bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II screening study of an LHRH analog, dexamethasone and somatostatin analog versus LHRH analogue with dexamethasone in HRPC
Authors: Calais da Silva F. M. , Calais da Silva F. E. , Gonçalves F. , Oliver T. 
Published: March 2020

15579 Background: As far as prostatic cancer is concerned, we know that somatuline (SMS) blocks GH, PRL, tissular growth factors (TGF) and that it has a direct antiproliferative cellular growth effect. The simultaneous administration of depot forms of SMS and LHRH analogues induced the greatest decrease in tumor growth. Methods: A randomised Phase II trial was carried out in M0 (PSA ≥ 20 ng/ml) and M1 patients with hormone refractory prostate cancer to simultaneously screen decapeptyl and dexamethasone, both with and without SMS (120 mg every 4 weeks), with respect to the PSA response rate, time to PSA progression, duration of survival and toxicity. Results: 72 patients with a median PSA of 77 ng/ml were randomised by 3 centers, 35 to decapeptyl, dexamethasone, both with and without SMS (DDS) and 37 to decapeptyl and dexamethasone (DD). 18 of 33 (54%) patients on DDS and 13 of 32 on DD (43%) had a PSA response (a decrease of at least 50% as compared to baseline). The median time to PSA was 5.5 months in the SMS group and 1.9 months in the group without SMS. At 6 months, 45.7% were PSA progression free in the SMS group versus 35.1% in the goup without SMS. The median time to PSA progression in PSA responders was 10.6 months in the SMS group and 13.9 months in the group without SMS. At 6 months, 73.7% of the PSA responders were progression free in the SMS group versus 81.3% in the group without SMS. 45 patients died (62.5%), 22 (62.9%) in the SMS group and 23 (62.2%) in the group without SMS. 15 and 19 of the deaths respectively were due to prostate cancer. The median duration of survival is 1.65 years in the SMS group and 1.48 years in the group without SMS. At 6 months, 85.7% were alive in the SMS group vs 78.1% in the group without SMS. At 12 months, 77.1% were alive in the SMS group vs 69.4% in the group without SMS. Conclusions: There is no evidence that SMS may have increased the incidence of side effects. The PSA response rate was slightly higher in the SMS group, 54% vs 43% and the median time to PSA progression in all patients appears to have been slightly longer in the SMS group. Fewer objective progressions were also observed in the SMS arm, 4 vs 12. These results suggest that SMS may add to the activity of decapeptyl and dexamethasone and thus have a role in the treatment of hormone refractory prostate cancer. No significant financial relationships to disclose.
Spontaneous otoacoustic emissions (SOAE) changes in testicular cancer patients treated with cisplatin: A pilot study of whether the acute ototoxic effect of cisplatin treatment can be detected
Authors: Biro K. , Noszek L. , Prekopp P. , Vehovszky K. , Nemeth E. , Nagyivanyi K. , Geczi L. , Gaudi I. , Bodrogi I. 
Published: March 2020

15581 Background: We studied the acute ototoxic effect of cisplatin in testicular cancer patients with two highly sensitive new methods for detecting high frequency hearing loss: distorsion product otoacoustic emissions (DPOAE), and spontaneous otoacoustic emissions (SOAE). Methods: Checking the acute effect, 32 (63 ears) testicular cancer patients (median age: 33 years, range: 16–59 years) were measured on the first day of their first cycle and after one week of their last cycle of cisplatin treatment. 20 mg/m2 cisplatin was administered for five days, in BEP chemotherapy regimen. The patients got on the average 2.19 cycles (2–3 cycles). We also measured the SOAE of ten healthy control persons (without chemotherapy) matching sex and age distribution of this group. A detailed medical history evaluated audiological risk factors and hearing problems. Tympanometry, DPOAE and SOAE were measured, to detect the acute changes in the inner ear after low cumulative dose of cisplatin treatment. Paired t-test, and sign test was used for statistical analysis. Results: The DPOAE did not show any changes close after cisplatin treatment (average: 2.19 cycles, 2–3 cycles), similarly to our earlier results with pure tone audiometry (PTA) and transiently evoked otoacoustic emission (TOAE). But the SOAE showed significant, early changes in incidence, shape and amplitude, in the treated group. 66% of the SOAE changed after treatment (p=0,006). In the control group (20 ears) the SOAE never changed in a three months period. (It behaves as a fingerprint) Conclusions: DPOAE did not change significantly after 2 or 3 cycles of cisplatin treatment, similarly to our earlier results with PTA, and TOAE, but the change of the SOAE-incidence, shape and amplitude close after cisplatin treatment shows acute changes in the inner ear function (first described in the literature) after administration of low cumulative dose of cisplatin. This case is the first indication of the possible clinical relevance of SOAE. Our observation has to be confirmed in further studies, with larger number of patients. No significant financial relationships to disclose.
A phase I study of testosterone in patients (pts) with early castrate resistant prostate cancer (CRPC)
Authors: Knight D. A. , Mohile S. G. , Posadas E. M. , Manchen E. A. , Stadler W. M. 
Published: March 2020

15584 Background: Transition to the castrate resistant state may be due, in part, to the development of a more sensitive and promiscuous androgen receptor (AR) pathway. Androgen therapy of CRPC leads to growth arrest and tumor shrinkage in preclinical models. Historical studies of exogenous testosterone in pts is limited. This study was designed to determine toxicity of a transdermal testosterone therapy (Androderm [A]) in early CRPC. Methods: Pts with progressive PSA increases following androgen ablation and antiandrogen therapy with minimal or no bone metastases (Bone Scan Index of < 1.4%) and no visceral metastases were eligible. Pts were randomized to treatment with 2.5, 5.0, or 7.5mg/day of A and LHRH agonist treatment was maintained. Toxicity was evaluated every 2 weeks and all subjects underwent laboratory, quality of life (UCLA Prostate Cancer Index), and hand grip strength testing at baseline and week 6. Treatment was discontinued for severe toxicity, radiologic progression, or a 3-fold increase in PSA. Results: To date fourteen men were enrolled. Median baseline PSA was 10.9ng/mL (Range:5.3–63.6). Eight pts had no radiologic evidence of disease. Median on therapy testosterone levels (ng/dL) were 216 (n=4), 308 (n=5), 325 (n=5) for 2.5, 5.0, 7.5mg/day dose levels, respectively. Toxicities included grade 2 rash (n=1, dose 7.5), grade 2 hypertension (n=1, dose 7.5), grade 2 hypoglycemia (n=1, dose 5), and grade 2 anorexia (n=1, dose 5). In 29% of pts (n=4), there was a decrease in PSA (max decrease = 43%) from baseline lasting from 4 - 36 weeks; two sustained an initial rise before PSA decline. All other subjects required discontinuation of therapy due to PSA increase and/or radiological progression within 2–13 weeks; none of these patients sustained symptomatic progression of disease and PSA decreased in 8/11 pts with available data after therapy discontinuation. In this small sample, there were no significant differences between baseline and 6-week QOL and hand-grip scores. Conclusion: Testosterone treatment in early CRPC is feasible and safe, although use of PSA to assess anti-tumor effects is difficult. Further evaluation would require a randomized trial to evaluate time to progression and QOL endpoints. No significant financial relationships to disclose.
Adjuvant docetaxel chemotherapy with abbreviated hormonal therapy in patients with high-risk prostate cancer
Authors: Colocci N. , King C. R. , Brooks J. D. , Gill H. S. , Presti J. C. , Srinivas S. 
Published: March 2020

15589 Background: We conducted a pilot adjuvant docetaxel and abbreviated androgen deprivation study (ADT) in patients with high-risk localized prostate cancer. Study objectives were to evaluate toxicity, feasibility of 6 months of ADT and 3 months of docetaxel treatment, and incidence of serum PSA relapse at 2 years compared to historical controls. Methods: Eligible patients had radical prostatectomy or radiation therapy for high-risk disease (pathologic node positive disease, capsule involvement, extra-capsular extension, seminal vesicle involvement, positive surgical margins, Gleason score = 8, clinical stage T2c or T3, serum PSA >20, or pre-op PSA > 15 plus any high-risk feature). Patients were treated with taxotere 35 mg/m2 weekly 3 out of every 4 weeks for 3 months, and an LHRH analog for 6 months concurrently. In this high-risk cohort, we estimated the risk of PSA recurrence to be as high as 65% in 2 years. To detect a reduction in recurrence rates after surgery or radiation by 40% at a power of 80% and a 2-sided alpha of 0.05, a total of 21 patients were needed in this pilot Phase II study. Results: Twentyone patients were enrolled between 9/04–9/05. The median age was 59.5 years (48–72). Ten patients had a radical prostatectomy and 11 had radiation therapy. All patients received 6 months of LHRH analog therapy. Median pre- treatment PSA was 9.5 ng/ml (4–120). Mean Gleason grade was 8 (7–9); 65% of the patients had >50% biopsies positive. Treatment was well tolerated. Acute toxicity included 1 grade IV hyperglycemia. There was 1 dose reduction and 1 treatment delay. One patient had grade III elevation in serum AST which was transient. Grade I/II toxicities were common and included fatigue, diarrhea, insomnia, and pedal edema. Median follow up is 20 months. Five patients have relapsed. One (of 11) patients treated with radiation has relapsed with metastatic bone disease at 9 months. Four (of 10) patients who underwent prostatectomy have had a serologic relapse at 14, 14, 17 and 21 months, respectively. Conclusions: These data suggest that adjuvant weekly taxotere with abbreviated course of ADT is feasible and well tolerated. In this pilot trial, at a median follow up of 20 months, 23% of patients have relapsed. Longer follow up is required and is ongoing. No significant financial relationships to disclose.
Low molecular weight heparin (LMWH) increases the efficacy of immunotherapy in metastatic renal cell carcinoma patients with abnormal coagulation
Authors: Tsimafeyeu I. , Madzhuga A. , Demidov L. , Somonova O. , Kharkevich G. , Yelizarova A. , Petenko N. 
Published: March 2020

15591 Background: Antitumor effects of LMWH are unclear. Heparin can bind with fibroblast-growth factor, other heparine-binding angiogenic factors, their receptors, and/or impact on coagulation system which induces angiogenesis. We previously revealed hypercoagulation is a frequent symptom in metastatic renal cell carcinoma (MRCC) patients (pts) and clinically correlates with progression of the disease. Methods: Pts with MRCC and high level of fibrinogen, D-dimer or fibrin, antithrombin III and prothrombin were stratified by MSKCC prognostic criteria and included to receive immunotherapy plus LMWH (IL-2, 1 MIU, i.v, 3 tiw + IFN alpha, 5 MU, s.c, 3 tiw ± 5-FU 500 mg/m2, i.v. once a week, and Dalteparin, LMWH, 5000 IU, s.c, every day, for 3 weeks) or immunotherapy alone. Demographic and treatment characteristics were similar between both arms. The primary endpoint was cancer-related overall survival (OS). Results: Flu-like syndrome, hypotension, anorexia were most common side effects (CTC grade 1). There were no bleedings in LMWH group. Conclusions: These results demonstrate that Dalteparin significantly improves cancer specific overall survival and decreases disease progression rate in combination with immunotherapy in MRCC pts with abnormal coagulation. Phase II randomized multicenter open-label discontinuation trial will be conducted. [Table: see text] No significant financial relationships to disclose.
Phase II trial of oral imatinib in combination with every-three-week intravenous docetaxel in patients with metastatic, hormone- refractory prostate cancer
Authors: Appleman L. J. , Friedland D. , Chaussard C. , Gooding W. , Feinstein T. , Sulecki M. , Evans T. , Corgnati S. , Strausser H. , Chatta G. 
Published: March 2020

15603 Background: Imatinib is a small molecule tyrosine kinase inhibitor specific for Bcr-Abl, platelet-derived growth factor receptor (PDGFR) and c-Kit. Inhibition of PDGFR abrogates pericyte migration and perturbs regulation of interstitial fluid pressure, suggesting potential anti-tumor effect in combination with chemotherapy. Docetaxel is a microtubule-stabilizing cytotoxic agent shown to prolong survival in men with androgen-refractory prostate cancer (AIPC) when administered at 75 mg/m2 every 21 days. We have previously established that imatinib 400 mg daily plus docetaxel 60 mg/m2 every 21 days is well tolerated and now hypothesize that this combination will prolong time to disease progression (TTP) in patients with AIPC. Methods: Subjects with progressive AIPC received docetaxel 60 mg/m2 intravenously every 21 days (day 1; up to 8 cycles) plus imatinib 400 mg by mouth daily starting on day -3. After the first 6 subjects, the study treatment was modified so that subjects receive oral imatinib 400 mg only on days -3 thru +7 of each 21-day cycle. The primary endpoint is TTP. The sample size is 43 patients, providing 90% power to detect an increase in TTP from 5 to 8 months. Results: Nineteen subjects have enrolled in the study between August 2005 and October 2006. Age range of subjects was 54 to 84 years (median 69 years). Serious adverse events (=Grade (G) 3) were principally hematologic: neutropenia (G4=5, G3=2); thrombocytopenia (G4=1, G3=1), hemoglobin (G4=1). There was one G4 myocardial infarction and one incident of G5 sepsis associated with methicillin-resistant S. aureus bacteremia and normal neutrophil count. One instance each of the following G3 toxicities were observed: fatigue, myalgia, dyspnea, nausea/vomiting, diarrhea, chest pain, dizziness, urinary retention. Five subjects had >50% decrease in serum PSA. Eight subjects received 4 or more cycles of docetaxel, and 4 subjects continued on imatinib maintenance after completing 6–8 cycles of docetaxel plus imatinib. Conclusions: Intravenous docetaxel on day 1 plus oral imatinib on days -3 thru +7 of a 21-day cycle is generally well- tolerated in men with AIPC. Prolonged stable disease and/or serum PSA response was observed in several subjects. [Table: see text]
Delaying conformal radiation therapy in high-risk prostate cancer patients lowers the actuarial distant metastases free survival
Authors: Nakamura R. A. , Monti C. R. , Trevisan F. A. , Prestes J. C. , Cruz M. R. , Castilho L. N. , Reinato J. A. , Borges L. F. 
Published: March 2020

15614 Background: It is not well documented on medical literature the value of time to treat prostate cancer. This study was performed to evaluate the value of treatment time with conformal radiotherapy (3DCRT) in high-risk prostate cancer patients. Methods: From October 1997 to January 2002, 116 patients with high-risk prostate cancer were submitted to 3DCRT and were analyzed retrospectively. The median age was 65 years-old. High risk patients were defined as patients with PSA > 20 ng/ml, and/or T3 clinical stage and/or Gleason score > 7, or two factors of intermediate risk (PSA >= 10 and < 20 ng/ml, T2b-T2c and Gleason score = 7). The median time from diagnosis to 3DCRT was 2.9 months (0.9–134.9). The median doses of radiation on prostate and on seminal vesicles were 81 Gy (72–82.8) and 61.2 Gy (45–77.4), respectively. The neoadjuvant and concomitant androgen suppression therapy were performed on 69 (59.5%) and 79 (68.1%) patients, respectively. Results: On median follow-up of 54.5 months (13.5–93.9), the 5-year actuarial overall survival, the 5-year actuarial biochemical progression-free survival and the 5-year actuarial distant metastases free survival were 84.3%, 64.7% and 88.6%, respectively. The 5-year actuarial distant metastases free survival for patients treated with 3DCRT less than or equal to 5 months was 92.5% versus 72.1% for patients treated with 3DCRT > 5 months (p=0.0076). The 5-year actuarial distant metastases free survival for patients with biochemichal progression was 68.8% versus 100% for patients with no biochemical progression (p 65 years-old (p=0.0160). Conclusions: The study suggests that delaying 3DCRT in high-risk prostate cancer patients lowers the actuarial distant metastases free survival. Biochemical progression may be a strong prognostic factor for distant metastases and, consequently, poor quality of life. No significant financial relationships to disclose.
Perifosine (P), active as a single agent for renal cell carcinoma (RCC), now in phase I trials combined with tyrosine kinase inhibitors (TKI)
Authors: Stephenson J. , Schreeder M. , Waples J. , Hargis J. , Campos L. , Birch R. , Henderson I. 
Published: March 2020

15622 Background: P is an oral alkylphosphocholine with effects on multiple pathways including Akt, MAPK and JNK. Akt/S6 is often activated in RCC and associated with resistance. In a phase I study of P, 3/6 RCC patients (pts) had stable disease (SD) lasting for 4, 6 and 14 months (m). RCC was further assessed in a broad phase 2 trial, and subsequently, two phase 1 trials combining P with TKIs have been initiated. This is an update of the phase II and first report of the phase I combination trials. Methods: From 3/05 to 5/06 241 pts, including 13 with RCC, were randomized to P, 50 mg daily or 1200 mg weekly. Subsequently the protocol was amended to P, 100 mg daily or 900 mg weekly, and enrollment continues. Pts with measurable disease who received at least 2 courses of P and at least one tumor measurement after initiation of P were considered evaluable for response using RECIST criteria. After demonstrating P activity in RCC, two phase 1 studies of P combined with either sorafenib (SOR) or sunitinib (SUT) were initiated. In each study, the dose of P is escalated from 50 mg qd to 50 mg tid. SOR is escalated from 400 mg qd to 400 mg bid and SUT from 25 to 50 mg qd for 4 weeks out of 6. Results: In the broad phase II study, 6 pts (66%) achieved clinical benefit. (See table ) including 3 pts (33%) with partial responses [duration 4, 6.5 and 9 m] and 3 pts (33%) with SD [9+, 9+ and 10 m]. Three pts progressed. The main toxicities were grade 1 nausea, vomiting, diarrhea, and fatigue. Daily P was significantly better tolerated than weekly and data are presented in detail in another abstract. Enrollment in cohorts 1 and 2 of the P/SOR study is complete. No grade 3 or 4 toxicities and increase in hand foot syndrome has been seen. Accrual to cohort 1 of the P/SUT study is also complete. Enrollment will be complete by May 2007. Conclusions: P is active in RCC. Phase 1 trials of P with TKIs have demonstrated no increased toxicity with less than maximal doses of P and TKI [Table: see text] No significant financial relationships to disclose.
VEGF, PDGF alpha, PDGF beta, and C-Kit expression are not independent survival predictors in stage D2 prostate cancer (PC)
Authors: Kasimis B. , Chang V. T. , Hoover D. , Sikder M. , Gounder S. , Finch Cruz C. , Gonzalez M. L. , Cogswell J. , Srinivas S. , Blumenfrucht M. 
Published: March 2020

15623 Background: In PC, overexpression of VEGF, PDGF alpha, PDGF beta, and C-Kit has been reported in over 50% of biopsy samples and may be important predictors of survival. Methods: In an ongoing project, we reviewed the records of 26 patients (pts) with stage D2 PC and stained their archival tissue specimens for VEGF, PDGF alpha, PDGF beta, and C-Kit expression. Immunohistochemistry was performed at US LABS (Irvine CA). All immunostains were evaluated by two pathologists. Immunoreactivity was scored using a semiquantitative system for intensity of staining (0–3+) and % of tumor cells (0–3+). The total score was obtained by averaging the scores between the two readers. All pts had androgen deprivation and were followed at 3 months intervals with physical examination, CBC, chemistry profile and PSA levels. A stepwise Cox model was used with variables: Gleason score, Hemoglobin (Hgb), Alkaline Phosphatase (Alk Phos), PSA, LDH levels, and C-Kit positive or negative staining. Results: Median values were as follows: age 69 years (56–91), Alk Phos 139 U/L(60–1298), PSA 178 ng/ml (1.8–5677), LDH 169 IU/L (100–350), Hgb 12.8 gm/dl (6.8–16.3), Gleason score 8 (5–10), Survival 26 mos (8.3–144.1). The median value for C-Kit staining was 3 on a scale of 0–6. 18 pts were grouped into low staining group (0–4) and 8 pts in a high staining group (4.5–5). The Kappa Coefficient for C-Kit was 0.83, and ranged from 0.78–0.91 for the other 3 stains. In univariate survival analyses, C-Kit staining was a predictor for survival (p=0.037) but not PDGF alfa, PDGF beta, or VEGF. In the stepwise Cox model, independent survival predictors in order of significance were the Gleason score, Hgb, and PSA levels. Conclusions: In this sample, VEGF, PDGF alpha, PDGF beta, and C-Kit overexpression by immunohistochemistry in archival tissue are not independent predictors of survival. The C-Kit, however, has a small association with survival but may have collinearity with known predictors of survival. No significant financial relationships to disclose.
Phase II trial of paclitaxel in front-line therapy of hormone refractory metastatic prostate cancer
Authors: Kolevska T. , Goldstein D. , Davis C. , Fehrenbacher L. 
Published: March 2020

15628 Hormone refractory prostate cancer patients have poor prognosis with median survival of only 16 months. They are frequently elderly men with many co-morbid conditions unable to tolerate treatments with substantial toxicity. Docetaxel, the only drug shown to prolong survival causes significant toxicities, requires steroids administration, may cause poorly reversible neuropathy and requires long infusion times, all limiting its use in elderly men that are mostly affected by hormone refractory prostate cancer. Abraxane is a novel agent delivering paclitaxel without steroids, requires only 30 minutes infusion times and low toxicity potential that may be effective and more tolerable in patients with prostate cancer. The goal of our study is to evaluate the effectiveness and toxicity of Abraxane in first line chemotherapy of men with hormone refractory prostate cancer. Considering the favorable toxicity profile of Abraxane and in an effort to make our results applicable to the majority of prostate cancer patients we are including men with performance status of 2. Main eligibility criteria are: hormone refractory metastatic prostate cancer documented by PSA progression, no prior chemotherapy, PSA >5 and performance status 0–2. Primary endpoint is efficacy based on PSA response. Secondary endpoints are time to PSA progression, overall survival, and toxicities. The clinical trial has been opened at Kaiser Permanente Northern California since September 2005. There are 15 patients enrolled. All have been evaluable for toxicity and the drug is very well tolerated so far by this population of patients. Out of 15 patients 12 are evaluable for response. Two patients have recently started the protocol therapy and have not met the time point for disease assessment. One patient discontinued the treatment after one infusion due to toxicity (elevated LFTs). One patient completed 11 cycles of Abraxane, while maintaining stable disease on bone scan and achieved a PR by PSA. Ten patients have come off study due to progressive disease based on clinical presentation, rising PSA or signs of radiological progression. There are currently 4 patients actively receiving therapy. Updated results will be presented at the time of ASCO 2007 meeting. No significant financial relationships to disclose.