Experimental Drug Benefits Patients with Advanced Prostate Cancer
The experimental drug cabazitaxel has improved the survival of some patients with advanced prostate cancer compared with those who received standard chemotherapy, according to results from a randomized phase III clinical trial presented last week at the Genitourinary Cancers Symposium in San Francisco. Although the benefit was modest (several months), there currently are no effective treatments for patients with this form of the disease, called metastatic castration-resistant, or hormone-refractory, prostate cancer.
“This is the first positive study of its kind,” said Dr. Nicholas Vogelzang, chair and medical director of the Developmental Therapeutics Committee of the company US Oncology, who moderated a press briefing on March 3 ahead of the symposium. Cabazitaxel should clearly be considered now as an alternative for men in whom standard chemotherapy has failed, he added.
The international TROPIC (Treatment of Hormone-Refractory Metastatic Prostate Cancer Previously Treated with a Taxotere-Containing Regimen) study included 755 men whose prostate cancers had progressed despite treatment with hormone therapy and subsequent chemotherapy with docetaxel, which is the standard drug used to treat men with advanced disease. The participants were randomly assigned to receive cabazitaxel plus prednisone or another chemotherapy drug, mitoxantrone, also in combination with prednisone.
With a median follow-up of 12.8 months, median overall survival for men in the cabazitaxel group was 15.1 months compared with 12.7 months for patients in the mitoxantrone group. This translates into about a 30 percent reduction in the risk of death, said lead investigator Dr. Oliver Sartor of the Tulane Cancer Center.
Cabazitaxel—which, like docetaxel, is part of a class of drugs known as taxanes—was designed to be active in cells that develop resistance to docetaxel, which happens in many patients with this disease. The drug appears to elude a mechanism in prostate cancer cells that pumps anticancer drugs out of the cells before they have a chance to be effective, the researchers said.
The improvement in overall survival was consistent across different patient subgroups, such as those stratified by age, race, and certain co-morbidities, Dr. Sartor said. And men treated with cabazitaxel also had improvements in important measures such as length of survival without tumor growth (progression-free survival) and significant tumor shrinkage following treatment (response rate).
In terms of side effects, patients who received cabazitaxel were more likely to experience febrile neutropenia, a high fever associated with significant reductions in white blood cells called neutrophils. So, Dr. Sartor advised, patients treated with cabazitaxel need to be “carefully watched” for this toxicity.
Because there is no well-accepted standard treatment for men whose tumors no longer respond to docetaxel, choosing the treatment with which cabazitaxel would be compared was difficult, Dr. Sartor noted. Mitoxantrone was chosen instead of a placebo because it has some activity in these types of patients, he explained.
“It’s a promising feature that you can treat patients with a taxane-based chemotherapy in a second-line setting and still have a response and reasonable tolerance,” said Dr. Daniel George, an assistant professor of medicine and urologic surgery at the Duke University Comprehensive Cancer Center. And patients who respond well to first-line treatment with docetaxel tend to fare better with second- and third-line therapies, Dr. George added. “So, for those patients this may be even more of an advance.”
The results also further confirm that in patients with advanced prostate cancer, chemotherapy isn’t strictly a last ditch treatment, Dr. George said, but that it “can really extend survival even further than we originally recognized.”
Noting that advances in treating cancer have always been incremental, Dr. Vogelzang said that the results were similar to those from the 2004 study that demonstrated the benefit of docetaxel as treatment for advanced prostate cancer.
Sanofi-Aventis, which manufactures cabazitaxel, is expected to seek FDA approval of the experimental drug as a second-line treatment. It would be the first FDA-approved agent for this indication.
The third annual symposium was co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
—Edward R. Winstead and Carmen Phillips
Tuesday, March 9, 2010
Urologists vs Oncologists on Treating PCa
Researchers used Medicare data to track the specialty and primary care visits of some 85,000 men with localized prostate cancer. Half the patients were seen exclusively by urologists, and 44% by urologists and radiologists. Visits to primary care physicians in the interval between diagnosis and treatment were infrequent (22%).
The researchers found that men consulting only urologists were much more likely to undergo radical prostatectomy, while those consulting both a urologist and a radiation oncologist were more likely to receive radiation therapy.
A commentator, looking at what he calls the "prostate cancer treatment bazaar," finds "an embarrassing lack of comparative clinical trials" among the therapies. In order to offer more "than just a marketing pitch" to patients trying to choose, he recommends that primary care physicians participate in shared decision making.
Archives of Internal Medicine article (Free)
Archives of Internal Medicine commentary (Subscription required)
The researchers found that men consulting only urologists were much more likely to undergo radical prostatectomy, while those consulting both a urologist and a radiation oncologist were more likely to receive radiation therapy.
A commentator, looking at what he calls the "prostate cancer treatment bazaar," finds "an embarrassing lack of comparative clinical trials" among the therapies. In order to offer more "than just a marketing pitch" to patients trying to choose, he recommends that primary care physicians participate in shared decision making.
Archives of Internal Medicine article (Free)
Archives of Internal Medicine commentary (Subscription required)
Saturday, March 6, 2010
Labcorp View on Prostate Cancer Diagnosis
Overview
Prostate cancer accounts for approximately one-fourth of newly diagnosed cancers and almost
10% of cancer-related deaths in men in the United States.1 Traditional screening for prostate
cancer using the prostate-specific antigen (PSA) test has not only increased the number of
cases identified annually but has also increased the proportion of patients who present with
early-stage disease. While PSA is a commonly used screening marker, the diagnosis of prostate
cancer also depends upon the findings from prostate tissue biopsies. Biopsy findings, including
tumor grade and the extent of the cancer (Gleason score), help determine patient prognosis and
influence treatment decisions. Although PSA testing has been helpful in identifying prostate
cancer, there is an ongoing concern called the “prostate dilemma,” because a growing number
of patients present with elevated PSA but with no evidence of disease on biopsy. This issue has
prompted even greater focus on new guidelines, testing, and treatment for prostate cancer.
In March 2009, The American Urological Association (AUA) issued an updated prostate-specific
antigen statement. AUA sites 2 key differences from the policy it issued in 20002:
1. The age for obtaining a baseline PSA has been lowered to 40 years.
2. The current policy no longer recommends a single, threshold value of PSA that should prompt
prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily
on PSA and digital rectal exam (DRE) results but should take into account multiple factors,
including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity,
prior biopsy history, and co-morbidities.
These revised guidelines will assist physicians in managing a potential prostate cancer diagnosis.
In addition, Laboratory Corporation of America® Holdings (LabCorp) offers an array of tests to
assist physicians with the diagnosis, prognosis, and management of prostate cancer. These tests
include CaPDETECT: PCA3™, GST-P1, and circulating tumor cells
Prostate cancer accounts for approximately one-fourth of newly diagnosed cancers and almost
10% of cancer-related deaths in men in the United States.1 Traditional screening for prostate
cancer using the prostate-specific antigen (PSA) test has not only increased the number of
cases identified annually but has also increased the proportion of patients who present with
early-stage disease. While PSA is a commonly used screening marker, the diagnosis of prostate
cancer also depends upon the findings from prostate tissue biopsies. Biopsy findings, including
tumor grade and the extent of the cancer (Gleason score), help determine patient prognosis and
influence treatment decisions. Although PSA testing has been helpful in identifying prostate
cancer, there is an ongoing concern called the “prostate dilemma,” because a growing number
of patients present with elevated PSA but with no evidence of disease on biopsy. This issue has
prompted even greater focus on new guidelines, testing, and treatment for prostate cancer.
In March 2009, The American Urological Association (AUA) issued an updated prostate-specific
antigen statement. AUA sites 2 key differences from the policy it issued in 20002:
1. The age for obtaining a baseline PSA has been lowered to 40 years.
2. The current policy no longer recommends a single, threshold value of PSA that should prompt
prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily
on PSA and digital rectal exam (DRE) results but should take into account multiple factors,
including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity,
prior biopsy history, and co-morbidities.
These revised guidelines will assist physicians in managing a potential prostate cancer diagnosis.
In addition, Laboratory Corporation of America® Holdings (LabCorp) offers an array of tests to
assist physicians with the diagnosis, prognosis, and management of prostate cancer. These tests
include CaPDETECT: PCA3™, GST-P1, and circulating tumor cells
Friday, March 5, 2010
MDV3100 in Clinical Development for Advanced PCa
MDV3100 is an investigational therapy in clinical development for the treatment of advanced prostate cancer.
Overview
MDV3100 is the first triple-acting, oral anti-androgen in development for the treatment of advanced prostate cancer. The treatment of advanced prostate cancer represents a critical unmet medical need, as patients with this stage of the disease have few treatment options and a poor prognosis.
MDV3100 has a novel mechanism of action that is unlike that of the leading anti-androgen (hormonal) therapy bicalutamide. The first triple-acting, oral anti-androgen, MDV3100 has been shown in preclinical studies to provide a more complete suppression of the androgen receptor pathway than bicalutamide. MDV3100 slows growth and induces cell death in bicalutamide-resistant cancers via three complementary actions – MDV3100 blocks testosterone binding to the androgen receptor, impedes movement of the androgen receptor to the nucleus of prostate cancer cells (nuclear translocation), and inhibits binding to DNA. Preclinical data published in Science in April 2009 demonstrated that MDV3100 is superior to bicalutamide in each of these three actions. Click here for Science article.
Medivation is evaluating MDV3100 in collaboration with Astellas, in an ongoing, open-label, U.S., Phase 1-2 study. The interim results showed that MDV3100 was associated with anti-tumor activity in patients who had become resistant to bicalutamide or other standard anti-androgen treatments, including both patients who had failed prior chemotherapy and patients who were chemotherapy naïve. Anti-tumor activity was demonstrated by reductions in prostate-specific antigen levels, improvement or stabilization in tumors that had spread to soft tissue or bone, and a decrease in circulating tumor cells, which has been associated in published literature with improved survival in patients with castration-resistant prostate cancer.
The Phase 3 AFFIRM trial is currently enrolling men with castration-resistant prostate cancer who were previously treated with docetaxel-based chemotherapy. Click here for clinical trial information.
Overview
MDV3100 is the first triple-acting, oral anti-androgen in development for the treatment of advanced prostate cancer. The treatment of advanced prostate cancer represents a critical unmet medical need, as patients with this stage of the disease have few treatment options and a poor prognosis.
MDV3100 has a novel mechanism of action that is unlike that of the leading anti-androgen (hormonal) therapy bicalutamide. The first triple-acting, oral anti-androgen, MDV3100 has been shown in preclinical studies to provide a more complete suppression of the androgen receptor pathway than bicalutamide. MDV3100 slows growth and induces cell death in bicalutamide-resistant cancers via three complementary actions – MDV3100 blocks testosterone binding to the androgen receptor, impedes movement of the androgen receptor to the nucleus of prostate cancer cells (nuclear translocation), and inhibits binding to DNA. Preclinical data published in Science in April 2009 demonstrated that MDV3100 is superior to bicalutamide in each of these three actions. Click here for Science article.
Medivation is evaluating MDV3100 in collaboration with Astellas, in an ongoing, open-label, U.S., Phase 1-2 study. The interim results showed that MDV3100 was associated with anti-tumor activity in patients who had become resistant to bicalutamide or other standard anti-androgen treatments, including both patients who had failed prior chemotherapy and patients who were chemotherapy naïve. Anti-tumor activity was demonstrated by reductions in prostate-specific antigen levels, improvement or stabilization in tumors that had spread to soft tissue or bone, and a decrease in circulating tumor cells, which has been associated in published literature with improved survival in patients with castration-resistant prostate cancer.
The Phase 3 AFFIRM trial is currently enrolling men with castration-resistant prostate cancer who were previously treated with docetaxel-based chemotherapy. Click here for clinical trial information.
Proto9n Beam Radiation Oncology Update
Proton Therapy Achieves Good Long-Term Local Control of Sinonasal Cancer
Elsevier Global Medical News. 2010 Mar 3, S London
CHANDLER, Ariz. (EGMN) - Proton beam therapy yields a high 87% rate of local control at 5 years in patients with locally advanced cancer of the sinuses or nasal cavity, according to a retrospective analysis of 99 patients who were treated with this emerging technology.
The results highlight the need for multicenter prospective studies to better define how this therapy fits into the management of sinonasal cancer, presenting author Dr. Annie W. Chan said at a head and neck cancer symposium sponsored by the American Society for Radiation Oncology.
"Even with 3-D-conformal radiation therapy [3DCRT] or intensity-modulated radiation therapy [IMRT], the local control rate [of sinonasal cancer] has not been very impressive," said Dr. Chan, a radiation oncologist at Massachusetts General Hospital in Boston. "There is a lot of room for improvement in just local control."
Protons are as effective as the photons of conventional radiation therapy in tissue, she observed. But protons have some distinct physical properties - such as a lower dose where the beam first enters tissue and a rapid dose falloff as it exits the target - that offer advantages.
Dr. Chan and her coinvestigators retrospectively analyzed outcomes among 99 patients who underwent proton beam therapy at Massachusetts General Hospital between 1991 and 2003 for newly diagnosed sinonasal cancer.
The patients had a median age of 51 years, and the sex distribution was nearly equal. Two-thirds had stage T4b disease. The most common tumor types were sinonasal undifferentiated carcinoma (SNUC) or squamous cell carcinoma (34%) and neuroendocrine tumors or esthesioneuroblastomas (28%).
A third of the patients had a biopsy alone, whereas the rest had a partial or gross total resection. In all, 27% of patients received chemotherapy.
The total radiation dose was 70 GyE, of which protons made up 57%. Patients received combined proton and photon therapy because the hospital did not have a dedicated proton machine at the time, Dr. Chan explained. "For the sinus area and upper neck, we used protons alone. For the lower neck, we used photons only," she said.
With a median duration of follow-up of 5.3 years among all patients and 8.5 years among living patients, the estimated 5-year rates of local and regional control were 87% and 89%, respectively, according to Dr. Chan, who reported receiving study funding from a government grant.
The rate of local control did not differ significantly by tumor type, extent of surgery (resection vs. biopsy only), type of surgical approach (transfacial or craniofacial vs. endoscopic surgery or craniotomy alone), or T stage (T3b vs. T4a vs. T4b).
In a multivariate analysis, patients had a higher risk of death if they had a Karnofksy performance status score of 90% or lower at the time of radiation vs. a higher score (hazard ratio 3.1, P = .003); SNUC or squamous cell carcinoma vs. other tumor types (HR 2.4, P = .002); or a T4b stage vs. a T3 or T4a stage (HR 3.6, P less than .001). In contrast, the extent of surgery and the surgical approach did not significantly influence this outcome.
The first site of failure was most commonly a distant site (seen in 26% of patients), followed by a local site (11%) and a regional site (8%).
Patients had an increased risk of distant metastases if they had a primary tumor located in the sphenoid or ethmoid sinuses vs. maxillary sinuses or nasal cavity (P = .007) or a T4b stage (P = .002). "Maybe T4b stage is a group of patients in which we should consider induction chemo rather than giving induction chemo to all patients with sinonasal cancer," Dr. Chan commented.
The leading grade 3 or higher late toxicity was soft tissue toxicity (mainly sinocutaneous fistulas occurring along transfacial scars), seen in 9% of patients at 5 years, Dr. Chan said. The other toxicities of this severity were visual or ocular (7%), bone (6%), and neurologic (3%).
Patients were more likely to develop a grade 4 sinocutaneous fistula if they had a surgery by the transfacial or craniofacial surgical approach (P = .03). No one who was treated with an endoscopic approach or craniotomy alone experienced this complication.
In addition, patients were more likely to develop grade 2 or higher neurologic toxicity if their duration of radiation therapy was 40 days or less (P = .002) or if they had adenoid cystic carcinoma vs. other tumor types (P = .002). "For the adenoid cystic carcinoma, we usually cover the perineural spread in our clinical target volume, which could increase the risk of neurologic toxicity," she commented.
A comparison of the 5-year local control rates achieved with proton therapy in the study and with 3DCRT or IMRT in historical series favored the former (87% vs. 21%-63%). "However, all of these studies are single-institution retrospective studies," Dr. Chan cautioned. "Definitive conclusions therefore cannot be made."
Rates of grade 3 or higher late complications with proton therapy were comparable to those with the other two types of radiation therapy.
"Proton beam results in very encouraging outcomes in patients with locally advanced sinonasal cancer," Dr. Chan concluded. "Multi-institutional prospective studies, particularly in comparison with IMRT, are necessary to define the role of protons in the treatment of this rare and aggressive malignancy."
Commenting on the study in a related press briefing, Dr. Louis B. Harrison, chair of radiation oncology at the Beth Israel Medical Center in New York, said that the cost of proton therapy "is something that we all grapple with."
The incremental benefit of this therapy is something that the field is striving to learn, according to Dr. Harrison, who reported having no conflicts of interest. But "you can't learn unless there are enough centers doing it, so that you can accumulate the data. So this is really something that requires a lot of attention in our current-day health care debate."
Dr. Chan disclosed no conflicts of interest.
--------------------------------------------------------------------------------
click for full
Elsevier Global Medical News. 2010 Mar 3, S London
CHANDLER, Ariz. (EGMN) - Proton beam therapy yields a high 87% rate of local control at 5 years in patients with locally advanced cancer of the sinuses or nasal cavity, according to a retrospective analysis of 99 patients who were treated with this emerging technology.
The results highlight the need for multicenter prospective studies to better define how this therapy fits into the management of sinonasal cancer, presenting author Dr. Annie W. Chan said at a head and neck cancer symposium sponsored by the American Society for Radiation Oncology.
"Even with 3-D-conformal radiation therapy [3DCRT] or intensity-modulated radiation therapy [IMRT], the local control rate [of sinonasal cancer] has not been very impressive," said Dr. Chan, a radiation oncologist at Massachusetts General Hospital in Boston. "There is a lot of room for improvement in just local control."
Protons are as effective as the photons of conventional radiation therapy in tissue, she observed. But protons have some distinct physical properties - such as a lower dose where the beam first enters tissue and a rapid dose falloff as it exits the target - that offer advantages.
Dr. Chan and her coinvestigators retrospectively analyzed outcomes among 99 patients who underwent proton beam therapy at Massachusetts General Hospital between 1991 and 2003 for newly diagnosed sinonasal cancer.
The patients had a median age of 51 years, and the sex distribution was nearly equal. Two-thirds had stage T4b disease. The most common tumor types were sinonasal undifferentiated carcinoma (SNUC) or squamous cell carcinoma (34%) and neuroendocrine tumors or esthesioneuroblastomas (28%).
A third of the patients had a biopsy alone, whereas the rest had a partial or gross total resection. In all, 27% of patients received chemotherapy.
The total radiation dose was 70 GyE, of which protons made up 57%. Patients received combined proton and photon therapy because the hospital did not have a dedicated proton machine at the time, Dr. Chan explained. "For the sinus area and upper neck, we used protons alone. For the lower neck, we used photons only," she said.
With a median duration of follow-up of 5.3 years among all patients and 8.5 years among living patients, the estimated 5-year rates of local and regional control were 87% and 89%, respectively, according to Dr. Chan, who reported receiving study funding from a government grant.
The rate of local control did not differ significantly by tumor type, extent of surgery (resection vs. biopsy only), type of surgical approach (transfacial or craniofacial vs. endoscopic surgery or craniotomy alone), or T stage (T3b vs. T4a vs. T4b).
In a multivariate analysis, patients had a higher risk of death if they had a Karnofksy performance status score of 90% or lower at the time of radiation vs. a higher score (hazard ratio 3.1, P = .003); SNUC or squamous cell carcinoma vs. other tumor types (HR 2.4, P = .002); or a T4b stage vs. a T3 or T4a stage (HR 3.6, P less than .001). In contrast, the extent of surgery and the surgical approach did not significantly influence this outcome.
The first site of failure was most commonly a distant site (seen in 26% of patients), followed by a local site (11%) and a regional site (8%).
Patients had an increased risk of distant metastases if they had a primary tumor located in the sphenoid or ethmoid sinuses vs. maxillary sinuses or nasal cavity (P = .007) or a T4b stage (P = .002). "Maybe T4b stage is a group of patients in which we should consider induction chemo rather than giving induction chemo to all patients with sinonasal cancer," Dr. Chan commented.
The leading grade 3 or higher late toxicity was soft tissue toxicity (mainly sinocutaneous fistulas occurring along transfacial scars), seen in 9% of patients at 5 years, Dr. Chan said. The other toxicities of this severity were visual or ocular (7%), bone (6%), and neurologic (3%).
Patients were more likely to develop a grade 4 sinocutaneous fistula if they had a surgery by the transfacial or craniofacial surgical approach (P = .03). No one who was treated with an endoscopic approach or craniotomy alone experienced this complication.
In addition, patients were more likely to develop grade 2 or higher neurologic toxicity if their duration of radiation therapy was 40 days or less (P = .002) or if they had adenoid cystic carcinoma vs. other tumor types (P = .002). "For the adenoid cystic carcinoma, we usually cover the perineural spread in our clinical target volume, which could increase the risk of neurologic toxicity," she commented.
A comparison of the 5-year local control rates achieved with proton therapy in the study and with 3DCRT or IMRT in historical series favored the former (87% vs. 21%-63%). "However, all of these studies are single-institution retrospective studies," Dr. Chan cautioned. "Definitive conclusions therefore cannot be made."
Rates of grade 3 or higher late complications with proton therapy were comparable to those with the other two types of radiation therapy.
"Proton beam results in very encouraging outcomes in patients with locally advanced sinonasal cancer," Dr. Chan concluded. "Multi-institutional prospective studies, particularly in comparison with IMRT, are necessary to define the role of protons in the treatment of this rare and aggressive malignancy."
Commenting on the study in a related press briefing, Dr. Louis B. Harrison, chair of radiation oncology at the Beth Israel Medical Center in New York, said that the cost of proton therapy "is something that we all grapple with."
The incremental benefit of this therapy is something that the field is striving to learn, according to Dr. Harrison, who reported having no conflicts of interest. But "you can't learn unless there are enough centers doing it, so that you can accumulate the data. So this is really something that requires a lot of attention in our current-day health care debate."
Dr. Chan disclosed no conflicts of interest.
--------------------------------------------------------------------------------
click for full