CONTACT:
Michael Blash, Zeneca Pharmaceuticals, 302-886-5465, [email protected]
Elizabeth Miller, InterScience, 202-973-0374, [email protected]
Bob Schwadron, InterScience, 212-468-3616, [email protected]
FOR IMMEDIATE RELEASE
TWO PROSTATE CANCER MEDICATIONS MAY HELP PATIENTS WHEN USED EARLIER OR IN COMBINATION WITH RADIATION TREATMENTS
New Findings with ZOLADEX and CASODEX Presented at AUA
SAN DIEGO--June 1, 1998--Both the LHRH-A agent ZOLADEX(R) (goserelin acetate implant) and the antiandrogen CASODEX(R) (bicalutamide) Tablets may have a role in treating prostate cancer in patients diagnosed with early stage disease, according to data released here today at the 93rd Annual Meeting of the American Urological Association (AUA). One study presented at AUA (Abstract #496) shows that ZOLADEX may offer disease control and survival benefits when combined with radiation in initial therapy for prostate cancer in high risk patients, while two other trials (Abstracts #1301 and #490) show that monotherapy with CASODEX 150 mg may improve certain quality-of-life parameters in patients with both advanced and early stage disease. A fourth study (Abstract #972) evaluating the effect of one type of hormonal prostate cancer therapy known as Combined Androgen Blockade (CAB) on biochemical progression of disease suggests that use of the prostate specific antigen (PSA) test may be an important tool to monitor the effect of combination therapy with CASODEX and ZOLADEX on local recurrence of prostate cancer, further spread of disease, and overall survival. The PSA test is an accepted and commonly used diagnostic tool used to detect the presence of prostate cancer. CAB therapy is an important milestone in the treatment of advanced prostate cancer. This therapeutic approach uses the combination of a luteinizing hormone-releasing hormone analogue (LHRH-A) such as ZOLADEX with an antiandrogen such as CASODEX to obtain maximum suppression of testosterone, the male hormone that can stimulate growth of cancerous cells in the prostate gland. Suppression of testosterone by LHRH-A is also referred to as medical cast! ration.
Adding ZOLADEX to Radiation Offers Improved Local Control and Survival
"Adjuvant Hormonal Therapy with Goserelin Improves Survival in Patients with Locally Advanced Prostate Cancer Treated with Radiotherapy" by Dr. Michel Bolla and colleagues at University Hospital in Grenoble, France [Abstract #496 based on data initially published in the New England Journal of Medicine on July 31, 1997 (N Engl J Med. 1997;337:295-300)], evaluated the benefit of immediately adding ZOLADEX to radiation therapy in 401 patients at high risk of metastatic prostate cancer.
The randomized study showed that adjuvant treatment with ZOLADEX, initiated simultaneously with radiotherapy and continued every four weeks for three years, may dramatically improve the five-year overall survival of patients with locally advanced prostate cancer. Specifically, adding therapy with ZOLADEX to radiation significantly increased (p<0.001) five-year local control from 77 percent to 97 percent and clinical disease-free survival from 36 percent to 74 percent, leading to a significant increase (p<0.001) in overall survival at five years from 62 percent to 79 percent.
"While there is still some uncertainty as to the optimal chronology for administering hormonal therapy," said Dr. Bolla, who presented the study at AUA, "the EORTC joint study suggests that ZOLADEX should be initiated at the very start of radiation therapy, and given for three years."
Two Studies Support Use of Monotherapy With CASODEX at Different Stages of Prostate Cancer
Already proven safe and effective for the treatment of advanced prostate cancer at a 50 mg dose when used in combination with an LHRH-A (medical castration), CASODEX is now under study for use as monotherapy at a daily 150 mg (single tablet) dose both in advanced prostate cancer and in earlier stages of the disease.
Important to the evaluation of CASODEX as monotherapy at any stage is its potential for preserving patient well-being, which was the subjects of two studies featured at this year's AUA meeting.
The first of these studies, "Prospects for Improving Survival in Early Prostate Cancer: Results and Ongoing Studies with the Non-Steroidal Anti-Androgen Bicalutamide (CASODEX)" by Dr. Peter Iversen, University of Copenhagen, Denmark, and associates (Abstract #1301), documented significant improvements in sexual interest and physical capacity, two important quality-of-life measurements, with CASODEX. The researchers combined data from two trials of CASODEX versus castration in a total of 1,453 patients with advanced prostate cancer. In patients with nonmetastatic disease, survival was similar in both the CASODEX and castration groups.
"Two published studies, the EORTC trial presented by Bolla et al (Abstract #496) and the study conducted by the Medical Research Council in the United Kingdom, have demonstrated improved survival following early endocrine therapy in patients with nonmetastatic prostate cancer, but questions remain about the effect of early endocrine therapy on quality of life," said Dr. Iversen, who presented the data at AUA. "Our data support additional clinical studies to evaluate the potential use of CASODEX in earlier stages of prostate cancer, either alone or as adjuvant therapy. As a consequence, three large trials have almost completed enrollment of the planned 7,500 patients with nonmetastatic prostate cancer to investigate the value of CASODEX in this early phase of the disease."
The second monotherapy study, "Bicalutamide Monotherapy Versus Flutamide Plus Goserelin in Prostate Cancer Patients: Preliminary Results of an Italian Prostate Cancer Group (PONCAP) Study" by Dr. Pasquale Ditonno of Bari, Italy and associates (Abstract #490), compared the efficacy of CASODEX as monotherapy to a CAB regimen using flutamide plus ZOLADEX.
A total of 220 patients with advanced prostate cancer (stages C and D) were randomized to receive either CASODEX (150 mg daily) or flutamide (750 mg daily) plus ZOLADEX (3.6 mg every four weeks). Median follow-up time was 24 months.
"While the percentage of deaths and disease progression events were similar for patients on either treatment, patients on monotherapy with CASODEX 150 mg experienced fewer side effects and were more likely to maintain normal erections," said Dr. Ditonno. "While preliminary, this data supports the safety and efficacy of monotherapy with CASODEX 150 mg for advanced prostate cancer and its ability to preserve sexual potency, which is an important quality of life consideration for many men."
No unexpected side effects were observed with either regimen studied. Diarrhea and hot flashes were more common in the CAB group, while gynecomastia (swollen, painful breasts) was more common in patients treated with CASODEX 150 mg alone. Importantly, three times as many patients in the CAB group stopped treatment because of drug side effects than those in the CASODEX 150 mg group (13.4 percent vs 4.6 percent, respectively).
Using PSA to Monitor the Biochemical Impact of CAB
While CAB has been proven an effective treatment for improving time to progression and survival, its effect on biochemical progression (specifically PSA levels), progression of distant disease, and recurrence of local disease have not previously been documented on a long-term basis.
With this in mind, the European Study Group on Neoadjuvant Treatment undertook a clinical trial, "Neoadjuvant Combined Androgen Deprivation Therapy in Locally Confined Prostatic Carcinoma: 3-4 Years of Follow Up of a European Randomized Study" (Abstract #972), to evaluate the short- and long-term biochemical effects of CAB before prostatectomy compared to prostatectomy alone, in 320 patients with localized prostate cancer.
"An analysis at three to four years of follow up indicates no significant difference in PSA progression between those treated with CAB versus radical prostatectomy," said Professor Claude Schulman, who presented the data at AUA. "Longer follow-up is needed to evaluate the ability of CAB to keep the disease under control both locally and in other parts of the body."
Background on Prostate Cancer, ZOLADEX and CASODEX
According to the American Cancer Society, more than 189,500 American men will be diagnosed with prostate cancer in 1998, with 39,200 deaths resulting from the disease. Prostate cancer is the most frequently diagnosed of all malignancies in men--other than certain skin cancers--and is second only to lung cancer as a cause of cancer-related deaths in men.
Developed, manufactured, and marketed by Zeneca Pharmaceuticals, ZOLADEX is an effective and well-tolerated initial therapy used for the palliative treatment of advanced prostate cancer. The drug is administered by subcutaneous injection and has been available since 1989 as a monthly implant (3.6 mg), and since 1996 as a three-month implant (10.8 mg). Both formulations have been shown to be as effective as orchiectomy (surgical castration) in controlling the spread of prostate cancer, thus offering men a choice between pharmacologic therapy and radical surgery. In treatment groups, adverse events with ZOLADEX were reported as mild to moderate. Hot flashes are the most frequently reported side effect with ZOLADEX, and unspecified cancer-related pain and lower urinary tract symptoms may also be common.
CASODEX, also from Zeneca Pharmaceuticals, was approved by the Food and Drug Administration in October 1995 for use in combination therapy with an LHRH-A such as ZOLADEX for treatment of advanced metastatic prostate cancer (stage D2). In 1997, CASODEX became the most widely prescribed antiandrogen in the United States (Source: IMS America prescription data). CASODEX 50 mg in combination with an LHRH-A is generally well-tolerated. The most commonly reported adverse events with CASODEX plus LHRH-A are hot flashes, pain, constipation, back pain, pelvic pain, nausea, diarrhea, and infection.
Zeneca Pharmaceuticals is a business unit of Zeneca Inc., based in Wilmington, Del. In the United States, Zeneca Inc. is a $3.4 billion bioscience business with approximately 7,500 employees. Zeneca Inc. is a wholly-owned subsidiary of the U.K.-based Zeneca Group PLC (NYSE:ZEN), a major $8.6 billion international bioscience business engaged in the research, development, manufacture, and marketing of ethical (prescription) pharmaceuticals, agricultural and specialty chemical products, and the supply of health care services.
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NOTE: For full prescribing information for CASODEX(r) (bicalutamide) Tablets and ZOLADEX(r) (goserelin acetate implant), please call 1-800-456-3669, ext. 2231, or access the World Wide Web at www.prostateinfo.com.
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