bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of angiogenis activation during interleukin-2 infusion in patients with renal cell cancer (RCC)
Authors: Simonelli C. , Talamini R. , Bearz A. , Berretta M. , Monini P. , Sgadari C. , Sartor I. , Ensoli B. , Vaccher E. , Tirelli U. 
Published: March 2020

14640 It is well known that during IL-2 administration a complex activation of the cytokine network is on going, but few data are available about the effect of this activation on angiogenesis. In our Institution all patients with metastatic RCC undergo to the following schedule of IL-2 infusion: IL-2 10 MIU continuous infusion (ci) 5/7 days, one week off followed by IL-2 10 MIU ci 5/7 days, 4 week off (1 cycle); for a total number of 2 cycles. We evaluated the activation of angiogenesis measuring the plasma level of VEGF MMP2 and MMP9 before, during and after the 5 days IL-2 ci. In 13 patients analysed, before IL-2 ci, we have the following median level of plasma VEGF (773+ 378 pg/ml), MMP2 (55.9 + 19.9 ng/ml) and MMP9 (1146+498 ng/ml). The baseline median values of VEGF MMP-9 showed a trend to correlate with the number of metastasis before therapy. During 3 days of IL-2 ci we did not observed any significant increase of VEGF MMP2 and MMP9 as well as after 24 hours from the end of the 5 days ci. On the contrary, at the same time-points, during and after IL-2 ci, we observed the activation of pro-inflammatory cytokines network, measured by the statistically significant increased levels of neopterin IFN-γ and TNF-α and sIcam.This preliminary observation demonstrated that IL-2 ci, even if it highly activates the release of pro-inflammatory factors, does not affect the release of angiogenic surrogate markers such as VEGF MMP2 and MMP9. On the basis of our experience we can suggest that the most suitable time to test angiogenesis inhibitors during IL-2 therapy appear to be the intervals between IL-2 administration and not during IL-2 infusion when the most severe side effects occur and it is not observed a significant increase of angiogenic factor release. No significant financial relationships to disclose.
A phase II study of S-1 in patients with hormone-refractory prostate cancer: The S-1 Cooperative Study Group (Prostate Cancer) study
Authors: Akaza H. , Ikemoto I. , Namiki M. , Usami M. , Kobayashi M. , Fujimoto H. , Tsukamoto T. , Naito S. 
Published: March 2020

14650 Background: S-1 is an oral fluoropyrimidine antitumor drug that combines three pharmacological agents: tegafur, a prodrug of 5-fluorouracil;gimeracil, an inhibitor of dihydropyrimidine dehydrogenase; and potassium oxonate, which reduces gastrointestinal toxicity. We evaluated the efficacy and safety of S-1 in patients with hormone-refractory prostate cancer. Methods: To be eligible patients (pts) had to have given informed consent, an age of <80 years, elevations of serum prostate specific antigen (PSA) on three consecutive occasions despite effective hormonal therapy and antiandrogen withdrawal for at least 4 weeks, adequate organ function, a PS of 0–2, and a life expectancy of ≥3 months. S-1 was given orally at 40 mg/m2 b.i.d. for 28 consecutive days followed by a 14-day rest period. This 42-day cycle was repeated until confirmation of disease progression. Results: 32 pts were enrolled at 15 institutions. Their median age was 73 years (55 to 79). The median number of courses administered was 2.5 (1 to 11). On the basis of the change in the PSA level, 3 pts had a complete response (CR, <4 ng/ml), and 4 had a partial response (PR, ≥50% decrease), yielding a response rate of 21%. There was no change (NC) in 15 pts, and progressive disease (PD) in 10 pts. The median time to PSA progression was 71 days (95% CI: 44 to 161) overall, 234 days (152 to 435+) in the CR+PR group, and 157 days in the CR+PR+NC group. Grade 3 major toxicity comprised anorexia (3 pts) and anemia (2 pts). No toxicity-related deaths occurred. Conclusions: S-1 is active and well tolerated as a single agent in patients with hormone-refractory prostate cancer. Effectiveness and safety will be confirmed in subsequent large-scale phase II studies. No significant financial relationships to disclose.
HDR brachytherapy combined with hypofractionated EBRT for intermediate-high risk prostate cancer
Authors: Akimoto T. , Hiroyuki K. , Shirai K. , Harada K. , Ebara T. , Ito K. , Yamamoto T. , Nakano T. 
Published: March 2020

14655 Background: To report on biochemical outcome and late complication in pts with localized prostate cancer (LPC) treated with HDR-brachytherapy (HDR-BT) combined with hypofractionated EBRT. Methods: From 06/2000 to 12/2004, 108 pts with intermediate (37 pts.) or high-risk (63 pts.) LPC were treated with hypofractionated EBRT (3 Gy × 17 fr., thrice a week) followed by HDR-BT (5 Gy × 5; 9 pts, 7 Gy × 3; 15 pts, 9 Gy × 2; 76 pts). HDR-BT was administered a week after the completion of the hypofractionated EBRT. The planning target volume was defined as the prostate gland with a 5-mm margin all around, and the planning was conducted based on CT images. Biologically effective doses (BED) to the prostate was between 83–84 Gy. All patient received androgen ablation. Acute and late toxicities were scored according to the EORTC/RTOG morbidity grading scales. Median follow-up duration was 27 months from HDR-BT and 39 months from initiation of androgen ablation. Results: All pts completed treatment. The 5-year actuarial PSA relapse-free survival rates for intermediate and high-risk pts were 100% and 93% respectively. Acute genitourinary (GU) toxicity was 64% in grade 0–1, 31% in grade 2 and 6% in grade 3. Urethral stricture developed in 3%, with a median time from the completion of HDR brachytherapy to the occurrence of 22 months (19–26 months). Ten pts had grade 2 rectal bleeding, with a median time from the completion of HDR brachytherapy to the occurrence of 11 months (7–14 months). No pts developed grade 3 or more severe rectal complication. The incidence of acute and late toxicity did not differ according to the fractionation schema of HDR-BT. Conclusion: Our data demonstrate the successful feasibility of HDR-BT combined with hypofractionated EBRT as a safe method for escalating the total dose to the prostate without significant increasing risk of acute and late GU and rectal toxicities. No significant financial relationships to disclose.
Phase I trial of weekly docetaxel and carboplatin in patients with recurrent squamous carcinoma of the cervix after chemoradiation
Authors: Miller B. E. , Tait D. L. 
Published: March 2020

15023 Background: Treatment for recurrent cervical cancer is palliative; therefore a low side effect profile is important. The combination of docetaxel and carboplatin has been used for the initial treatment of cervical cancer with success. We assessed the tolerance of a weekly schedule in patients with recurrent cervical cancer after chemoradiation. Methods: Patients with advanced recurrent squamous carcinoma of the cervix with a performance status of 2 or better were enlisted in a phase I study evaluating carboplatin at an AUC of 2 and docetaxel at the following dose levels: L1, 25 mg/m2; L2, 30 mg/m2; L3, 35 mg/m2; and L4, 40 mg/m2 i.v. for 3 consecutive weeks of a 4 week cycle. Results: So far 9 patients have been completely evaluated. The median age is 55 years. The median time to recurrence is 13 months. Previous treatment included chemoradiation and in 2 patients additional platinum based chemotherapy. Areas of metastasis included the lung, lymphnodes, abdomen, liver and the pelvis. Dose levels 1 to 3 are completed. A total of 34 courses were administered, an average of 3.6 per patient. One patient received 8 courses. Treatment was discontinued due to progressive disease in 7 patients and due to toxicity in 2 patients one with grade 3 onycholysis and another with a grade 3 allergic reaction to carboplatin. There were no treatment delays due to hematologic toxicity, no grade 2 or higher granulocytopenia, no thrombocytopenia. The mean hemoglobin level dropped from 12 g/dl prior to course 1 to 10.6 g/dl prior to course 3 and 10.2 g/dl prior to course 5. No grade 3 anemia was seen. The main non-hematologic side effects were fatigue, nausea and alopecia, none of which reached grade 3. Accrual on the L4 cohort is still ongoing. Conclusions: The combination of docetaxel and carboplatin given on a weekly schedule is well tolerated in patients with recurrent cervical cancer after chemoradiation. Dose levels similar to those reported for initial treatment can be reached. [Table: see text]
Improvement in neurocognitive function (NCF) correlates with tumor regression after whole brain radiation therapy (WBRT) for brain metastases (BM)
Authors: Li J. , Bentzen S. M. , Renschler M. , Mehta M. P. 
Published: March 2020

1504 Background: Few prospective trials have explored the neurocognitive impact of WBRT in BM patients (pts), complicated by competing effects between benefit from WBRT and deterioration due to disease progression. Methods: 208 pts from the WBRT alone arm (30 Gy) of a phase III trial (PCYC-9801) evaluating motexafin gadolinium in BM were analyzed. NCF was assessed by 8 tests of memory, executive function and fine motor coordination, and correlated to BM volume change by MRI, using Spearman’s rank correlation. Pts with tumor shrinkage below and above the median (45%) were compared for survival and NCF deterioration using Kaplan-Meier analysis. Results: 135 pts (65%) were evaluable for BM volume at baseline and 2 months (mo). Pts were divided into “good” and “poor” responders based on % volume reduction at 2 mo above or below the population median of 45%. The uni-directional hypothesis of improved survival in good responders was significant (P = 0.03, median survival (MS) 300±26 days (d) vs 240±19 d). For all 8 tests, the median time to NCF deterioration was longer in good responders than in poor responders. Largest gains were for an executive function test Trailmaking B (131 d gain, P=0.02), fine motor tests Pegboard non-dominant hand (110 d gain, P=0.05) and Pegboard dominant hand (93 d gain, P=0.02). In 15 mo survivors, statistically significant correlation between tumor shrinkage and NCF preservation was seen for 4/8 NCF tests (r = 0.68–0.88), especially for executive function and fine motor coordination. At early follow-up, the population mean NCF scores were dominated by pts with progressive disease, as reflected by a sharp drop in the mean NCF scores at 4 mo. 15-mo survivors had stable or improving scores, associated with greater reduction in BM volume in the 15 versus 4 mo survivors. Conclusions: WBRT-induced tumor shrinkage correlates with better survival and NCF preservation. NCF is stable or improved in long-term BM survivors. The adverse impact of tumor growth on neurocognitive function appears greater than that of WBRT. [Table: see text]
Three-day regimen of fluorouracil and cisplatin combination chemotherapy for persistence, metastatic or recurrent uterine cervical cancer
Authors: Lee. M. , Yi H. , Song E. , Im M. , Im J. , Lee B. , Kim C. 
Published: March 2020

15049 Background: The five-day infusion of FP(5-fluorouracil, cisplatin) combination therapy is one of the most popular regimens for advanced cervical cancer, which has yield a 50∼60% response rate. There is some variance in the FP combination, for example, longer infusion of FP requiring longer hospitalization as well as causing more discomfort to the patients. This study was designed to assess the therapeutic effect and toxicities of three day regimen of FP combination chemotherapy instead of five day regimen for disseminated or recurrent cervical cancer. Methods: From July 1996 through April 2001, 39 patients with advanced or recurrent cervical cancer were enrolled in the study. The regimen consisted of continuous 12-hour infusion of 5-FU(5-fluorouracil) at 1000 mg/m2/day plus bolus infusion of cisplatin at 25mg/m2/day for 3 days. The treatment was repeated every 3 weeks. Results: Thirty five patients with a median age of 53 years were evaluable for response during the median follow up of 21.5 months. The response rate was 45.7% (4 CR and 12 PR), and the median duration of the overall survival was 45 months. Toxicity was acceptable with no treatment related mortality. Neutropenia in grade 3 or more was seen in 16% with 4 febrile episodes throughout a total 232 cycles. It did not appear alopecia and gastointestinal trouble in grade 3 or more. Conclusions: These results revealed that the toxicity of 3 day regimen of 5-FU and cisplatin is acceptable and the efficacy comparable to that of 5 day regimen. No significant financial relationships to disclose.
A retrospective review of metastatic or recurrent uterine sarcomas treated with ifosfamide and doxorubicin (IMA)
Authors: Guler N. , Hizli D. , Sarici S. , Ocalan R. , Kose M. , Aksoy S. 
Published: March 2020

15053 Background: The prognosis of metastatic uterine sarcoma is poor with median survival reported between 4 to 26 months. We evaluated the efficacy and toxicity of ifosfamide (I) mesna (M) and doxorubicin (A) (IMA) chemotherapy regimen retrospectively in patients (pts) with metastatic, or recurrent uterine sarcomas. Methods: Eligible patients had measurable recurrent or metastatic disease, ECOG PS < 2, had adequate renal, hepatic and hematologic functions. The IMA regimen was ifosfamide 2500 mg/m2 days 1–3, mesna 2500 mg/m2 days 1–3, doxorubicin 60 mg/m2 day 1, repeated every 21 days. Patients were evaluated for response for each two cycles. Results: Thirty-five pts (17 leiomyosarcoma [LMS], 6 malignant mixed mesodermal tumor [MMMT], 5 endometrial stromal sarcoma, 4 carcinosarcoma, and 3 adenosarcoma) were enrolled in this study. The median age was 49 yrs (range, 18–72). Two pts were lost to follow up after the first cycle; one patient had ifosfamide encephalopathy on the third day of the first cycle. Thirty-two pts were assessable for response, toxicity, and survival. Nine pts had prior chemotherapy and 4 pts had radiotherapy. Most frequent metastatic sites were peritoneum, lung and liver. Median period of time from the diagnosis to starting IMA regimen was 14.5 months. A total of 132 cycles of chemotherapy were introduced and for each patient median number of chemotherapy cycles were 4 (range, 1–6). We observed CR in 2 pts; PR in 15 pts. Objective RR was % 48.6 (95% CI, 32% to 67%). Of 17 pts with LMS, 1 CR and 6 PRs were observed. The median progression-free survival time of the responders was 12.0 months. The median progression-free survival time of all patients was 7.0 months. NCI-CTC grade 3 or 4 leucopenia, neutropenia, thrombocytopenia, and anemia occurred in 40%, 55%, 12%, and 13%, respectively. There was no significant nausea/vomiting, nephrotoxicity. Febrile neutropenia was encountered in 6 pts. Dose modifications were required in 4 pts due to myelotoxicity. CNS toxicity was observed in one pts. Conclusions: IMA regimen has moderate anti-tumor activity (48.6%) with acceptable toxicity in pts with recurrent or metastatic uterine sarcomas. No significant financial relationships to disclose.
Bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), and irinotecan for treatment of malignant gliomas
Authors: Vredenburgh J. J. , Desjardins A. , Herndon J. E. , Quinn J. , Rich J. , Sathornsumetee S. , Friedman H. S. , Reardon D. , Gururangan S. , Friedman A. 
Published: March 2020

1506 Background: The prognosis for recurrent malignant gliomas is poor, with a median survival <12 months, median progression-free survival <12 weeks and response rates <20%. Malignant gliomas have high concentrations of VEGF receptors, and the higher the VEGF receptor concentration, the worse the prognosis. Bevacizumab is a humanized IgG1 monoclonal antiblody to VEGF, which is synergistic with chemotherapy for most malignancies. Irinotecan is a topoisomerase 1 inhibitor, and has modest activity against recurrent malignant gliomas. Methods: We report a FDA approved phase II trial of bevacizumab and irinotecan for the treatment of recurrent malignant gliomas. 32 patients were enrolled, 23 with grade IV tumors (glioblastoma multiforme) and 9 with grade III tumors (anaplastic astrocytomas or oligodendrogliomas). All the patients had progressive disease and every patient had received prior radiation therapy and chemotherapy. Patients were treated every other week with bevacizumab 10 mg/kg and irinotecan 125 mg/m2 for patients not taking enzyme inducing anti-epileptic drugs or 340 mg/m2 for patients taking enzyme inducing anti-epileptic drugs. Results: The regimen was well tolerated with no CNS hemorrhages or >grade 1 systemic hemorrhages. Four patients were taken off study for thrombotic complications, 2 pulmonary emboli, 1 deep venous thrombus, and one thrombotic stroke. Two patients were discontinued secondary to grade 2 proteinuria and three were discontinued because they required non-neurosurgical surgery, appendectomy, repair of anal fissures and hip stabilization. The response rate was 63% (19 PRs and 1 CR). The median progression-free survival is 24 weeks. The median overall survival has not been reached, and exceeds 6 months. There have been ten deaths due to disease progression. Conclusions: The combination of bevacizumab and irinotecan is safe and one of the most active regimens against malignant gliomas. [Table: see text]
Cisplatin etoposide in heavily pretreated relapsed ovarian cancer
Authors: Basu D. 
Published: March 2020

15061 Background: Ovarian Cancer is chemo sensitive but recurrence rate is high and patients who are platinum refractory have a poor outcome. Methods: 14 patients with histologically confirmed epithelial ovarian cancer that had relapsed after 3rd line chemotherapy (with platinum combination). Chemotherapy protocol - Cisplatin IVI 50 mg/m2 days 1,8 & 15, Etoposide PO 50 mg Days 1–15; Regime Cisplatin/oral Etoposide repeat 28 days total cycles 2, then oral Etoposide if appropriate. Toxicity Profile: Haematological - neutropenia WHO grade 3 in 20% requiring dose reduction, 64% experienced at least one haematological toxicity; Neutropenic sepsis in 14% of patients but no fatalities. Non-haematological: was mild; Nausea & vomiting - Grade I - II, 86%; Neurotoxicity - Grade I - II, 26%; Nephrotoxicity - Grade I - II, 18%; Fatigue - common, 70%. Results: CA 125 response in 82%; Clinical response with symptom control in 86%; Progression free survival median 6.1 months; Duration of response: 3 months to 18 months (median of 9 months); Stable disease in 7 patients, partial response in 4, complete response occurred in no patients, progression of disease in 2 patients; one patient unable to complete treatment. Conclusion: Chemotherapy for relapsed and heavily pre-treated ovarian cancer is essentially palliative. Symptomatic platinum sensitive patients have a favourable response to rechallenge. Cisplatin-etoposide has considerable activity with tolerable toxicity profile even in platinum refractory patients. Complete information about chances of response and adverse effects should be discussed with all relapsed patients. No significant financial relationships to disclose.
Cyclin B1, D1 overexpression and its correlation with clinical prognostic factors in ovarian carcinoma
Authors: Kim J. W. , Kim Y. T. , Kim H. Y. , Kang M. H. , Kim J. H. , Kim S. H. , Kim S. W. , Yoon B. S. 
Published: March 2020

15067 Background: The change of cell cycle is one of the characteristics of cancer. The various proteins related to the cell cycle have been revealed and their expression in ovarian carcinoma has been demonstrated. Therefore, this study was conducted to determine the expression of cyclin B1, D1 and evaluate the relationship between cyclin B1, D1 and clinical prognostic factors in patients with ovarian carcinoma. Methods: 41 fresh ovarian tissue samples including 36 ovarian carcinomas and 5 normal ovarian tissues were surgically obtained at YUMC from May 2002 to February 2005. Cyclin B1, D1 expression were detected using the quantitative real-time RT-PCR and Western blot analysis. For clinical prognostic factors, age, stage, grade, histopathology, LN metastasis, residual tumor size, CA 125 and DNA flow cytometry were evaluated. Results: By quantitative real time RT-PCR, the mean 2−ΔΔCT value of cyclin B1 and D1 mRNA in ovarian carcinoma was 5.83 ± 12.03, 17.60 ± 22.20, slightly higher than that of the control. (p = 0.67, 0.07). The mean value of relative protein levels of cyclin B1 and D1 in Western blot analysis was also higher in ovarian carcinoma (1.30 ± 0.73, 1.81 ± 1.28, respectively) (p = 0.76, 0.06). No significant relationship of cyclin B1, D1 expression and clinical prognostic factors was observed. Conclusions: The expression of cyclin B1, D1 in ovarian carcinoma was higher than that of the control, although there was no statistical significance. This suggests that cyclin B1, D1 might be involved in the tumorigenesis and the progression of malignancy. Even though there was no significant correlation between cyclin expression and prognostic factors, further studies are needed assessing the relationship between cyclin expression and survival rate to elucidate the role of cyclin as a prognostic factor in ovarian carcinoma. No significant financial relationships to disclose.
Phase II study of extended schedule temozolomide in refractory gliomas
Authors: Berrocal A. , Perez-Segura P. , Gil M. , Balaña C. , Yaya-Tur R. , Yaya-Tur R. , Rodriguez J. , Reynes G. , Garcia-Lopez J. , Gallego O. 
Published: March 2020

1516 Background: Temozolomide resistance is mainly mediated by the enzyme AGT that repair DNA damage in a suicide way. Inhibition of this enzyme is greater when temozolomide is administered in a extended schedule that also obtains higher exposure to the drug. Methods: Primary objective is to assess is extended schedule temozolomide can revert resistance. Patients with bidimensionally measurable high grade glioma refractory to temozolomide defined as either progression during treatment or in the following tree months of drug withdrawal were included. Temozolomide was administered at a dose of 85 mg/m2 daily for 21 consecutive days every 28 days until unacceptable toxicity or progression. Results: Up to now we have included 41 patients, 29 of them available for the first analysis. Mean age is 51.3 (23–77), male 22 (76%), ECOG 0/1/2 7 (24%)/13 (45%)/9 (31%), histology is glioblastoma 18 (61%), anaplastic astrocytoma 9 (31%), anaplastic oligodendroglioma 1 (3.4%) other high grade glioma 1. Fourteen patients received more than one line of chemotherapy before study entrance. 65% were on anticonvulsant therapy mainly with phenytoin 56% or valproic acid 42%. Response to treatment was partial in 2 (6.7%), stable in 9 (31%) progression in 13% (45%) and not assessed in 5. Response only in assessable patients was PR/SD/P 2 (8.3%)/9 (37.5%)/13 (54%). Responses were seen in oligodendroglioma and anaplastic astrocytoma. Median survival has been 5.9 months and time to progression 2 months. 80 courses have been administered with a mean per patient of 2 (1–7). Toxicity has been very mild mainly haematological and grade I and II. 7% of the patients experienced platelet toxicity grade III and 3.5% neutropenia grade III. Non haematological toxicity was mainly transaminase elevation grade I to II in 24% of patients and nausea and vomiting grade I to II in 31%. Conclusions: Extended schedule temozolomide is an active regimen in resistant patients with moderate toxicity. Resistance to temozolomide may be reverted by extended schedule of administration [Table: see text]