bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fixed infusion rate (FIR) gemcitabine (G) based treatment for advanced renal cell carcinoma (ARCC): Efficacy and toxicity data from a phase II study
Authors: Zustovich F. , Cartei G. , Ceravolo R. , Salmaso F. , Zovato S. , Artioli G. , Cingarlini S. , Binato S. , Pastorelli D. 
Published: March 2020

14632 Background: ARCC is still an untreatable disease because high dose IL2 therapy is feasible and effective only in a small percentage of patients (pts). Standard dose IL2 is palliative as well as every other treatment. G is a well tolerated agent, even in aged pts and is moderately effective in ARCC. FIR of 10 mg/m2/min increases intracellular G active metabolites and may enhance therapeutic and toxic effect. Aim of study was to evaluate the FIR-G effectiveness in ARCC. Methods: G was administered IV at 10 mg/m2/min FIR for 50 to 1250 min according to age and PS on day 1,8,15 every 28. Immunotherapy (IT) was IL2 3MU subcutaneously daily for 5 days a week or Alfa-INF 3MU three days a week, chronically given. Results: We enrolled 23 pts; 5 female; median age 59 years (29–75), all stage IV disease, all nephrectomized with histologically confirmed clear cell carcinoma; median Fhurman’s grade was 3 (1–4); median PS was 2 (0–3); 9 pts had bone mets; prior treatments: IT, mostly low doses IL2, in 12 pts; chemotherapy in 7 pts and palliative radiotherapy in 9 pts. 125 cycles (median of 5, range 1–35) were administered with a median G dose of 1050 mg/m2 over 105’. 13 Pts received IT (11 pts were IT naïve and received IL2 and 2 pts previously treated with IL2 received Alfa-INF). In the 22 pts valuable for toxicity grade 1–2/#pts was: granulocytopenia/5, anemia/2, nausea/5, vomiting/2, constipation/1, mucositis/1, fever/1, infection/1, fatigue/2, cutaneous/5, peripheral edema/4; grade 3–4 was: anemia/3, nausea/1, fatigue/3, cutaneous/1, vascular venous/1, peripheral edema/1. 26 cycles had to be delayed due to side effects. In the 22 valuable pts we reported 3 PR with a RR of 14% and 11 pts (50%) had SD. All pts were valuable for TTP with a median of 5.6 months (1–35). Data on OS are still immature with a median of 15+ (3–55+). Conclusions: FIR-G ± IT is safe and moderately effective against ARCC. Due to the small number of pts no separate analysis is possible between G ± IT or prognostic factors groups. Nevertheless our TTP and OS data are promising considering the detrimental prognostic factors in the treated population. Present work was part of studies program of, and partly supported by, AOI (Associazione Oncologia Italiana), Padova, Italy. No significant financial relationships to disclose.
Oral bisphosphonates fail to prevent bone loss from androgen deprivation therapy in men with prostate cancer
Authors: Lam R. Y. , Scholz M. , Guess B. , Trilling T. 
Published: March 2020

14643 Background: Androgen deprivation therapy (ADT) is a widely administered treatment for prostate cancer. However, ADT is associated with accelerated bone loss, osteoporosis, and fractures (Shahinian, NEJM 2005; 352:154). According to Smith et al, annual bone loss on ADT approaches 9% (Smith, NEJM 2001;345:948), using QCT densitometry, a highly sensitive test for the detection of osteoporosis in men. Intravenous bisphosphonates (pamidronate, zolendronate) have been shown to prevent ADT-related bone loss in randomized phase III trials. We performed a retrospective analysis to determine if oral bisphosphonates effectively prevent bone loss in men receiving ADT. Methods: Twenty two men, ages 60–80, were placed on alendronate or risendronate at the initiation of ADT. Baseline and follow-up bone mineral densitometry (BMD) studies were performed with QCT densitometry. Repeat BMD was performed 12- 27 months (mean = 17mo) after the baseline BMD. Percentage change in bone density was annualized. Within each treatment group, the hypothesis of no mean change from baseline was analyzed using a paired t test. Results: Mean baseline bone density was 122.6mg/cc. Mean follow-up bone density was 112.7mg/cc. For the whole group, the annualized mean change in BMD was negative 7.77%/yr (p = 0.0003). Of note, 9/22 men maintained or gained bone density (-1.26% to +5.95%). 13/22 men lost at least 6.03% (-6.03% to -23.2%). There was no unexpected toxicity or fractures. Conclusions: In this retrospective study, prophylactic oral bisphosphonates do not protect against accelerated ADT-induced bone loss in men with prostate cancer. No significant financial relationships to disclose.
Talactoferrin alfa is an anti-cancer agent with activity in renal cell cancer (RCC) patients and a novel immunomodulatory mechanism of action
Authors: Varadhachary A. , Spadaro M. , Engelmayer J. , Blezinger P. , Valli T. , Petrak K. , Pericle F. , Mokyr M. B. , Forni G. , Hayes T. G. 
Published: March 2020

14648 Background: Talactoferrin alfa (talactoferrin) is a novel, orally administered immunomodulatory protein with demonstrated anti-cancer activity in preclinical experiments. Methods: Talactoferrin’s safety and efficacy in cancer patients was evaluated in a Phase I/II trial. Patients with metastatic disease who had failed standard therapy were treated with single-agent oral talactoferrin. Tumors were measured by CT scan using RECIST criteria. Talactoferrin’s mechanism of action was evaluated in preclinical experiments in tumor-bearing immunocompetent BALB/c and knockout mice. Cytokine levels were measured by ELISA. Cellular changes were measured by FACS analysis and immunofluorescence. Results: Seven patients with metastatic RCC who had failed previous systemic therapy were treated with oral, single-agent talactoferrin. Talactoferrin was safe and very well tolerated without a single drug-related SAE. All seven patients achieved at least Stable Disease, with one patient showing a deep and sustained partial response (71% shrinkage by RECIST two years after start of therapy). There was an apparent increase in median PFS to 7.3 months, with two patients still progression free after two years. Median OS has not yet been reached. In experiments conducted to define its anti-cancer mechanism, orally administered talactoferrin was found to act at the gut and the Gut Associated Lymphoid Tissue (GALT). Talactoferrin induced the chemotaxis of immune cells to intestinal Peyer’s Patches in mice, initiating an immunostimulatory cascade in the GALT and activating both innate and adaptive immunity. We observed significantly increased numbers of Dendritic Cells, NK-T cells and CD8+ T-lymphocytes in small intestinal Peyer’s patches, a systemic increase in Natural Killer (NK) and Cytotoxic T-lymphocyte (CTL) activity, activation of tumor draining lymph nodes, and cellular infiltration of distant tumors. The critical role of NK-T and CD8+ cells was demonstrated in knockout and depletion experiments. Conclusions: Talactoferrin, a first-in-class molecule with apparent clinical anti-cancer activity in RCC, acts through a novel immunomodulatory mechanism of action. [Table: see text]
Genetically altered Salmonella typhimurium profoundly increases survival in nude mice with metastatic PC-3 prostate tumors
Authors: Hoffman R. M. , Zhao M. , Geller J. , Yang M. , Ma H. , Tan X. , Li X. 
Published: March 2020

14653 Background: We previously published that a genetically-altered Salmonella typhimurium, expressing GFP, could completely destroy subcutaneously-implanted PC-3 tumors in nude mice when injected locally or intravenously (PNAS 102, 755–60, 2005). The bacteria are leu-arg auxotrophs which enable the bacteria to grow in PC-3 tumors but not in normal tissue. Methods: In the current study, we explore the effect of this bacteria, termed S. typhimurium A1, on metastatic PC-3 tumors orthotopically implanted in nude mice. PC-3 is a non-hormone-dependent prostate cancer. In this study, 20 mice were implanted orthotopically with PC-3 tumors expressing GFP. Approximately 2 weeks following implantation, the tumors were externally imageable. Ten of the 20 mice served as controls and followed until death without treatment. Ten mice were given the S. typhimurium A1 weekly intravenously, beginning at 2 weeks when the tumor GFP was first externally visible, and survival time was compared to the untreated mice. Ten additional non-tumor-bearing mice served as controls for the possible toxicity of S. typhimurium A1 and were also injected weekly with the bacteria intravenously. Results: Of the 10 mice with the PC-3 tumors injected weekly with S. typhimurium A1, 7 were alive and well at the time the last untreated mouse died. Currently, 4 treated mice remain alive and well 17 weeks following implantation. 3 of these 4 mice had no external fluorescence for the past 5 weeks despite discontinuing S. typhimurium A1. One mouse shows a progressive decrease in fluorescence, only a tiny spot if left. This mouse continues on S. typhimurium injection weekly. Conclusions: Injection of genetically-altered leu-arg-auxotrophic S. typhimurium into mice with metastatic PC-3 tumors has resulted in more than the tripling of lifespan of 4 of the mice. Three of the mice appear “cured” and have not external fluorescence despite discontinuing S. typhimurium treatment for the past 5 weeks. One mouse continues on weekly injections of S. typhimurium and is well with decreasing fluorescence. Since human prostate cancer eventually becomes non-androgen-dependent similar to PC-3 tumors, genetically-altered bacteria represent a novel potential treatment for this disease. No significant financial relationships to disclose.
Chemotherapy with a combination of consecutive low-dose cisplatin with ifosfamide and epirubicin (CLD-IEP) in sarcoma uteri
Authors: Shimizu Y. , Katase K. , Ishiya T. , Takahashi Y. , Yamada M. , Umezawa S. , Utsugi K. 
Published: March 2020

15016 Background: To evaluate the efficacy and toxicity of CLD-IEP for patients (pts) with sarcoma uteri. Methods: Eligible criteria were: a histologic proof of advanced or recurrent sarcoma uteri; measurable lesions; age between 18 and 75 yrs; WHO PS 0–3; WBC ≥ 3,000/μL; platelet count ≥ 100,000/μL; hemoglobin level ≥ 9 g/dL; adequate liver function; C-Cr ≥ 40 mL/min; no lung, heart, or brain disease; no previous neoplastic disease; no prior chemotherapy; and informed consent. The CLD-IEP regimen was ifosfamide 700 mg/m2 infused over 2 hrs days 1 through 4; epirubicin 50 mg/m2 bolus day 7; and cisplatin 15 mg/m2 infused over 2 hrs days 1 through 5. The treatment was repeated at 4-week intervals. Results: To date, thirty-eight eligible pts (17 leiomyosarcoma [LMS], 4 endometrial stromal sarcoma, and 17 carcinosarcoma) were enrolled in this study and all pts were assessable for response, toxicity, and survival. The median age was 53 yrs (range, 37–77). Twelve pts received CLD-IEP in the neoadjuvant setting. Nine pts had prior radiotherapy. After a median of 4 cycles (range, 2–13), we observed objective responses in 22 pts (58%), with 5 (13%) CRs and 17 (45%) PRs (95% CI, 40% to 76%, 4% to 22%, 27% to 63%, respectively). Of 17 pts with LMS, 1 CR and 7 PRs (1 pt with good PR surviving more than 48 months after the start of CLD-IEP) were observed. Median overall survival time (MOS) after the start of CLD-IEP for all 38 pts was 17.5 months (range, 2.7 to 61.5). MOS was 20.8 months in the responders versus 9.9 months in the non-responders (Log-rank, p = 0.023). The median progression-free survival time of the responders was 10.5 months. NCI-CTC grade 3 or 4 leucopoenia, neutropenia, thrombocytopenia, and anemia occurred in 63%, 75%, 12%, and 18%, respectively. There was no significant nausea/vomiting, nephrotoxicity, or CNS toxicity. Conclusion: CLD-IEP regimen has significant to moderate anti-tumor activity with acceptable toxicity in pts with sarcoma uteri including LMS. No significant financial relationships to disclose.
Residual tumor status in clinical trials of advanced ovarian cancer: A systematic review
Authors: Beltrán M. , Hernández X. , Abal C. , Velasco M. , Rubio J. , Colomer R. 
Published: March 2020

15024 Background: To determine whether the proportion of optimal disease status after surgery has changed along a defined period (the platinum era) on the setting of randomized clinical trials (RCT) in advanced ovarian cancer ( AOC). Methods: All RCT of chemotherapy for AOC in the platinum era (accrual period from 1980 to 2002) were searched. Studies were identified in an intensive review in MEDLINE, EMBASE and Cochrane Database, plus bibliographic references in the articles. We included those studies reporting stage, residual disease status and accruing both optimal and suboptimal disease. Simple linear regression models (slrm) were generated to evaluate the proportion of optimal disease status and of FIGO stages over time. Results are reported as two-side p values and 95% confidence intervals. Results: Seventy-five randomized studies, including 20,981 patients, fulfilled the inclusion criteria. Forty-two % of cases had optimal disease after surgery. Stage distribution was as follows: stage I-II, 7.5%, stage III, 72%, stage IV, 20%. Optimal disease status after surgery increased steadily over time, with larger proportions in more recent studies (r=.55; p < .005). Although there was a significant increase in stage I-II cases (r=.41; p < .005), inclusion of patients with stage III and stage IV did not change over time. Conclusions: Reported randomized clinical trials of chemotherapy for advanced ovarian cancer from 1980 to 2002 show a significant trend towards better postsurgical status of residual disease, with a larger proportion of patients with optimal disease in the more recent trials. This is marginally influenced by FIGO stage and therefore, occurs more likely from more extensive surgical debulking procedures. These changes in surgical approach result in an improvement of outcome, that may be independent of the postsurgical treatment used. No significant financial relationships to disclose.
Early evaluation of response to neoadjuvant chemotherapy in stage IIIC-IV epithelial ovarian cancer patients by 18FDG-PET and CA 125: Preliminary findings from the Arianna Project 02
Authors: Cacciari N. , Fanti S. , Zamagni C. , Rosati M. , Massari F. , Musto A. , Rosati F. , De Iaco P. , Melotti B. , Martoni A. 
Published: March 2020

15039 Background: Early evaluation of response to primary chemotherapy (PSC) in epithelial ovarian cancer (EOC) pts could allow to administer a proper number of cycles in order to obtain optimal results. Arianna Project 02 is aimed to investigate early tumor response to PSC correlating a set of routine and experimental hystological, biological and gene-expression profile data with clinical data before, during and after PSC. Methods: Stage III-IV EOC received 6 cycles of carboplatin AUC 5 and paclitaxel 175 mg/m2 and are evaluated at baseline and before each cycle by 18FDG-PET, CA 125, circulating tumor cells and experimental circulating bio-markers. Ultrasounds, CT scan and pelvic MRI are done at baseline and every other cycle. This preliminary report is focused on the correlation between changes of PET and CA 125 serum levels and pathological response. Results: Up to now 6 out of 11 pts completed PSC and surgery. Baseline tumoral 18FDG uptake expressed as Standardized Uptake Value (SUV) and CA125 were abnormal in all pts (SUVmax range: 12.1–20; CA 125 range: 416–2026 U/ml, upper normal limit 35 U/ml). One complete and 4 partial pathological remissions > 90% and one no change were observed. Mean (with range) SUVmax and CA125 decrease (Δ SUV and Δ CA125) measured after the 1st, 2nd, 3rd and last cycle of PSC in the 5 responders are similar (table). In the non-responder SUV decreased by 63% after the 1st cycle of PSC, but increased to baseline value after the 2nd cycle and remained unchanged until surgery, while CA 125 progressively decreased from 416 U/ml to 47 U/ml. Conclusions: These preliminary findings indicate that the behaviour of PET and CA 125 in responders are similar. More data are necessary to define the role of PET in the early evaluation of response to PSC in EOC pts. The study is still ongoing and the relationship between evaluation performed by PET and CA125 and by CT scan, ultrasound and pelvic MRI will be presented at ASCO meeting. [Table: see text] No significant financial relationships to disclose.
Is there a CA-125 level that predicts negative second look surgery (SLS) in patients with advanced epithelail ovarian cancer (EOC)?
Authors: Sharma S. , Singhal P. , Odunsi K. , Lele S. 
Published: March 2020

15042 Background: The value of second look surgery (SLS) in advanced epithelial ovarian cancer (EOC) has been has been questioned because performing this procedure has not been associated with a clear survival advantage.However, SLS continues to be the most accurate means of documenting the response to chemotherapy, and therfore still used in investigational protocols. The primary purpose of this study was to assess the levels of CA 125 after treatment, that could predict absence of disease at SLS. Methods: Between 1998 and 2003, 98 stage III EOC patients who underwent optimal cytoreductive surgery, completed 6 cycles of platinum/paclitaxel chemotherapy, and were NED (no evidence of disease: normal CA 125, normal physical and radiological examination) were included in this study. SLS was performed at 6–8 weeks from completion of primary therapy. Patients with disease present at SLS were considered to have persistent disease and received second line chemotherapy. Patient demographics, surgical and chemotherapy treatments, and CA 125 levels prior to start and at completion of primary treatment were collected retrospectively. Survival was estimated by the Kaplan-Meier method. Results: Forty seven out of 98 (48%) of optimally debulked patients who were NED at completion of primary therapy underwent SLS. Twenty-five out of 47 patients (53%) had evidence of disease at SLS and 22 out of 47 patients (47%) were NED at SLS. The median disease free survival was 42 months (95% CI 16, 81) in patients with negative SLS compared with 17 months (95% CI 9, 45) in patients who did not undergo SLS (p = 0.03). Estimated 5-year survival in patients with negative SLS was 90% compared to 50% in patients who did not undergo SLS (p = 0.05). CA 125 levels of ≤ 10 after completion of primary therapy was predictive of negative SLS (p < 0.05). Conclusions: SLS evaluation of disease status appears to be a more accurate than standard clinical evaluation in patients who are NED at completion of their primary therapy. Negative SLS also appears to be a predictor of improved disease free and overall survival. Furthermore, CA 125 ≤ 10 is predictive of negative SLS in patients who are NED after completion of primary therapy. No significant financial relationships to disclose.
Maintenance therapy in epithelial ovarian cancer (EOC): Could EGFR inhibitor- gefitinib be a candidate drug? A pilot study
Authors: Hariprasad R. , Kumar L. , Patnaik R. , Gupta A. , Kumar S. 
Published: March 2020

15046 Background: We aimed to evaluate the role of EGFR inhibitor, gefitinib among patients with advanced & recurrent EOC to prolong progression-free survival (PFS). Methods: Between Nov. 2004 and Dec. 2005, 32 patients (median age 45 years, range 33 to 63) have been recruited. The study subjects were - (i) eleven patients with EOC stage IIIC-IV who had gross residual disease (≥1 cm) after primary debulking surgery and had achieved complete response (CR) following six cycles of paclitaxel and carboplatin (Group-I) (ii) Group II - includes 21 patients who achieved CR following salvage chemotherapy for relapsed EOC (1st relapse- 8, 2nd- 8, 3rd -3 & 4th relapse in 2 patients). All Patients received gefitinib 250 mg once daily till evidence of relapse. Patients were examined every month and toxicity (CTC version II) was recorded. Serum CA-125 was done once in 2 months and CAT scan of abdomen & pelvis at 6 monthly interval. The study was approved by Institute Ethics Committee and informed written consent was obtained from each patient before starting Gefitinib. Results: The mean duration of treatment is -5.6 months (Gp-I: 7.7 months, Gp-II: 4.5 months). Toxicity was mild, mainly in the form of skin rash & diarrhoea. Skin rash occurred in 10 patients (31.3%); Group I - 8 patients (grade IV-2, III-2, I-4) & in 2 patients in group II (grade III-1, II-1). Diarrhoea occurred in 7 patients (22%); Group I-1, group II-6) all grade I. No pulmonary or hematological toxicity was observed. Currently, 18/32 patients are on Gefitinib (mean duration of treatment 6.1 months); in 12 patients gefitinib has been discontinued due to relapse (group I- 4, Group II-10). Among 10 patients with skin toxicity (Gp I-8, Gp II-2), 6 continue to be disease-free (Group I- 5, Group II-1) compared to 12 of 22 without skin toxicity. Conclusions: Toxicity to gefitinib was mild, and limited to skin and GIT. Correlation between EGFR expression vs. response can help in identifying patients who possibly might benefit with gefitinib therapy. No significant financial relationships to disclose.
Efficacy of pegylated liposomal doxorubicin (PLD) and oxaliplatin (OX) in pre-treated advanced epithelial ovarian cancer (EOC) and relation to p53 status
Authors: Nicoletto M. O. , Donach M. E. , Borgato L. , Angelini F. , Artioli G. , Azzoni P. , Perin A. , Barile C. , Bertorelle R. , Cecchetto A. , Cartei G. 
Published: March 2020

15054 Background: The efficacy of PLD+Ox in pre-treated advanced EOC in third and fourth line suggests that the elevated survival in these patients might activate the p53 pathway. Methods: Inclusion criteria: Performance Status≤2, relapse or progression after 1–3 lines of therapy; ≤4 prior antiblastic drugs; life expectancy >3 months; LVEF >50%.Treatment consisted of 1 hr infusion of PLD 30–35 mg/m2 on day 1 and 70 mg/m2 of Ox in 2 hrs on day 2 for 8 cycles, then 2 cycles of PLD alone. Clinical response was evaluated by CT scan every 3 cycles. Primary endpoints were overall survival and its correlation with p53. Results: From June 2000, 65 pre-treated pts were enrolled. They were divided according to platinum sensitivity into sens, part-sens and res (time to progression after platinum therapy of ≥12, ≥6 or <6 months). Median age = 65 yrs, range 41–84, (23 pts >70 yrs). 56 pts were evaluable for response: 28 sens with an ORR = 79%, 15 part-sens ORR = 47%, and 12 res ORR = 50%. 445 cycles were administered (median = 6 cycles/pt). Median survival from 1st cycle was 19 months, 10 and 8 months in sens and part-sens and res groups respectively (p = 0.00021). Major (G3–4) toxicities were: neutropenia (6 episodes), gastrointestinal (3 episodes). G1–2 neurosensorial toxicity was seen in 18 pts and PPE in 10 pts. 1 toxic-related death was recorded. Median LVEF showed no significant changes during treatment. There is no clear correlation between OS and amount of Platinum/Taxol administered previously. p53 was analyzed for expression and mutations. Mutations were sought in exons 5, 6, 7 and 8. Immunohistochemistry of 11 amplified samples showed p53 overexpression in 8 pts, of these 7/11 had a CR and/or PR (64%). The analysis is ongoing. The 5-yr survival after first relapse is 64%, 24% and 0% for sens, part-sens and res respectively. 6/6 (100%) evaluable patients with BRCA mutations responded to therapy (5 BRCA1 pts, 1 BRCA2 pt): 4 CR and 2 PR, presently all living. Conclusions: The therapy is effective in increasing OS in Platinum-sensitive patients after re-exposure to Carboplatin and Taxol and may be effective in p53+/mutated pts and for pts with BRCA mutation. For Pt-refractory and Pt-partially-sensitive pts an optimized use of this treatment must be identified. No significant financial relationships to disclose.