bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docetaxel and cisplatin combination chemotherapy for advanced epithelial ovarian cancer with bulky residual disease
Authors: Shaharyar A. , Shabbir K. , Hafeez M. , Alauddin Z. , Rehman E. U. 
Published: March 2020

15030 Background: The combination of docetaxel and cisplatin as an alternative to the gold standard carboplatin and paclitaxel chemotherapy has not been explored in our patients. Docetaxel is more potent of the taxanes, therefore, this combination might yield a better outcome. This phase II study was designed to evaluate the efficacy and toxicity of docetaxel and cisplatin combination in epithelial ovarian cancer with bulky residual disease. Methods: Thirty-two new patients were enrolled between November 2003 and August 2005. Eligible patients had histopatholgically confirmed epithelial ovarian cancer, were older than 18 years and had FIGO stage IIC-IV cancer with bulky residual disease after primary cytoreductive surgery. Patients had a KPS >70 with adequate marrow and hepatic function. Patients with creatinine clearance by Cockroft-Gault formula of >60 ml/min were included. Written informed consent was obtained. Patients with diabetes mellitus, peripheral neuropathy, or cardiac co morbidity were excluded. Docetaxel and cisplatin were given at a dose of 75 mg/m2 each on day-1 of a 21-day cycle. Dexamethasone 8 mg was given thrice before and thrice after and tropisetron 5mg was given one hour before and 12 hours after chemotherapy. Docetaxel was given in 250 ml of NaCl in one-hour followed by cisplatin 75 mg/m2 in 1L of NaCl in 3 hours with pre and post hydration. NCI toxicity criteria version 2.0 and RECIST was used for evaluation. Results: Thirty patients were evaluable for response and toxicity. Final evaluation revealed CR in 12 (40%) (95% CI, 22.7–59.4%), PR in 14 (46.6%) with an ORR of 86.6% (95% CI, 69.3–96.2%). Three (10%) had SD and 1 (3.33) had PD. Grade 2 toxicity included alopecia 18 (60%), vomiting 6 (20%), diarrhea 7 (23.3%) and stomatitis in 5 (16%). Grade 3 and 4 neutropenia were seen in 12 (40%) and 9 (30%) respectively. Sensory neuropathy of grade 1 and 2 was seen in 4 (13.3%) and 2 (6.7%) respectively. Conclusion: Docetaxel and cisplatin combination chemotherapy is an effective and safe regimen in epithelial ovarian cancer with bulky residual disease. It gives a high overall response rate and has a manageable toxicity profile. No significant financial relationships to disclose.
Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy in carcinoma of uterine cervix
Authors: Goel V. , Singh. J. K. , Pandey M. K. 
Published: March 2020

15032 Background: Studies have described decreased pelvic control & survival rates in invasive ca cervix when overall time in definitive RT is prolonged. We evaluated impact of timing of brachytherapy on outcome. Methods: Retrospective analysis of 338 patients of ca cervix treated with radical RT from Jan 2002 to Dec 2002 at Mahavir Cancer Sansthan Patna. The median age was 50 yrs (23–80 yrs). 73% patients were postmenopausal. Histopathology was Squamous Cell in 97% patients. Most common presenting complaints were bleeding P/V (92%) & discharge P/V (82%); with stage I (3%), II (35%), III (43%), IV (5%), unknown stage in 14% cases. Results: Records of 338 patients (Stage IB to III) treated with definitive irradiation (combination of EBRT & ICRT) were reviewed with reference to loco regional control, distant failure and its correlation with patient and tumor variables including OTT. Out of 302 patients who received complete RT, 24 received 60 Gy in 30 fractions as they were found to be unsuitable or were unwilling for ICRT. The rest received a dose of 50 Gy/25 Fr to 50.4 Gy/28 Fr over a median duration of 37 days. 30 patients received concomitant chemo radiation (cisplatin 40 mg/m2/4 cycles). 276 patients received ICRT (dose 21 Gy in 3 Fractions with a median gap of 43 days (range 5–111) after completion of ERT. The median OTT for completion of ERT & ICRT was 75 days (range 54–177). At an average follow up of 18- 24 months residual disease was seen in 2 cases (0.6%), local recurrence in 14 cases (4%) & distant failure in 14 cases (4%). Post RT complications were seen in 4.7% cases and included small bowel obstruction in 6 cases, VVF in 4 & RVF in 6 cases. Significant correlation was seen between OTT and rate of loco regional recurrences. All local recurrences were seen when OTT was more than 75 days. No significant correlation could be drawn between age, Hemoglobin, tumor histology, & bulky vs. non bulky tumor on loco regional and distant failure. Conclusions: Longer radiotherapy completion time was found to be associated with diminished survival outcomes for patients treated radically for carcinoma cervix. The significance of this observed association requires further investigation & correction to keep OTT as short as possible. No significant financial relationships to disclose.
A phase II study of combination CPT-11 and docetaxel in patients with ovarian carcinoma refractory or resistant to combination paclitaxel and carboplatin
Authors: Enomoto T. , Yoshino K. , Yamasaki M. , Nishio Y. , Wakimoto A. , Miyake T. , Fujiwara K. , Takemura M. , Ito K. 
Published: March 2020

15036 Background: To investigate the efficacy and toxicity of combination irinotecan and docetaxel in patients with ovarian carcinoma refractory (not responded) or resistant (relapsed within 6 months after the last chemotherapy) to the first line chemotherapy with combination paclitaxel (175mg/m2) and carboplatin (AUC=5). Methods: 30 refractory patients and 28 resistant patients with measurable disease were treated with combination irinotecan (60 mg/m2) and docetaxel (30 mg/m2) at days 1 and 8 every 3 weeks for more than 2 courses. Results: The average number of courses administered was 2.6 for refractory cases and 3.4 for resistant cases. The average number of courses administered was 2.6 for refractory cases and 3.4 for resistant cases. Using RECIST criteria, 2/28 (7%) resistant cases responded completely, 6/30 (20%) of refractory cases and 6/28 (21%) resistant cases were responded partially. 16/30 refractory cases and 14/28 cases progressed. Grade 3–4 toxicities were leukopenia (31%) neutropenia (36%) thrombocytopenia (8%) and diarrhea (6%). Conclusions: Combination chemotherapy of CPT-11 and Docetaxel at days 1 and 8 every 3 weeks is a regimen with moderate toxicity and good compliance, and shows some response to those patients who are refractory or resistant to the first-line chemotherapy with paclitaxel and carboplatin with a response rate of 20% and 29%, respectively. No significant financial relationships to disclose.
Analysis of third-line and fourth-line chemotherapy for recurrent ovarian cancer treated with first-line platinum/taxane regimens
Authors: Nishio S. , Katsumata N. , Matsumoto K. , Tanabe H. , Kato Y. , Yonemori K. , Kouno T. , Shimizu C. , Ando M. , Fujiwara Y. 
Published: March 2020

15045 Background: Limited information is available regarding to the usefulness of third-line chemotherapy (TLC) and forth-line chemotherapy (FLC) for recurrent ovarian cancer treated with first-line platinum/taxane (PT) regimens. Methods: We retrospectively reviewed the medical records of patients (pts) with ovarian cancer treated with PT regimens at the National Cancer Center Hospital from 1998 to 2004. The aim of this study is to investigate the important clinical factor such as response rate (RR), time to treatment progression (TTP), overall survival (OS) and predictor of response to TLC and FLC. Kaplan-Meier method was used for estimating TTP and OS. Wilcoxon test was performed for survival times and p-values < 0.05 were considered to be statistically significant. Results: There were 183 pts received first-line PT regimens in study period, 77 of 183 pts received second-line chemotherapy (SLC), 61 of 77 progressed after SLC and 55 of 61 pts received TLC. The RR to TLC was 34.5%. The median TTP was 5 months (mo) (range; 1–19 mo) and the median OS was 12 mo (range; 2–38 mo). The TLC regimen was consisted of P and/or T regimens of 36 pts and the other regimens of 19 pts. The RR according to the duration of response of previous chemotherapy (DRPC) (< 6 mo and ≥ 6 mo) were 31.4% and 37.3%, respectively. The median OS of DRPC (< 6 mo and ≥ 6 mo) were 8 mo (range; 2–33 mo) and 12 mo (range; 2–38 mo), respectively (p = 0.002). After TLC 47 pts progressed and 29 pts received FLC. The RR to FLC was 27.5%. The median TTP was 3 mo (range; 0–11 mo). The median OS of 18 pts who didn’t receive FLC and 29 pts received FLC were 2 mo (range; 2–16 mo) and 7 mo (range; 2–25 mo), respectively (p = 0.01). The RR according to DRPC (< 4 mo and ≥ 4mo) were 22.2% and 30%, respectively. The median OS of DRPC (< 4 mo and ≥ 4 mo) were 3 mo (range; 2–23 mo) and 6 mo (range; 2–25 mo), respectively (p = 0.4). Conclusions: The DRPC is considered to be predictor of response to TLC but not to FLC. Giving TLC and FLC if the pts have tolerable may improve OS, however this analysis is prone to several well-established potential biases and limitations. Further prospective study is warranted. [Table: see text]
Diagnostic and prognostic significance of a t(1;19)(q10;p10) in patients (pts) with low-grade oligodendroglioma and astrocytoma: NCCTG 94–72–53
Authors: Jenkins R. B. , Ballman K. V. , Giannini C. , Arusell R. M. , Blair H. , Passe S. , Flynn H. , Brown P. , Shaw E. G. , Buckner J. C. 
Published: March 2020

1505 Background: Combined deletion of chromosomes 1p and 19q is associated with improved prognosis in pts with anaplastic oligodendroglioma. We recently discovered that the combined deletion is mediated by a chromosome 1;19 translocation: t(1;19)(q10;p10). The prognostic significance of this alteration in pts with low-grade gliomas is not known. Methods: Paraffin-embedded tumor tissue was obtained from 134 pts enrolled in two NCCTG trials for newly-diagnosed low-grade glioma: 86–72–51: a randomized phase III trial of 50.4 Gy vs 64.8 Gy radiation therapy (RT) and 93–72–02: a phase II trial of PCV for 6 cycles followed by RT. Interphase fusion of a CEP1 probe and a BAC contig probe for 19p12 was used to detect the 1;19 translocation. Analysis of 1p and 19q deletions had been previously performed by FISH. Kaplan-Meier distributions of overall survival (OS) and progression-free survival (PFS) for pts whose tumors did or did not exhibit CEP1/19p12 fusion were compared using the Wilcoxon test. Results: Of 134 pts, CEP1/19p12 fusion testing was informative for 92. CEP1/19p12 fusion prevalence was 55% among 42 oligodendrogliomas, 47% among 30 mixed oligoastrocytomas, and 5% among 20 astrocytomas. 91% of gliomas with and 11% without 1p/19q deletion had CEP1/19p12 fusion (p<0.0001, chi-square test). The frequency of the t(1;19) by tumor histology, as well as median and 5-year progression-free and overall survival are provided in the table . Conclusions: Our results strongly suggest that a t(1;19)(q10;p10) mediates the combined deletion of 1p and 19q in human gliomas. Like combined 1p and 19q deletion, the 1;19 translocation is associated with superior progression-free and overall survival in low-grade oligodendroglioma patients. FISH analysis of the t(1;19) will likely be a more sensitive and specific means to assess 1p and 19q status in patients with gliomas. (Supported in part by CA85799, CA108961 and NCCTG grants CA25224 and CA114740) [Table: see text] No significant financial relationships to disclose.
Eukaryotic elongation factor 1 alpha 2 alone is not sufficient to cause tumorigenicity in immortalized and neoplastic ovarian cell lines
Authors: Leiser A. L. , Rosales N. , Spriggs D. 
Published: March 2020

15051 Background: EEF1a2 is amplified and overexpressed in 25% of ovarian tumors. Previous studies have shown EEF1a2 to have oncogenic and tumorigenic properties in rodent fibroblasts. However, its role in the tumorigenesis and behavior of human ovarian carcinomas is not known. Methods: Stable expression of EEF1a2 cDNA in both T80 immortalized human ovarian surface epithelial cells and SKOV-3 cell line was followed by standard proliferation assays, soft agar assays for anchorage independent growth, cell cycle analysis, mouse xenograft injections, evaluation for changes in factors such as VEGF and ras and susceptibility to CDDP. Transient transfections with 3 different siRNA’s to EEF1a2 were performed in both cell lines. Results: Stable expression of EEF1a2 was detected by Western Blot and IP. Compared to vector only control, transfection with pCMVTag2B EEF1a2 vector did not change proliferation in either cell line. Anchorage independent growth was slightly higher in the T80 transfected cells. Cell cycle and expression of VEGF and ras were not different than control. IC50 of CDDP was similar between the transfected and control cell lines. No size difference was seen in SKOV transfected and control xenografts. T80 controls grew larger and more frequent tumors than transfected controls. Transient transfection of T80 with siRNA did not result in changes in anchorage independent growth. Conclusion: EEF1a2 alone is not sufficient to act induce tumorigenicity, affect tumor growth rate or drug susceptibility in human ovarian epithelial cells. Experiments utilizing stable siRNA vectors specific to EEF1a2 are underway, as well the combination of EEF1a2 with recognized ovarian tumor oncogenes. No significant financial relationships to disclose.
Control of acute toxicity with amifostine and pelvic chemoradiotherapy
Authors: Tate M. , Wilson L. , Silverman C. , Helm W. , Parker L. , Metzinger D. , Paris K. , Carrascosa L. , Yashar C. 
Published: March 2020

15058 Background: Amifostine is an FDA approved normal tissue radioprotector for head and neck carcinoma. Several studies have also demonstrated a radioprotective role in pelvic malignancies. However, literature also shows that amifostine has substantial toxicity. We examined patient compliance with combined chemoradiotherapy and daily amifostine subcutaneous injections, the incidence of acute toxicity, and the efficacy of interventions. Methods: Patients undergoing pelvic radiotherapy and concurrent chemotherapy were eligible. Patients received daily subcutaneous injections of 500 mg amifostine 30 to 60 minutes before radiotherapy. Injection pain, erythema, and rash were recorded daily, as was patient blood pressure before and after receiving amifostine and radiotherapy. Treating physicians evaluated patients at least weekly. Symptoms were recorded and graded using the NCI Common Toxicity Criteria. The protocol was amended early in accrual to include nausea prophylaxis guidelines. Results: Nineteen patients have been entered into this study. Fourteen had cervix cancer, four had rectal cancer, and one had anal cancer. Four patients (21%) received <1 week of amifostine. Seven (37%) received <50% of their planned injections. Fifty three percent received >80% of their injections, while 32% received the full course of amifostine. Of those that prematurely discontinued amifostine, 1 withdrew before receiving any injections, 1 transferred to another facility, 6 withdrew because of nausea, 2 secondary to rash, 2 secondary to injection pain. One developed paresthesias. Of those that withdrew because of nausea, all but one received >50% of the planned injections. Twenty six percent experienced grade 3 nausea. When comparing patients that did not receive nausea prophylaxis with those that did, grade two or three nausea dropped from 100% to 29%. No patients developed grade 3 rash. Two patients experienced hypotension. Nine patients (47%) complained of injection site pain. Conclusions: Subcutaneous amifostine is reasonably well tolerated when used with pelvic radiotherapy. Nausea was a significant side effect seen in this study. Assuring adequate hydration and use of prophylactic antiemetic medication significantly decreased nausea. [Table: see text]
Lessons from ovarian cancer patients with more than 10 years survival
Authors: Kudoh K. , Takano M. , Kita T. , Yoshikawa T. , Furuya K. , Kikuchi Y. 
Published: March 2020

15059 Background: Purpose of this retrospective study is to explore predictive factors for long-term survival in patients with primary epithelial ovarian carcinoma. Methods: Total 161 patients treated from March 1983 to December 1994 at the National Defense medical College hospital were enrolled in this study. Profiles and characteristics of patients with long-term survival were retrospectively examined. Results: All patients with stage IA-B or IIA-B survived more than 10 years although 2 of patients with stage IA and IB tumor were dead of primary disease and one patient was dead of other disease after more than 10 years follow-up. More than half of patients with stage IC, IIC or IIIA-B survived more than 10 years, while 10-years’ survival rates of patients with stage IIIC or IV were only 10% with marked increase of death by primary disease. All patients with stage I or IIA-B without residual tumor after initial surgery survived more than 10 years. Although long-term survival rates of patients with stage IIC or IIIA-B were higher in patients without residual tumor after initial surgery, 6 out of 7 patients with stage IIIC or IV had residual tumor. Analysis of 70 patients with stage III or IV ovarian cancer revealed that residual tumor size, histologic types and response to initial chemotherapy affected significantly long-term survival. Conclusions: We demonstrated that predictors for long-term survival were stage, residual tumor size after initial surgery, histology and response to initial chemotherapy. [Table: see text] No significant financial relationships to disclose.
Temozolomide (TMZ) 3 weeks on/1 week off in the treatment of progressive low grade gliomas: A phase II GICNO study
Authors: Brandes A. A. , Tosoni A. , Cavallo G. , Scopece L. , Gardiman M. , Berti F. , Pasetto L. M. , Ferrarese F. , Blatt V. , Ermani M. 
Published: March 2020

1514 Background: Encouraging results have been obtained inlow grade glioma (LGG) patients (pts) following TMZ therapy at the standard schedule of 200 mg/m2 for five-days every 28 days. A continuous dose TMZ schedule leads to DNA repair enzyme AGAT level depletion in tumor cells. By removing TMZ-produced methyl adducts, AGAT contributes to the development of resistance to alkylating agents. Methods: Pts with a diagnosis of LGG received TMZ 75 mg/m2/d for 21 days every 28 days at clinical or radiological progression. MiniMax Simon’s design with P0=0.2, P1=0.4, α=0.1, β=0.1 was used and a sample size of 36 pts was planned. The primary end-point was to assess the response rate (RR=CR+PR), and the secondary end-point to investigate the correlations between 1p/19q deletions by FISH and MGMT promoter methylation by methylation specific PCR (MSP). Results: 22 oligodendroglioma (O), 4 oligoastrocytoma (OA) and 10 astrocytoma pts (A) were enrolled (median age of pts 47 years, range 24–69 years; median KPS 90, range 50–100). Eleven pts were pre-treated with radiotherapy; 5 (13.5%) had enhancing lesion at MRI scan. RR was 30.5% (11 PR), all RR being obtained in pts with non-enhancing lesions; 20 pts (55.5%) had disease stabilization; 8/11 responders were assessable for 1p/19 q deletions and, of these, 6 pts (75%) had combined 1p/19q deletion. Median PFS was 17.4 months (interquartile ranges, 9.3–25). PFS at 1 year was 73% (SE 8%). Preliminary data on molecular assessment are: 29 pts were assessable for 1p and 19q deletions, both being present in 19 pts (65.5%). 1p/19 q loss was significantly greater in pts with O/OA than A (p=0.01). Of 11 assessable pts, 7 (63.6%) presented MGMT promoter gene methylation and all 7 pts presented 1p and 19q deletions (p=0.03). Grade 3 lymphopenia was observed in 4 pts (11.1%) and 1 patient had G2 reversible renal toxicity. Conclusion: TMZ for 21 days every 28 is an active and well tolerated regimen in pts with LGG. The analysis to verify any correlation between molecular markers and clinical outcome is ongoing. [Table: see text]
An update of phase II results from RTOG 0211: A phase I/II study of gefitinib with radiotherapy in newly diagnosed glioblastoma
Authors: Chakravarti A. , Berkey B. , Robins H. I. , Guha A. , Curran W. J. , Brachman D. , Shultz C. , Mehta M. 
Published: March 2020

1527 Background: The epidermal growth factor receptor (EGFR) pathway is commonly deregulated in GBMs and its activity has been associated with treatment resistance in preclinical models. Accordingly, the Radiation Therapy Oncology Group (RTOG) recently conducted a Phase I/II study of Gefitinib, an EGFR tyrosine kinase inhibitor, in combination with radiotherapy for newly-diagnosed glioblastoma (GBM) patients. Methods: 178 GBM patients were entered on RTOG 0211 (Phase I: 31 patients and Phase II: 147 patients). The maximum tolerated dose (MTD) of Gefitinib was determined to be 500mg in non-EIACD patients, and the Phase II component of RTOG 0211 was continued at this dose level during radiation and as maintenance for 18 months afterward or until disease progression. Results: 119/147 patients completed treatment per protocol and/or with acceptable deviation. The median survival time for all patients in the study was 11.0 months. Progression-free survival was 5.1 months for all patients. When considering only patients who were treated per protocol, the median survival of RTOG 0211 patients was 11.5 months, compared to 11.0 months for historical controls treated in previous RTOG studies (p=0.14). RPA Class IV patients appeared to derive the greatest benefit from Gefitinib when combined with radiotherapy compared to historical controls, although not reaching statistical significance. Molecular and genetic profiling efforts are underway to determine which GBM patients derive greatest benefit from Gefitinib in the upfront setting, which will be reported at the time of the annual meeting. These include markers such as EGFRvIII and PTEN, which have been recently reported to be associated with response to anti-EGFR agents in the recurrent setting, and members of key signal transduction pathways regulated by EGFR. Conclusions: The observed survival advantage of newly-diagnosed GBM patients treated with Gefitinib in combination with radiotherapy compared to historical controls treated on previous RTOG studies does not reach statistical significance. Molecular and genetic profiling efforts are underway to identify subsets of GBM patients who might derive the greatest benefit from Gefitinib in the upfront setting. No significant financial relationships to disclose.