The Use of Triethylenethiophosphoramide (Thio-TEPA) in the Treatment of Metastatic Carcinoma of the Breast

Twenty-two patients with metastatic breast cancer were treated by a combination of testosterone and N,N′,N″, triethylenethiophosphoramide (Thio-TEPA). All had undergone mastectomy and received radiation; six had had an oophorectomy and 12 had had oophorectomy and adrenalectomy. For its marrow-stimulating effect testosterone was given intramuscularly, 100 mg. daily for five days; then 100 mg. of depo-testosterone was given intramuscularly once a week. On the sixth day of treatment, 15 mg. of Thio-TEPA was given intramuscularly and repeated daily or every second day until a definite depression of the leukocyte and/or platelet counts occurred. To 15 patients a total dose of 200 mg. or more of triethylenethiophosphoramide was given. Thirteen patients improved subjectively and five of these improved objectively. The duration of improvement varied between one and 12 months. Treatment was most effective in patients with bony metastases.     

Emerging Therapeutic for the Treatment of Skeletal-related Events Associated With Metastatic Castrate-resistant Prostate Cancer

Prostate cancer is the most prevalent cancer in US and European men and the second leading cause of cancer death in those populations. It is somewhat unique in that nearly all patients who succumb to the disease will ultimately develop bone metastasis. Morbidity from bone metastasis-referred to as skeletal-related events, which include fractures, cord compression, radiation to bone, and surgery to bone—leads to significant costs and impaired quality of life. This article reviews three agents and the roles they play in the ever-changing armamentarium of treatments for metastatic castrate-resistant prostate cancer (mCRPC). The potential benefits of these agents are discussed, as well as the continuing use of these agents and their earlier introduction in the patient with progressive mCRPC with bone metastasis.Key words: Metastatic castrate-resistant prostate cancer, Skeletal-related events, Bone metastasis, Zoledronic acid, Denosumab, Radium Ra 223 dichlorideProstate cancer is the most prevalent cancer in US and European men and the second leading cause of cancer death in those populations. It is somewhat unique in that nearly all patients who have the disease will ultimately develop bone metastasis.¹ Morbidity from bone metastasis—referred to as skeletal—related events (SREs), which include fractures, cord compression, radiation to bone, and surgery to bone-leads to significant costs and impaired quality of life. An estimated 241,740 men are diagnosed with prostate cancer each year in the United States¹; between 9.5% and 17.8% of these patients have M0 + M1 castrate-resistant prostate cancer (CRPC).^2,3Skeletal tumor burden and fracture are both independent predictors of death in men with metastatic CRPC (mCRPC).^2,3 In addition, pain is an independent prognosticator for death⁴; thus, agents that reduce pain may improve quality as well as quantity of life. In the past decade, three new agents have been approved in the United States for the treatment and/or prevention of SREs in men with mCRPC. However, urologists continue to under-treat this condition.⁵ A recent clinical trial that screened a large population of men thought to have CRPC without metastasis found nearly one third of patients to have metastatic prostate cancer.⁶ And a recent large clinical trial in men with mCRPC, most of whom had bone metastases, showed fewer than 50% of patients were receiving a bisphosphonate.⁷This article reviews these three agents and the new roles they play in the ever-changing armamentarium of treatments for mCRPC. The potential benefits of these agents are discussed, as well as the continuing use of these agents and their earlier introduction in the patient with progressive mCRPC with bone metastasis.