15639 Background: As single agent GEM is a standard therapy for APC. CDDP is the oldest platinum compound which appears to be active in the treatment of this cancer. GEM has demonstrated activity in combination with various CDDP regimens. A pooled retrospective analysis revealed that GEM plus CDDP compared with GEM increased OS and PFS. We evaluated safety, feasibility and efficacy of GEM plus CDDP (24 hours infusion) every 2 weeks in APC pts. Methods: From 2/2005 to 12/2006 37 pts entered in the study (male/female = 25/12), median age was 61 yrs (range 40–77), median ECOG performance status was 0/13 pts - 1/19 pts - 2/5 pts), predominant metastatic site was liver in 19 pts, lung in 7pts, 31 pts had metastatic diasease (8 pts were in relapse). Pain was reported at diagnosis in 21 pts. Comorbidity were diabetes in 10 pts, prior solid tumour in 4 pts, prior myocardial infarction in 2 pts. Median number of cycles was 8 (range 1 - 10), total number of cycles was 267. Schedule of treatment: GEM 1,250 (10 mg/m2/min infusion) day 1, CDDP 40 mg/m2 24 hours infusion day 1, hydratation with saline solution was administered to prevent renal failure. Cycles were repeated every 2 weeks. To prevent nausea and vomiting, 5-hydroxytryptamine-3 antagonists (5HT3) IV plus dexamethasone 12 mg IV were administered before chemotherapy and oral 5HT3 were given orally at standard doses for 2 days after chemotherapy. Results: We observed no CR, 6 PR (16%) and 20 SD (54%), 17 (46%) pts were alive 12 months after the beginning of chemotherapy and 17% after 18 months. Median OS was 12.5 months (range 2–42). Hematologic toxicity G3–4 was neutropenia in 8.1% of pts, anemia in 8.1% of pts, thrombocytopenia in 2.7% of pts. Nonhematologic toxicity was nausea/vomiting G2 in 5.4% of pts, mucositis/diharrea in 2.7% of pts, renal toxicity G2 in 2.7% of pts. No toxic death was reported. Conclusions: The addition of CDDP (c. i.) to GEM in pts with APC is feasible and safe; median survival was similar to what observed with other combinations of two or more cytotoxic drugs; the treatment is not expensive (150 euro/cycle). No significant financial relationships to disclose.
374 Background: Administration of carboplatin AUC 7 has become a standard adjuvant option to be discussed with pts following orchiectomy for stage I seminoma, as alternative to radiotherapy on retroperitoneal lymphnodes or observation. The toxicity of AUC 7 carboplatin appeared manageable in the pivotal trial by Oliver et al. (Lancet, 2005), but dose ranges were not reported. Oncologists use different methods to estimate GFR and to calculate this unusually high dosage of carboplatin, and fear of toxicity may induce arbitrary dose reductions and potentially compromise the outcome. Methods: In 9 Italian centers we conducted a retrospective review focusing on adjuvant carboplatin administration to stage I seminoma pts. Modality of dose calculation, dose reductions and toxicities were recorded. Results: Since August 2006, 100 pts have been treated, median age 35 years (range 26 to 58). Adverse prognostic factors were either T >4 cm (14% of pts) or rete testis invasion (32), both (36), none or unspecified (18). Glomerular Filtration Rated was estimated mainly by Cockroft-Gault formula (55% of pts), Jeliffe formula (27%), 24-hour urine collection (17%), MDRM (1%): median value was 106 ml/min (range 75 to 209). All Oncologists declared to use Calvert formula to calculate AUC 7 dose, and administered a median of 900 mg of carboplatin (range 690 to 1535). A dose reduction > 10% was prudentially applied to 15% of pts; a second cycle was delivered in 8 pts. Acute toxicities are outlined in table 1. After a median follow-up of 20 months, 6% of patients have relapsed (all in the retroperitoneum), none of whom had been treated with reduced dose. Conclusions: AUC 7 carboplatin dosage peaked 1,535 mg in our cohort of stage I seminoma patients with no infections and nephrotoxicity, moderate nausea-vomiting, but 5% of grade 3-4 thrombocytopenia. Prudential dose reductions appeared unfrequent and should be proscribed. [Table: see text]
The development of a neuroendocrine phenotype as a mechanism of resistance to hormonal treatment is observed in up to 20% of advanced prostate cancer patients. High grade neuroendocrine prostate cancer (NEPC) is associated to poor prognosis and the therapeutic armamentarium is restricted to platinum-based chemotherapy. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) imaging has recently emerged as a potential new standard for the staging of prostate cancer and PSMA-based radioligand therapy (RLT) as a therapeutic option in advanced metastatic castration resistant prostate cancer (mCRPC). PSMA-based theranostic is not currently applied in the staging and treatment of NEPC since PSMA expression on neuroendocrine differentiated cells was shown to be lost. In this case series, we present 3 consecutive mCRPC patients with histologically proven high grade neuroendocrine differentiation who underwent PSMA-PET/CT and surprisingly showed high tracer uptake. This observation stimulates further research on the use of PSMA-based theranostic in the management of NEPC.
158 Background: ECHOS trial is a large real-world study, which is collecting data on mCSPC patients treated in the daily clinical practice in Italy from 2015. To date, > 1500 pts were included in the study, most of them treated with DOC, according to the availability of the active agents over the time in Italy. In the present analysis, we assessed the characteristics and outcomes of mCSPC pts progressing within 6 mos from the start of DOC. Methods: We retrospectively and prospectively reviewed the clinical records of a consecutive series of mCSPC pts treated with DOC in the daily clinical practice in 69 Italian Hospitals. The treatment mostly consisted of DOC at the standard dose of 75 mg/sqm every 3 wks for six courses. For each pt we recorded the pre and post-DOC clinical history, the baseline characteristics of the pts, the treatment details and clinical outcomes. For the purpose of the present study, we considered only pts who ended chemotherapy by September 2022. PR was defined as the onset of progressive disease within 6 mos from the DOC start. Results: Among 920 mCSPC pts treated with DOC, 122 (14.3%) were PR. Most of them (95.6%) presented a de novo (DN) disease, which showed mostly high volume (HV) features (82.3%). Compared to the pts without PR, those showing PR presented more frequently a visceral involvement (26.2% vs 18.2%; p = 0.038), had lower baseline levels of hemoglobin (12.8 g/dl vs 13.4 g/dl; p < 0.0001), and higher baseline levels of lactate dehydrogenase (266 U/L vs 220,5 U/L; p < 0.002). No other significant differences were observed in terms of baseline PSA and alkaline phosphatase levels, symptoms degree, disease volume and timing of mets presentation between PR e no-PR pts. The median number of life prolonging agents administered after DOC progression was 1 in pts with PR as well as in pts without PR. The median overall survival was 11.9 mos and 44.9 mos in PR and no-PR pts, respectively (p < 0.0001). Conclusions: Our data suggest that PR led a significant worsening of prognosis with a relevant shortening of life expectancy in pts who receive DOC for mCSPC.
Abstract Background It is not clear whether changes in body composition induced by androgen deprivation therapy (ADT) in prostate cancer (PC) patients are uniform or vary in the different body districts and whether regional lean body mass (LBM) and fat body mass (FBM) could have an impact on bone health. Objective To prospectively evaluate the regional changes in LBM and FBM in PC patients submitted to degarelix; to explore the relationship of regional body composition and bone mineral density (BMD) and bone turnover markers. Design, setting, and participants 29 consecutive non metastatic PC patients enrolled from 2017 to 2019. FBM, LBM and bone mineral density (BMD) evaluated by dual-energy x-ray absorptiometry (DXA) at baseline and after 12-month of ADT. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) assessed at baseline, 6 and 12 months. Intervention All patients underwent degarelix administration. Outcome measurements and statistical analysis T -test or sign test and Pearson or Spearman test for continuous variables were used when indicated. Results and limitations Median percent increase in FBM ranged from + 14.5% in trunk to + 25.4% in the left leg after degarelix. LBM changes varied from + 2% in the trunk to − 4.9% in the right arm. LBM in both arms and legs and their variations after degarelix directly correlated with ALP and inversely correlated with CTX. Lean mass of limbs, trunk and legs significantly correlated with BMD of the hip, lean mass of the trunk significantly correlated with spine BMD. These are post-hoc analysis of a prospective study and this is the main limitation. Conclusions an heterogeneous change in body composition among body district is observed after ADT and bone turnover is influenced by lean mass and its variation. A supervised physical activity is crucial to maintain general physical performance and preserving bone health.
data that hypovitaminosis D is a reliable prognostic parameter or that the outcome of patients with PC might be improved by vitamin D supplementation. Several drawbacks hamper the clinical interpretation of serum vitamin D levels in cancer: the hormonal activity of vitamin D is mediated by its binding to vitamin D receptor (VDR) within the cell nuclei, and both VDR expression and VDR polymorphisms reflect the individual susceptibility to vitamin D action 3 ; and hypovitaminosis D is associated with secondary hyperparathyroidism, which could have contributed tothe negative prognostic features observed. Parathyroid hormone (PTH), in fact, is similar to PT-related peptide, which is a potent growth factor, and both PTH and PT-related peptide interact with the same receptor that is expressed by PC cells. 4 In the study by Nyame et al, 1 neither tissue VDR and its relevant polymorphisms nor serum PTH were measured; therefore, information on the interaction between vitamin D status and these important biologic parameters is lacking. Moreover, the assays to determine serum vitamin D levels are not standardized, and a significant variability among methods and laboratories was reported. 5 This further complicates the application of the results of the Nyame et al 1 study to clinical practice. In their discussion, Nyame et al 1 stated that patients with PC with intermediate risk may benefit, in terms of disease outcome, from the normalization of vitamin D levels. In principle, we agree with the authors that future studies are warranted to assess the efficacyofvitaminD supplementationin terms ofPC aggressiveness. However, caution should be taken in administering vitamin D to patients with PC outside a clinical trial. In fact, the results of a prospective phase III clinical trial testing the efficacy of high-dose calcitriol plus docetaxel versus single-agent docetaxel in men with castrate-resistant metastatic PC showed a shorter survival in the vitamin D arm compared with the control arm. 6
