA4) is an antibody therapy that activate the immune response against melanoma.  Ipilimumab has been studied in patients with metastatic melanoma, and responses have been seen in 13% of patients treated, some of which were fairly durable.  The response rate appears to be somewhat higher than that of interferon in metastatic patients. 

Therefore, ipilimumab has entered testing for adjuvant therapy of Stage III melanoma.  This study is the BMS CA184-029/EORTC 18071 study http://clinicaltrials.gov/ct2/show/NCT00636168.  Patients with completely resected melanoma, with adequate lymph node dissection staging, good performance status, and absence of autoimmune disease are potential candidates.  Patients may not have received other adjuvant therapy for disease, and they must enter the study and be randomized within 12 weeks of surgery.  Other inclusion and exclusion criteria do apply.  The study is placebo controlled.  CORT has been selected as a participating site in this trial.  For more information on the study, visit the CORT website (www.CORTPA.com), or contact a Research Coordinator at 972-566-5588.  

CORT Clinical Trials Brochure: PDF Version

CORT offers a broad array of oncology clinical phase II-III studies for solid tumors and lymphomas.  The attached PDF lists our current or pending studies. For more information about our studies, visit the CORT website at www.CORTPA.com, or contact a Reseach Coordinator at 972-566-5588. 

CORT Clinical Trials December 2008

CORT Clinical Trials January 2009

CORT Clinical Trials February 2009

CORT Clinical Trials September 2009

CORT Symposium on Treatment of Her-2+ Breast Cancer

The Center for Oncology Research & Treatment will be hosting a symposium titled “Treatment of Her-2+ Breast Cancer” which will feature presentations by a team surgical, medical, and radiation oncologists at Medical City Dallas Hospital on Wednesday, October 28, 2009, from 6:30-8:30 PM. Perspectives on management issues from early to advanced stage disease, and integration of new therapies into practice will be highlighted in the conference. Here is the conference notice:

Breast Cancer Symposium

Treatment of Her-2 Positive Breast Cancer

With
Barry Mirtsching M.D.
Medical Oncology
Conference Chair
Director
Center for Oncology Research & Treatment
Dallas, TX

Peter Beitch M.D.
Surgical Oncology
ACoSOG Principle Investigator
Dallas Surgical Group

Timothy Nichols M.D.
Radiation Oncology
Breast Radiation Director
Northpoint Cancer Center

Located at Medical City Dallas, City Hall in Bld. E
7777 Forest Lane, Dallas TX 75230

Wednesday, Oct 28th 6:30 pm

Please call to RSVP:
972-566-5588

CORT Raising Funds for Susan Komen in Race-for-the-Cure

Dear Friends,

CORT has recently accepted the challenge to raise funds to support the 2009 Komen Dallas Race for the Cure®  on October 17th. 

Please join us in the fight by donating in support of my participation in the Race.  Your tax-deductible contribution will fund local outreach and awareness programs for underserved communities in the Dallas County area and national breast cancer research.

Donating is quick and easy.  Click here to visit my personal page and pledge your support.  If you would prefer you can mail a check or money order to my attention to the address below.  No donation is too small.  I truly appreciate your support.

Sincerely,

Barry Mirtsching
7777 Forest Land B242

Dallas, TX 75230-2525
 

To sponsor my participation online, click here.

Proleukin (Interleukin-2) Therapy for Renal Cell Carcinoma: Treatment Option for Select Patients

Therapy options for patients with metastatic renal cell carcinoma has expanded significantly, with the FDA approval of sunitinib (Sutent), sorafenib (Nexavar), everolimus (Affinitor), temsirolimus (Torisel), and bevacizumab (Avastin).  These drugs have significant anti-tumor and anti-angiogenic effects.  Progression-free survival (PFS) is improved when compared to placebo or alpha-interferon (Intron-A) therapy.  Many patients will respond to more than one of these agents, and therefore overall outcomes for patients receiving sequential treatments may be improved.   These therapies have expected and manageable toxicities and risks, and are delivered on an outpatient basis.  Nonetheless, these new therapies do not offer curative potential to any patient when used in patients with established metastatic disease.   Patients with reduced overall health and function (performance status) can be treated with these agents.

Interleukin-2 (IL-2, Proleukin) is an FDA approved therapy for metastatic renal cancer.   It is a potent immune stimulator, and it may have anti-angiogenic activity.  Since its clinical development nearly two decades ago, it remains the only therapy with a known curative potential for patients with metastatic renal carcinoma.  Treatment with IL-2 has substantial toxicity, priniciply secondary to capillary leak syndrome and vasodilation, which can result in serious hypotension, fluid accumulation, edema, pulmonary congestion, renal dysfunction, or other organ failure.  Patient selection for this form of therapy is critical.  Only patients with good performance status and adequate kidney, heart, and lung function are potential candidates for IL-2 treatment.  Treatment is delivered on an inpatient basis, under carefully-monitored circumstances, usually in the intensive care unit.  Treatment is delivered by a specialized team of oncologists and nurses, who are familiar with the specific program of IL-2 therapy, and have experience in management and prevention of toxicities.   A critical care physician (ICU physician) is also engaged in management.  Therapy lasts for 5 days, with several additional days potentially required for resolution of treatment-related lab or clinical changes.  Most of the treatment-related side effects abate rapidly after the therapy is completed.  A second cycle of inpatient IL-2 therapy is given after the patient has had a brief period of outpatient recovery.   In studies of IL-2 in metastatic kidney cancer, the overall response rate (out of 255 patients) = 15% (7% complete, 8% partial). That is not higher than other recently-approved medications.  However, the median duration of complete response (CR*) is 6.7+ years (range 7 months – 10+ years).  Those long-term results are not achieved by other treatments for metastatic renal cancer.

Additional information about IL-2 therapy is available at www.Proleukin.com.  CORT is a provider for IL-2 therapy in the North Texas area.  Our patients are treated in Medical City Dallas Hospital.

For information about CORT, or to schedule a consultation about treatment of renal cancer, call 972-566-5588 to speak with a Patient Care Coordinator.  Additional information about CORT and directions are available at www.CORTPA.com.

Patients Who Seek Information From Media Sources More Likely to Receive Newer Therapies

A study published in the April 1 issue of Cancer shows that colorectal cancer patients who seek out information about their therapy from media sources (internet, TV, etc.) are more likely to receive new therapies that those who do not.  The study was conducted by the Dana Farber Cancer Institute, with lead investigator Dr. Stacey Gray.  The study collected information from 633 patients in the Pennsylvania Cancer Registry.  Those patients who sought information were 2.8 times more likely to have heard about newer treatments for their disease, and they were 3.2 times more likely to receive those therapies.  While the study does not examine outcomes of those patients, outcomes of patients who have received newer treatments for colon cancer are likely to be superior to those who have not. 

This study finding is somewhat intuitive.  At the CORT research center, we have observed the influence of patient education on treatment selection for quite some time.  Patients who have sought out more information about their therapy have come for consultation have in many instances been offered new cancer therapy agents or trial participation options that were not initially suggested in their initial consultatons.   The evidence that new agents (cetuximab, bevacizumab, panitumumab) have improved the outcomes of survival in colon cancer is now unequivocal.   Information-seeking patients will continue to be more apt to receive the next generation of new agents. 

CORT is currently investigating the use of genetic and molecular markers to select patients for adjuvant therapy of Stage II colon cancer (ECOG 5202 Study), the use of cetuximab (Erbitux) in combination with FOLFOX therapy in Stage III colon cancer patients with wild-type k-ras mutation status (N0147 Study), and the comparison of the relative benefit of bevacizumab (Avastin) versus panitumumab (Vectibix) in combination with FOLFOX therapy as first-line treatment of metastatic colon cancer patients with wild-type k-ras mutations status.  The thrust of the investigations at CORT is to seek more information that will allow treatments to be more individualized to the patient disease characteristics, since colon cancers are not all the same, even though they may have similar appearances when analyzed by conventional methods. 

For more information about colon cancer therapy, visit out website at www.CORTPA.com.  For  requests for consultation, contact CORT at 972-566-5588 (Dallas) or 972-981-4012 (Plano).

FDA Approves Use of Imatinib (Gleevec) for Adjuvant Therapy of Resected GIST

On December 19, 2008, the FDA approved use of imatinib (Gleevec) for adjuvant therapy of resected adult GIST (GI Stromal Tumor). 

GISTs are tumors of the bowel wall that originate in the interstitial cells of Cajal, part of the autonomic cell network that control movement of food and fluids through the bowel.  GIST occurs in 5000-6000 patients per year in the US.  The tumors have an appearance often confused with other bowel wall smooth muscle tumors, known as leiomyomas or sarcomas.  GISTs have mutations of cell surface proteins that activate cell proliferation, primarily in the cellular gene c-kit, but also in PDGFRA (platelet derived growth factor receptor-A).  Common mutations are in exon 11 and exon 9 of the c-kit gene.  Imatinib was found to inhibit the activation of c-kit in patients (those with imatinib-sensitive mutations), and it was approved in 2001 by the FDA for treatment of metastatic GIST, after clinically-meaningful responses (overall approximately 40% of patients have radiographic responses by CT scan, compared to historical responses seen in only 0-5% of chemotherapy-treated GIST)  and disease control was demonstrated in early studies.  Further investigation has shown that imatinib improves progression-free survival (PFS).  The PFS has ranged between 17-24 months in metastatic GIST, depending on the dose of imatinib.  Significant differences in response and PFS with imatinib therapy have been established for differing mutations in c-kit (and PDGFRA). 

The use of imatinib for adjuvant therapy (post-resection treatment) after complete resection of GIST tumors (when patients have no other apparent disease) was studied in the ACSOG Z9001 study.  This was a randomized, double-blind study of imatinib for patients with GIST at high risk for recurrence after resection.  The study enrolled 644 patients, and it was stopped in 2007, after a significant improvement in PFS was determined for patients receiving adjuvant imatinib therapy (400 mg/d x 12 months).  After 18 months of median follow-up, PFS was 97% in the imatinib group versus 83% in the placebo group.  The improvement in PFS was seen across a broad range of tumor size. 

Therefore, patients who have had surgery for GIST should now receive at least one year of adjuvant imatinib therapy.  The duration of imatinib therapy continues to be studied in other ongoing investigations.   It is very important for patients with GIST tumors to be correctly identified when resection occurs, so the benefit of adjuvant therapy is not potentially missed.  The CD117 stain may help to differentiate GIST from other soft tissue tumors of the bowel.  However, there have been reports of CD117-negative GISTs.  PDGFRA staining may also prove helpful.  Molecular genetic analysis of c-kit and PDGFRA may not only help to  identify patients with GIST, but because certain mutations in these genes is associated with imatinib resistance, testing may serve to help assess the potential benefit of therapy, as other drugs have been developed that have activity in imatinib-resistant forms of GIST.  These specialized tests may be obtained by consultation and specimen referral to specialized pathology labs.  Such testing can be done on archival tumor tissue.   For example, tumor tissue may be sent for analysis at MD Anderson Pathology Lab.  A requistion form and instruction is here in the attachment:

MD Anderson Pathology Requisition

Other labs that have experience in testing GISTs:

• ARUP Laboratory, Salt Lake City (http://www.aruplab.com/)
• MD Anderson Cancer Center, Houston, TX (http://www.mdanderson.org/labs/mdl/)
• Oregon Health & Science University, Portland, OR (http://www.heinrich-corless.net/services.html)

A review of expanding information about GIST therapy is beyond the scope of this brief post.  Additional information is available through GIST support groups (www.liferaftgroup.org, www.gistsupport.org, www.gistinfo.org). Patients who are interesting on medical oncology consultation at CORT may call 972-566-5588.  Information about CORT is available at our website: www.CORTPA.com.