Abstract
Intermittent androgen suppression (IAS) therapy for prostate cancer patients attempts to maintain the hormone dependence of the tumor cells by cycles alternating between androgen suppression (AS) and treatment cessation till a certain prostate-specific antigen (PSA) threshold is reached. Side effects are expected to be reduced, compared to standard continuous androgen suppression (CAS) therapy. The present study examined the effect of IAS on bone metabolism by determinations of serum procollagen I N-terminal peptide (PINP), a biochemical marker of collagen synthesis. A total of 105 treatment cycles of 58 patients with prostate cancer stages ≥pT2 was studied assessing testosterone, PSA and PINP levels at monthly intervals. During phases of AS lasting for up to nine months PSA levels were reversibly reduced, indicating apoptotic regression of the prostatic tumors. Within the first cycle PINP increased at the end of the AS period and peaked in the treatment cessation phase. During the following two cycles a similar pattern was observed for PINP, except a break in collagen synthesis as indicated by low PINP levels in the first months off treatment. Therefore, measurements of the serum PINP concentration indicated increased bone matrix synthesis in response to >6 months of AS, which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses. In summary, synthesis of bone matrix collagen increases while degradation decreases during off-treatment phases in patients undergoing IAS. Although a direct relationship between bone matrix turnover and risk of fractures is difficult to establish, IAS for treatment of biochemical progression of prostate tumors is expected to reduce osteoporosis in elderly men often at high risk for bone fractures representing a highly suitable patient population for this kind of therapy.
Highlights
Prostate cancer is among the most common types of malignancies and causes of cancer-related deaths in men worldwide
Measurements of the serum procollagen I N-terminal peptide (PINP) concentration indicated increased bone matrix synthesis in response to >6 months of androgen suppression (AS), which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses
Intermittent androgen suppression (IAS) was proposed as a novel clinical concept assuming that tumorigenic stem cells are residing in an androgen-sensitive state during limited regrowth in treatment cessation periods [6,7]
Summary
Prostate cancer is among the most common types of malignancies and causes of cancer-related deaths in men worldwide. Treatment traditionally consists of androgen suppression (AS) of the growth of cancer cells either by orchidectomy or the use of LHRH analogs and steroidal or nonsteroidal antiandrogens, respectively [3]. Continuous androgen suppression (CAS) controls tumor growth for only two to three years until hormone-resistant cancers, which respond poorly to any further therapy including treatment with chemotherapeutics, appear [4,5]. Intermittent androgen suppression (IAS) was proposed as a novel clinical concept assuming that tumorigenic stem cells are residing in an androgen-sensitive state during limited regrowth in treatment cessation periods [6,7]. Since regrowing tumors in patients undergoing IAS were consistently shown to be sensitive over several cycles of androgen withdrawal and this kind of therapy resulted in improved quality of life [7,8,9]. Phase III studies established IAS as therapy equivalent to CAS in respect to survival leading to the proposal of IAS as standard therapy for progressive prostate cancer [10,11]
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