Dramatic decline in prostate-specific antigen by withdrawal of estramustine phosphate in hormone refractory prostate cancer

Prostate-specific antigen (PSA) decline after discontinuation of estramustine phosphate (EMP) is extremely rare. We report a case with dramatic PSA decline after withdrawal of EMP. A patient with prostate cancer had been treated with luteinizing hormone-releasing hormone and EMP. After refractory, EMP was withdrawn. After withdrawal of EMP, PSA dramatically decreased from 214 ng/mL to 3.71 ng/mL (98.5% decline) and remained low for more than 17 months. In association with PSA decline, lumbago and metastatic lesions improved. We should be aware of this phenomenon and the discontinuation of EMP is recommended in patients with rising PSA after an initial response to EMP.     

Alternative antiandrogen therapy in patients with castration‐resistant prostate cancer: A single‐center experience

Outcomes of alternative (second‐line) antiandrogen therapy in 112 patients with relapsing prostate cancer after first‐line hormonal therapy were analyzed. A good response (prostate‐specific antigen [PSA] decrease ≥50%) and a partial response (PSA decrease of 0–50%) by switching from bicalutamide (BCL) to flutamide (FLT) and from FLT to BCL were achieved in 35.4% (28/79) and 30.4% (24/79), and in 45.0% (9/20) and 20.0% (4/20) of cases, respectively. A good response and a partial response with the change from chlormadinone acetate (CMA) to a non‐steroidal antiandrogen (FLT or BCL) and from a non‐steroidal antiandrogen to CMA were obtained in 25.0% (2/8) and 37.5% (3/8), and in 20.0% (1/5) and 0% (0/5) of cases, respectively. In multivariate analyses, a second‐line good response was significantly predictive of cause‐specific survival from first therapy relapse to cancer death in all patients. Patients (52/112, 46.4%) with ≥30% decrease in PSA levels were associated with significantly better cause‐specific survival as measured from the start of first‐line treatment and first‐line relapse.     

Clinical features of prostate cancer patients younger than 50 years: Report of seven cases

BACKGROUND: The incidence of prostate cancer increases with age and latent cancer is common in older men. But clinical prostate cancer is rare in men aged < 50 years. METHODS: Between 1988 and 2000, we studied seven cases of prostate cancer in men aged under 50 years. The clinicopathological results included: the first sign or symptom; prostate-specific antigen (PSA) at the time of diagnosis; existence of abnormal digital rectal examination (DRE); the differentiation of the cancer and Gleason score; and the outcome of treatment. RESULTS: Six cases were diagnosed as stage D2. One case was diagnosed as stage B2 and the patient underwent radical prostatectomy. None of the cases were detected by mass screening. The PSA at diagnosis was < 10 ng/mL in only one case and that patient underwent radical prostatectomy. Six cases were diagnosed pathologically as poorly differentiated adenocarcinoma. The only patient who survived more than 5 years underwent radical prostatectomy. CONCLUSION: Six of seven cases of prostate cancer were detected at advanced stage. Only one case was thought to be curable and this patient's cancer was detected by chance occult blood test. Because young prostate cancer patients are potential candidates for radical prostatectomy and the sensitivity of PSA might be higher in young men, high-risk groups could be screened by PSA.     

Effects of the somatostatin analog lanreotide on the circulating levels of chromogranin-A, prostate-specific antigen, and insulin-like growth factor-1 in advanced prostate cancer patients

BACKGROUND: The concept that neuroendocrine cells detected within prostate adenocarcinoma produce paracrine factors, that may exert a proliferative effect on exocrine prostate tumor cells, provides a rationale for the use of somatostatin analogs with the aim to counteract or delay the tumor progression. This study was designed to provide preliminary information on the effect of the administration of a long-acting somatostatin analog, lanreotide, on plasma levels of chromogranin A (CgA). Secondary aims were the evaluation of changes in circulating prostate-specific antigen (PSA) and insulin-like growth factor-1 (IGF-1). METHODS: Lanreotide (Ipstyl 30 mg; Ipsen, Milan, Italy) was administered intramuscularly every 14 days for 2 months to nine heavily pretreated prostate cancer patients with hormone refractory disease. All patients had, at baseline conditions, CgA values above the normal range. Androgen deprivation was maintained during the study period, while other concomitant antineoplastic treatments were not allowed. Serum PSA levels and plasma CgA and IGF-1 values were measured every week. RESULTS: Lanreotide treatment was very well tolerated and no patient experienced major toxicity. Plasma CgA values at baseline: mean 109 U/liter, standard deviation +/- 85 decreased significantly after treatment as follows: 42 U/liter, +/- 17.8; 27.2 U/liter +/- 13.6; 31.4 U/liter, +/- 17.8 and 27.6 U/liter, +/- 17.0; after 7, 14, 21, and 28 days, respectively (P < 0.01, Friedman ANOVA). Serum PSA did not change. Baseline IGF-1 was found to be above the detection limit in four cases, all of them showing a decrease after lanreotide. CONCLUSIONS: Lanreotide administration to prostate cancer patients induces a decrease in plasma CgA and IGF-1 levels, without any influence on serum PSA values. Prostate 47:205-211, 2001.     

Similar rates of exponential decrease in serum concentrations of free prostate-specific antigen (PSA), PSA complexed to alpha-1-antichymotrypsin, and human glandular kallikrein 2 (hK2) in prostate cancer patients treated with GnRH-analogues

BACKGROUND: Our recently reported finding of rapid bi-exponential elimination of free prostate-specific antigen (PSA) after radical retropubic prostatectomy in patients with moderately elevated PSA levels, which contrasted a very slow, linear elimination of PSA complexed to alpha-1-antichymotrypsin (ACT), prompted us to study whether these elimination rates were applicable for patients selected for castration treatment with very high pretreatment concentrations of PSA in serum. In addition, serum concentrations of hK2, the activator of proPSA, were measured. METHODS: Pretreatment serum was obtained from 21 previously untreated prostate cancer patients due for hormonal treatment with a GnRH-analog. Samples were also collected during treatment up to a minimum of 24 weeks at 2-week intervals and analyzed with immunofluorometric assays for free PSA (PSA-F), PSA complexed to alpha-1-antichymotrypsin (PSA-ACT), total PSA (PSA-T), and human kallikrein 2 (hK2). For pharmaco-kinetic analysis the serum concentrations of hK2 and PSA forms for each patient were plotted against time both before and after logarithmic transformation and the half-lives were calculated as ln2/k. RESULTS: Median pretreatment serum concentrations were 322 ng/ml (range, 1.9-2210) for PSA-T, 27.8 ng/ml (range, 1.14-259) for PSA-F, and 207 ng/ml (range, 0.8-2080) for PSA-ACT. All patients had castrate levels of serum testosterone (< 2.5 nmol/l) in less than 21 days after initiation of GnRH-analog treatment. It was possible to evaluate data from 19/21 patients which showed an exponential decrease of all PSA concentrations in serum, with mean half-lives of 12.9 days (range, 7.3-30) for PSA-T, 15.5 days (range, 7.7-37.5) for PSA-F, and 12.3 days (range, 6.6-30) for PSA-ACT. Median pretreatment percent free PSA (PSA-F/PSA-T) was 12% compared to 18% at nadir. The median pretreatment level of hK2 was 3.5 ng/ml (range, 0.29-30.3). There was an exponential decrease in hK2 concentrations in serum after initiation of hormonal treatment with a mean half-life of 18.7 days (range, 7.5-37.5). CONCLUSIONS: For the majority of patients with hormonally treated prostate cancer the serum concentrations of PSA-T, PSA-F, PSA-ACT, and hK2 decreased slowly in parallel and mono-exponentially after initiation of treatment. Mean half-lives were between 12 and 19 days.     

Obese African‐Americans with prostate cancer (T1c and a prostate‐specific antigen,PSA, level of <10 ng/mL) have higher‐risk pathological features and a greater risk of PSA recurrence than non‐African‐Americans

Study Type – Prognosis (retrospective cohort)
Level of Evidence 2b

OBJECTIVE

To analyse the relationship between African American (AA) race and obesity in men with prostate cancer.

PATIENTS AND METHODS

In all, 4196 patients who underwent radical prostatectomy from 1988 to 2008 were identified in the Duke Prostate Center database. A subset of 389 (AA 20.9% and non‐AA 79.1%) patients with a body mass index (BMI) of ≥30 kg/m², T1c disease and a prostate‐specific antigen (PSA) level of <10 ng/mL were stratified by race and analysed. Age at surgery, race, surgical margin status, pathological tumour stage (pT2, pT3/4), pathological Gleason sum (<7, 3 + 4, 4 + 3, >7), extracapsular extension (ECE), seminal vesicle invasion and tumour percentage were assessed by univariate analysis followed by Cox regression analysis.

RESULTS

In the entire cohort, 143 (38.1%) AA men were obese, compared to 509 (25.0%) of the non‐AA men. AA men had a significantly higher tumour percentage (15% vs 10%, P= 0.002), and a greater proportion of pT3/4 disease (45.1% vs 26.2%, P= 0.039), pathological Gleason sum ≥7 (70.7% vs 50.5%, P= 0.003), positive ECE (37.8% vs 23.1%, P= 0.007), and positive surgical margin (52.4% vs 36.8%, P= 0.010) than non‐AA men. AA men had a greater risk of PSA recurrence on Kaplan Meier (P= 0.004) and Cox regression analysis (P= 0.040, hazard ratio 1.72)

CONCLUSION

A greater proportion of AA men was obese in this cohort. Obese AA with impalpable cancer and a PSA level of <10 ng/mL have a higher risk of pathological features than obese non‐AA men, as well as a higher risk of PSA recurrence. Obesity might be responsible for the racial disparity seen in prostate cancer.     

Phase II study of liposome-encapsulated doxorubicin plus cyclophosphamide,followed by sequential trastuzumab plus docetaxel as primary systemic therapy for breast cancer patients with HER2 overexpression or amplification

Purpose of the studyTrastuzumab combined with sequential chemotherapy with taxanes and anthracyclines as primary systemic therapy achieved high rates of pathologic complete response (pCR). Non-pegylated liposome-encapsulated doxorubicin (NPLD) has shown equal efficacy but minor cardiotoxicity compared to doxorubicin. This phase II study aimed to evaluate the activity and safety of trastuzumab with sequential chemotherapy for early or locally advanced HER2 positive BC.MethodsPreoperative treatment included NPLD (60 mg/mq iv) plus cyclophosphamide (600 mg/mq iv) every 3 weeks for 4 cycles followed by docetaxel (35 mg/mq iv) plus trastuzumab (4 mg/mq loading dose iv, then 2 mg/mq iv) weekly for 16 weeks. Primary endpoint was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes. Clinical staging was exploratory evaluated by CT-PET.Results43 pts were treated from december 2005 to September 2011, 39 of them were evaluable for the purpose of study. Median age was 53 years (range: 31–78), the majority of pts had tumour stage cT2 (63%), tumour grade 3 (86%), clinical nodes involvement N+ (77%), ER positive (56%) and Ki-67 ≥20% (77%). pCR was reported in 19 (49%) of 39 pts. There was an association between Ki-67 ≥20% at baseline and pCR (p = 0.018). No cardiac toxicity or discontinuation of trastuzumab was reported. CT-PET modified the clinical stage for 10 patients showing new loco-regional lymph nodes.ConclusionsThis study confirms that integrating anti-HER2 therapy in primary treatment for HER2 positive breast cancer is active. NPLD is a safe option to minimize cardiotoxicity.