bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relation of tumor vascularity to effect of gemcitabine in pancreatic carcinomas: Value of contrast-enhanced harmonic ultrasonography
Authors: Kitano M. , Sakamoto H. , Suetomi Y. , Nishio T. , Nishio T. , Takeyama Y. , Kudo M. 
Published: March 2020

4114 Background: Most ductal adenocarcinomas of the pancreas are hypovascular as compared with the surrounding parenchyma on dynamic CT. Coded phase-inversion harmonic ultrasonography more clearly depicts fine vessels in pancreatic tumors after the infusion of ultrasound contrast than dynamic CT. In the present study, we observed the vascularity of pancreatic tumors by means of this technique and investigated its usefulness for evaluation of response to gemcitabine. Methods: Thirty-three patients with inoperable pancreatic carcinomas were enrolled in this study. They received gemcitabine (1 g/m2) 3 times in a cycle (4 weeks). Contrast-enhanced harmonic ultrasonography (CE-US) was performed immediately before the fist cycle and after completing each cycle, by the use of a GE LOGIQ 9 Series unit. We classified patients into 2 groups according to the changes of tumor vascularity observed by CE-US. Group A represents those with tumors in which tumor vascularity was increased during a certain period after the chemotherapy. Group B represents those with tumors in which tumor vascularity was not increased throughout the observation period. Tumor makers (serum CEA, CA19–9, Span-1 and Dupan-2) and median survival time (MST) were employed for the evaluation of therapeutic response and compared between the 2 groups. Results: CE-US demonstrated the increase of tumor vascularity after the chemotherapy in 17 of 33 patients (Group A). MST in the Group A (306 days) was significantly longer than that in the Group B (187 days). The reduction of tumor makers (reduction by 50 % of either serum CEA, CA19–9, Span-1 or Dupan-2) was observed in all patients (17/17) in the group A and in 25 % of patients (4/16) in the group B. The increase of tumor vascularity was noted when the tumor makers were reduced. The increased vascularity turned to decline in parallel with the tumor progression. Conclusion: CE-US is useful for the evaluation of chemotherapeutic response in terms of vascularity. The increased vascularity in pancreatic carcinomas after the chemotherapy may represent the improvement of vascular sclerosis and tumor invasion in small arterioles. No significant financial relationships to disclose.
A phase III trial of virulizin plus gemcitabine vs. gemcitabine alone in advanced pancreatic cancer: Results of subgroup analysis
Authors: Wright J. A. , Osterlee J. , Fekete S. , Lee Y. , Young A. H. 
Published: March 2020

4116 Background: Virulizin (V) is a novel antitumor immune modulator that improves survival in pancreatic cancer patients (pts) as monotherapy. A double-blind, multicenter, randomized, phase III study was conducted to evaluate the survival benefits and safety of V in combination with gemcitabine (G) in pts with advanced pancreatic cancer. Methods: Chemo-naive pts with locally advanced or metastatic pancreatic cancer with ECOG Performance Status (PS) of 0, 1 or 2 were enrolled. Pts were randomized to receive intramuscular injections of either V or placebo (P) 3 times weekly + G (1,000 mg/m2 weekly ×7 with 1 week rest, then weekly ×3 q4w). Randomization was stratified according to ECOG PS (0 or 1, and 2) and extent of disease (locally advanced and metastatic). Pts who showed no clinical benefit or were intolerant to G entered 2nd-line therapy (stage 3), in which pts continued to receive either V or P alone or with 5-FU, or best supportive care. The primary endpoint was survival, defined as time from baseline/treatment day 1 to time of death from any cause. Results: The intent to treat (ITT) population comprised 434 pts, of which 377 were efficacy evaluable (EE). Median overall survival for V + G was 6.3 months for the ITT population (6.8 months for EE pts) and 6 months for P + G for both ITT and EE pts. While differences in survival times were not statistically significant, exploratory analysis showed encouraging results in specific subgroups treated with V + G ( table ). Importantly, a significant difference was found in stage 3 pts who received V in a salvage setting compared to pts who received P. Conclusions: Pancreatic cancer pts with either low ECOG PS or metastatic cancer showed a survival benefit when treated with V + G, which was significant in pts who continued to receive V as a salvage therapy. Further studies in these targeted patient populations are being considered. [Table: see text] No significant financial relationships to disclose.
Gemcitabine hepatic arterial chemoembolization (TACE) in the treatment of unresectable HCC
Authors: Carr B. I. 
Published: March 2020

4141 Background: Hepatocellular carcinoma (HCC) generally arises in the presence of cirrhosis and is typically multifocal and bilobar and thus not often resectable. A major limitation of chemotherapy is due to the damaged underlying liver as a result of cirrhosis. A non-hepatotoxic drug such as Gemcitabine is thus potentially useful in patient management. Methods: 57 patients with biopsy-proven HCC were evaluated for response, survival and toxicity after treatment with gemcitabine via hepatic arterial chemoembolization. Patients were treated with 1250 mg/m2, given in 150 ml of normal saline over 30 min to either the right or left hepatic artery at any one treatment session. Treatments were repeated every 8 to 10 weeks. Embospheres (Embogold, Biosphere Medical) 100–300 micron size were also injected to vascular slowing but not to occlusion of the same hepatic artery during the chemotherapy infusion. A CT scan was performed at baseline and just prior to each repeat treatment, which was continued until tumor progression. CBC, liver function tests and AFP were performed at baseline and monthly. Results: There were 19 partial responses (PR) (33%), 2 minor responses (4%), 24 patients with stable tumors (42%), 9 with tumor progression (16%) and 3 unevaluable (diffuse) (5%). Survival was: median 12 mo (range 1–36 mo). 23 patients survived 24 mo. There were no hepatotoxicities greater than grade 1 and no myelotoxicities greater than grade 2 (NCI common toxicity criteria). Conclusions: Gemcitabine chemoembolization (TACE) in unresectable HCC patients with normal bilirubin and without ascites appears to be entirely safe with a minimal clinical or laboratory toxicity and is associated with encouraging responses and survival. No significant financial relationships to disclose.
Phase II study of lenalidomide in patients (pts) with metastatic renal cell cancer (MRCC)
Authors: Marsh L. , Khan M. , Needle M. , Amato R. 
Published: March 2020

4533 Background: Immunomodulatory drugs are compounds that originated via the deliberate structural modification of thalidomide. Lenalidomide (Revlimid) is a derivative with enhanced immunological and anti-angiogenic properties lacking toxicities associated with thalidomide. Objectives were to determine response rate, time to progression (TTP), one-year survival, and toxicity in patients with progressive MRCC. Methods: Eligibility included: progressive measurable MRCC, adequate organ/marrow function, zubrod performance status (ZPS) ≤ 2, ≤ 1 prior therapy, and no active CNS involvement. Lenalidomide is administered orally at a dose of 25mg daily for 21 days with 7 days rest (28-day cycle), with dose modifications for toxicity. Re-evaluation is done every 3 cycles (12 weeks). RECIST criteria is utilized to determine response rate. TTP is determined from entry into study. Results: 40 pts enrolled. 30 male/10 female, range 38–73 (median 63) years. 38 pts had clear cell carcinoma; 2 pts with papillary. 24 pts received prior immunotherapy and/or chemotherapy. 3 pts met criteria for good prognosis, 33 intermediate and 4 poor. Sites of disease included: lung, nodal, bone, adrenal, kidney, and liver. 17 pts had 1 metastatic site, 13 pts 2 metastatic sites, and 10 pts 3 or more metastatic sites. 36 pts completed at least 12 weeks of therapy. 4 pts had early progressive disease. 1 pt had a CR, 2 pts achieved a PR. 52% of pts had a prolonged TTP ≥ 6 months and 25% ≥ 12 months. Median overall survival of 14.8 months (4.1− 22.2+). Treatment related adverse events included: reversible grade 1/2 non-hematologic toxicity consisting of: nausea, diarrhea, constipation, myalgia and fatigue. 19 pts with grade 3/4 neutropenia and 9 pts with grade 3/4 thrombocytopenia. Median duration of therapy is 6 months (2 - 22). Conclusion: Lenalidomide was well tolerated. Anti-tumor activity has been demonstrated by the following: tumor regression and delayed TTP. The tumor effect was also demonstrated as a second line therapy following cytokine failure. [Table: see text]
Phase II study of lenalidomide in patients (pts.) with metastatic renal cell carcinoma (MRCC)
Authors: Choueiri T. K. , Dreicer R. , Rini B. I. , Elson P. , Garcia J. , Mekhail T. , Bukowski R. M. 
Published: March 2020

4539 Background: MRCC is a disease with susceptibility to immunomodulatory and anti-angiogenic approaches. Lenalidomide (LEN) is a structural and functional analogue of thalidomide with enhanced immunomodulatory properties and unique activity and toxicity profiles. A phase II study of LEN in MRCC was conducted to determine efficacy and safety. Methods: Eligibility included histologically confirmed MRCC, measurable disease, ≤ 1 prior systemic therapy, ECOG PS 0–1, adequate organ function, and no brain metastases. LEN was administered orally at 25 mg daily for the first 21 days of a 28-day cycle. The primary endpoint was objective response rate as determined by RECIST criteria. Patients received treatment until disease progression or unacceptable toxicity. A two-stage design was employed to test the null hypothesis that the true response rate is ≤ 5% versus the alternative hypothesis that the true response rate is ≥ 20% (alpha = 0.05, power = 90%). Results: 28 pts. were enrolled. Median age was 67 years (range, 42–76). All patients had prior nephrectomy and 57% (16/28) received prior therapy. 21 pts. (75%) had clear cell histology. Pts. received a median of 4 cycles of therapy (range, 1–12+) with 21 pts. (75%) completing at least 2 cycles. Three pts. (10.7%; 95% CI = 2.3–28.2 %) demonstrated a partial response (PR) and 8 pts (28.5%) had stable disease (SD). A total of 11 pts. (39%) experienced median tumor shrinkage of 5% (range, 1–72%). Median time to progression (TTP) for the entire cohort was 4 months (m) (range, 0.67–14+). Ten pts (36%) were progression-free for ≥ 6 m and five pts (18%) were progression-free for ≥ 12 m. Previously treated pts had a TTP of 3 m compared to 5 m for pts with no prior therapy (p = .19). 6 pts (21%) continue on-study with a median follow up of 12.6 m (range, 7.3–14.2 m). Toxicities (all grades) included fatigue (93%), skin toxicity (rash, dry skin and pruritus; 68%) and leukopenia/neutropenia (65%). Grade 3/4 toxicities included fatigue/constitutional symptoms (11%), skin toxicity (7%) and leukopenia/neutropenia (29%). Conclusions: LEN demonstrated an anti-tumor effect in MRCC as evidenced by partial responses and additional pts. with tumor shrinkage. LEN was well tolerated with manageable toxicity. Further studies are warranted. [Table: see text]
Phase II screening study to assess the combination of a LHRH analogue, dexamethasone and a somatostatin analogue versus a LHRH analogue with dexamethasone in hormone refractory prostate cancer patients
Authors: Silva F. , Calais Da Silva F. M. , Gonçalves F. , Oliver T. 
Published: March 2020

4565 Background: Hormonal changes and the possible resulting imbalance between androgen and estrogen levels in elderly men may play an important role in prostatic pathogenesis. Androgen suppression can induce regression of prostatic carcinoma. Ample laboratory and clinical research have contributed to evidence that a direct link exists between prostatic cell growth, prostatic carcinoma cell growth and hormones, mainly testicular androgens. As far as prostatic cancer is concerned, we know that SMS blocks GH, PRL, tissular growth factors (TGF) and that it has a direct antiproliferative growth cellular growth effect. The simultaneous administration of depot forms of SMS and LHRH analogues induced the greatest decrease in tumor growth. Methods: A randomized 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 somatulin (120 mg every 4 weeks), with respect to PSA response rate, time to PSA progression, duration of survival and toxicity. Results: 72 patients with a median time PSA of 77 ng/ml were randomized by 3 institutions, 35 to decapeptyl, dexamethasone and somatulin (DDS) and 37 to decapeptyl and dexamethasone (DD). 21 of 33 (64%) patients on DDS and 21 of 32 on DD (66%) had a PSA response (a decrease of at least 50 % as compared to baseline). The median duration of PSA response was 6.6 months on DDS and 3.4 months on DD. Overall, the median time to PSA progression was 5.8 months on DDS and 1.8 months on DD. The median duration of survival has not yet been reached. Both treatment regimens were well tolerated. The most frequent toxicities on DDS and DD were hot flushes (27%, 10%), gastrointestinal (18%, 20%), and skin complaints (12%, 10%). Conclusions: Both treatment regimens are active and safe in the treatment of hormone refractory prostate cancer. Although the PSA response rate is about 65%, the median duration of response and median time to progression were longer in the somatulin arm; so, the data suggest a possible advantage of DDS with respect to both the duration of the PSA response and the time to PSA progression. Further follow-up is required to assess survival. No significant financial relationships to disclose.
Long term efficacy of peripheral androgen blockade on prostate cancer: CALGB 9782
Authors: Picus J. , Halabi S. , Small E. , Hussain A. , Philips G. , Kaplan E. , Vogelzang N. 
Published: March 2020

4573 Background: The treatment of patients with a rising PSA after definitive local therapy is controversial. Patients are reluctant to undergo androgen suppression due to side effects and interest focuses on the timing and intensity of additional therapy. The use of peripheral androgen blockade in this setting is appealing. Methods: Patients with a rising PSA after definitive local therapy were enrolled in a multi-institutional trial. Accrual of 101 patients lasted from Sept 30, 1998 to July 16, 2001. All patients had undergone previous definitive local therapy at least 1 year, and no more than 10 years prior to enrollment. All patients had a repeated rising PSA, above 1 ng/ml, with no detectable evidence of recurrent disease. CT and bone scans were negative. Patients received a combination of oral therapy consisting of Finasteride, at a dose of 5 mg/day, and Flutamide, at a dose of 250 mg TID. Results: The median age was 71, with a median baseline testosterone level of 322 ng/dl. A >80% PSA decline was seen in 91/94, (97%) of the patients. Three other patients had PSA declines of 77%, 73% and 38%, all of which were maintained for at least 28 days. The median time to PSA nadir was 3.2 months. The current median follow-up is 59 months. To date, only 22 patients have progressed, with 47 patients still on peripheral androgen blockade. Eight patients have died without progression, and 22 patients went off therapy for other reasons not related to progression. Also noted were patients showing PSA responses to Flutamide withdrawal, and per protocol remaining on Finasteride. Toxicity to date remains very mild. Conclusions: Peripheral androgen blockade showed excellent activity produced durable PSA responses in this select group of patients. While the clinical significance of a decline in PSA alone is not fully understood_the durability of these PSA responses is encouraging. The median duration of progression free survival and overall survival has not been reached, and is likely to be longer than five years. Quality of life data is undergoing further analysis. This report supports further study of less aggressive treatments for patients who have only a rising PSA after definitive local therapy. No significant financial relationships to disclose.
Phase II study of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial carcinoma (UC): Analysis of the second cohort of CALGB 90102
Authors: Philips G. , Sanford B. , Halabi S. , Bajorin D. , Small E. J. 
Published: March 2020

4578 Background: The epidermal growth factor receptor (EGFR) is frequently expressed in UC and carries a poor prognosis. C has preclinical synergy with gefitinib and GC plus gefitinib was safe in lung cancer patients (pts). In a UC trial of GC using fixed dose rate infusion of G plus gefitinib, Gr 4 and 5 toxicities led to premature closure of the study after 27 patients. Because toxicity was felt to be related to the fixed dose rate infusion of G, accrual was resumed with a standard G dosing schedule in a second cohort. Methods: Eligible pts had measurable N2, N3 or M1 disease; PS of 0–2; CrCl of > 50 ml/min; adequate organ function; no prior systemic combination chemotherapy. Treatment consisted of C 70 mg/m2 D1, G 1000 mg/m2 D1+8 given over 30 min every 3 weeks concurrent with gefitinib 500 mg/day PO for a maximum of 6 cycles. Responders received maintenance gefitinib 500 mg/day until progression. Results: In 55 eligible pts with a median age of 64 years, 67% (of 49) had visceral metastases and 91% had PS of 0–1. Objective response (CR+PR) was observed in 51% (95% CI = 37–65). With a median follow up of 13.2 mo, the median time to progression was 8 mo (95% CI = 6.8–9.2) on the basis of 45 events, and the median overall survival was 14.4 mo (95% CI = 10.7–20.9) on the basis of 26 deaths. No lethal toxicity was seen. Gr 4 toxicities included Gr 4 neutropenia (20%) and Gr 4 metabolic/electrolyte disorders in 13%. Gr 3 and 4 diarrhea was observed in 25% and 2 % of pts respectively and Gr 3 skin rash in 16% of pts. Conclusions: The combination of GC and gefitinib has acceptable toxicity in advanced UC. However, the relative contribution of gefitinib to the efficacy of this regimen remains uncertain. These preliminary results do not suggest a substantial improvement upon historical results with GC alone in advanced UC. No significant financial relationships to disclose.
Prognostic significance of the level of serum osteoprotegerin in patients with bladder cancer
Authors: Mizutani Y. , Li Y. N. , Shiraishi T. , Nakamura T. , Nomoto T. , Okihara K. , Ukimura O. , Yoneda K. , Kawauchi A. , Miki T. 
Published: March 2020

4581 Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an important role in cytotoxic T lymphocyte-mediated and natural killer cell-mediated apoptosis against cancer cells. Since Osteoprotegerin (OPG) is a soluble decoy receptor for TRAIL, circulating OPG has been implicated in protection from TRAIL-mediated apoptosis. This possibility was examined in patients with bladder cancer. Methods: Serum OPG levels of 185 patients with bladder cancer were determined by using an enzyme-linked immunosorbent assay. Anti-autologous tumor cytotoxic activity of peripheral blood lymphocytes was assessed by the 12-h Cr release assay. Results: The mean serum OPG level in patients with bladder cancer was approximately 3-fold higher than that in normal donors. The serum OPG level in patients with muscle-invasive bladder cancer was higher than that in superficial bladder cancer. Furthermore, serum level of OPG in patients with metastatic bladder cancer was higher than that in muscle-invasive bladder cancer. Serum OPG level in Grade 2 bladder cancer was higher than that in Grade 1 cancer. Moreover, serum OPG level in Grade 3 bladder cancer was higher than that in Grade 2 cancer. Patients with superficial bladder cancer with low serum OPG level had a longer postoperative tumor-free rate than those with high level in the 5-year follow-up. In addition, patients with muscle-invasive bladder cancer with low serum OPG level had a higher disease-specific survival rate when compared with patients with high level in the 5-year follow-up. There was an inverse correlation between serum OPG level and anti-autologous tumor cytotoxic activity. Conclusions: The present study is the first to demonstrate that the serum OPG level correlates with the stage/grade of bladder cancer, and that elevated level serum OPG predicted early recurrence in patient with bladder cancer. These findings suggest that serum OPG level may be used as a prognostic parameter in patients with bladder cancer, and that OPG may be a molecular therapeutic target in bladder cancer. No significant financial relationships to disclose.
Multicenter, randomized, phase III trial comparing radical retropubic prostatectomy with conventional external beam radiotherapy for localized prostate cancer: An interim report
Authors: Di Stasi S. M. , Giannantoni A. , Valenti M. , Storti L. , Attisani F. , Palloni T. , Jannini E. A. , Bibas M. , Zampa G. 
Published: March 2020

4607 Background: We report the outcomes of a randomised trial comparing radical retropubic prostatectomy (RP) with conventional external beam radiotherapy (EBRT) in patients with clinically localized prostate cancer. Methods: Between January 1997 and September 2001, 137 patients with clinically localized diagnosed prostate cancer were randomly assigned to RP (n = 70) or EBRT (n = 67). Data collected at follow-up included evidence of clinical disease progression, survival rates and general and disease specific health-related quality of life. All data were measured by physical examination, digital rectal examination, PSA, annual TC and bone scan and questionnaire. Analysis was by intention to treat. Results: After a median follow-up of 67 months (range 24–88) 35 patients (32.8%) had evidence of biochemical disease progression, 22 (31.4%) in RP group and 23 (32.8%) in EBRT group respectively. The median time to biochemical failure was 55.5 months (range 1–86) in RP group and 56 (range 3–88) in EBRT group. A local progression was observed in 11 patients (15.79%) of RP group and 12 (17.9%) of EBRT group. The median time to local progression was 65 months (range 6–86) in RP group and 64 (range 6–88) in EBRT group. Distant metastases were observed in 4 patients (5.7%) in RP group and 6 (8.9%) in EBRT group. The median time to distant failure was 67 months (range 12–86) in RP group and 66 (range 12–88) in EBRT group. Death due to prostate cancer occurred in 3/70 of patients assigned to RP (4.3%) and in 1/67 of those assigned to EBRT (1.5%). A significant decrease in general HRQOL was evident only in the first month after RP (p < 0.001). At 2 years, patients undergoing RP report significantly worse urinary function (p < 0.001), but better bowel function than those treated with EBRT (p < 0.001). Sexual dysfunction was more prevalent in the RP than in the EBRT group (70.2% versus 61.2%). Conclusions: This interim analysis indicates that there was no significant difference between RP and EBRT in terms of clinical disease progression and survival rates in patients with clinically localized prostate cancer. However, additional larger sample size accrual and long-term follow-up data are warranted to confirm these results. No significant financial relationships to disclose.