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Thalidomide Trials Data Suggest Benefits in Renal Cell Carcinoma, Prostate Cancer and Melanoma

WARREN, N.J., June 4 /PRNewswire-FirstCall/ -- Celgene Corporation (NASDAQ:CELG) -- Clinical investigators from leading cancer research centers around the world presented extensive clinical data on THALOMID(R) (thalidomide) in a broad range of hematological and solid tumor cancers at the Annual Meeting of the American Society of Clinical Oncology (ASCO). Several highlighted presentations provided new information on the activity of THALOMID in a wide range of solid tumor cancers including renal cell carcinoma, prostate cancer and malignant melanoma. In the last several weeks, investigators have presented data from over 170 clinical trials of THALOMID and REVIMID(TM) (CC-5013) at major medical meetings including the International Symposium on Myelodysplastic Syndromes and the International Multiple Myeloma Workshop and ASCO.

"Leading clinical investigators presented preliminary clinical data at ASCO on THALOMID in combination with chemotherapy, which substantiates further clinical investigation in a wide range of solid tumor cancers," said Sol J. Barer, Ph.D., President and Chief Operating Officer of Celgene Corporation. "Celgene plans to expand clinical trials of THALOMID and seek regulatory approval to provide a potential treatment for cancer patients affected with solid tumor cancers."

THALOMID in Combination with IL-2 for Metastatic Renal Cell Carcinoma
Robert J. Amato, D.O. of Baylor College of Medicine presented data from a Phase II study of THALOMID in combination with Interleukin-2 (IL-2) for the treatment of metastatic renal cell carcinoma. Thirty-seven patients received 400 mg/day of THALOMID plus IL-2 7m IU/m2 days one-five, weeks one-four. All patients had prior nephrectomy and had an average of three metastatic sites (range: one to five). Of 36 evaluable patients, two (six percent) achieved a complete response, 11 (31 percent) achieved a partial response and six (17 percent) experienced disease stabilization. Dr. Amato also presented data from a completed Phase I study of THALOMID plus IL-2 in metastatic renal cell carcinoma. In the Phase I study, 15 patients received a daily THALOMID dose of 200 mg (three patients), 400 mg (six patients) or 600 mg (six patients). IL-2 was administered by subcutaneous injections of 7 mIU/m2 on days one-five, weeks one-four. Of the 15 patients, one (7 percent) achieved a complete response, five (33 percent) achieved a partial response and two (13 percent) achieved disease stabilization. Dr. Amato reported that the combined results of both the Phase I and Phase II trial demonstrated that twenty-seven of fifty-one patients (53 percent) treated in both trials achieved either an objective response or disease stabilization. In addition, the three patients who achieved a complete response continue to respond on therapy at longer than 15, 17 and 19 months. Patients who experienced a partial response to therapy achieved overall survival of four to longer than 23 months and patients who experienced stable disease achieved overall survival of ten to longer than 24 months. Adverse events observed during the trials were sedation, fatigue, constipation, skin rash, deep venous thrombosis, fluid retention, flu-like symptoms, bradycardia and neuropathy.

THALOMID in Combination with Paclitaxel and Estramustine in Androgen Independent Prostate Cancer
Danai Daliani, M.D. of M.D. Anderson Cancer Center presented data from a Phase I/II study of THALOMID with weekly Paclitaxel and Estramustine. Dr. Daliani initiated the trial to investigate if THALOMID plus Paclitaxel and Estramustine had incremental anti-tumor activity in androgen independent prostate cancer patients who had progressed after prior chemotherapy. Dr. Daliani and her colleagues determined that 30 percent of patients achieving a greater than 50 percent PSA (prostate specific antigen) decline would define a clinically significant event. During the trial, 30 patients received 100 - 600 mg/day of THALOMID as tolerated, 80-100 mg/m2 Paclitaxel on days three and ten and 140 mg of Estramustine days one-five and eight-twelve. Of 25 evaluable patients, three patients (12 percent) experienced a PSA decline of at least 80 percent, 15 patients (60 percent) experienced a PSA decline of 50-79 percent and five patients (20 percent) experienced a stabilization in PSA levels. Based on the data, Dr. Daliani concluded that the PSA responses exceeded the threshold for clinical significance. Adverse events observed were grade one neuropathy and thromboembolic events. One patient experienced grade three neutropenia and two patients developed pneumonia.

THALOMID Plus Temozolomide in Patients with Metastatic Melanoma
Wen-Jen Hwu, M.D., Ph.D. and colleagues from Memorial Sloan-Kettering Cancer Center presented Phase II data on THALOMID in combination with temozolomide in melanoma patients with measurable brain metastasis. Twenty-four patients with progressive intracranial metastasis were enrolled. Temozolomide was administered daily at 75 mg/m2 for six weeks followed by a two-week break. Patients younger than 70 years were started on 200 mg/day of THALOMID escalated by 100 mg every two weeks to a maximum dose of 400 mg/day. Patients older than 70 years were started on 100 mg/day of THALOMID escalated by 50 mg every week to a maximum dose of 250 mg/day. Thirteen patients completed at least one cycle of therapy (range: one to four) and 11 patients were evaluable for brain response. Of the 11 evaluable patients, two (18 percent) achieved a complete response, one (nine percent) experienced a partial response and five (45 percent) experienced stable disease. Median follow-up among survivors was 7.5 months (range: greater than three -- greater than 24) and median survival for all patients was 5 months. Adverse events observed during the trial were tremors, neurosensory, thrombosis, nausea, myalgia, flatulence, neuromotor, edema and lyphopenia. This study has been accepted for publication in an upcoming issue of the Journal of Clinical Oncology.

About Renal Cell Cancer
Renal cell carcinoma is the most common form of kidney cancer, caused when cells in the lining of the renal tubule undergo cancerous changes. The American Cancer Society estimates that about 31,000 new cases of kidney cancer (18,000 men and 13,000 women) are diagnosed in the United States annually. About 12,000 people die from this disease each year. Unlike other cancers, kidney cancer doesn't respond to chemotherapy, since one of the major functions of the kidneys is to clear the body of the toxins. The only approved drug for the treatment of metastatic kidney cancer in the United States is Interleukin-2 (IL-2).

About Prostate Cancer
Prostate cancer is the most common type of cancer found in American men, other than skin cancer. According to the American Cancer Society, it is estimated that there are approximately 190,000 new cases of prostate cancer in the United States each year. About 30,000 men will die from this disease and prostate cancer is the second leading cause of cancer death in men, exceeded only by lung cancer.

About Metastatic Melanoma
Melanoma skin cancer begins in the cells that produce skin coloring (melanocytes) and accounts for about four percent of skin cancer cases, but causes about 80 percent of skin cancer deaths. The number of new cases of melanoma in the Unites States is on the rise. The American Cancer Society estimates that 54,000 new cases of melanoma will be diagnosed this year and that about 7,500 people will die.

Safety Notice
If thalidomide is taken during pregnancy, it can cause severe birth defects or death to an unborn baby. Thalidomide should never be used by women who are pregnant or who could become pregnant while taking the drug. Even a single dose, one capsule (50 mg, 100 mg and 200 mg), taken by a pregnant woman can cause severe birth defects. Because thalidomide is present in the semen of male patients, males receiving thalidomide must always use a latex condom during sexual contact with women of childbearing potential even if he has undergone a successful vasectomy. Thalidomide can only be marketed under a special restricted distribution program. This program is called the "System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.(R)). Under this program, only registered prescribers and pharmacists may dispense the drug. In addition, patients must be advised of, agree to and comply with the requirements of S.T.E.P.S.

Thalidomide is known to cause nerve damage that may be permanent. Peripheral neuropathy is a common, potentially severe, side effect of treatment with thalidomide that may be irreversible. Decreased white blood cell counts, including neutropenia, have been reported in the clinical use of thalidomide. In placebo controlled clinical trials of HIV-seropositive patient populations, there have been reports of increased plasma HIV RNA levels associated with thalidomide therapy. The most common adverse events observed in clinical use in ENL and HIV-seropositive patient populations are rash, maculo-papular rash, drowsiness/somnolence, peripheral neuropathy, dizziness/orthostatic hypotension, neutropenia, and increased HIV-viral load. Patients should be advised about these associated adverse events and routinely monitored by a physician during treatment with thalidomide.

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