bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of combination irinotecan and oral etoposide chemotherapy in recurrent ovarian cancer: A Tohoku Gynecologic Cancer Unit (TGCU) study
Authors: Kumagai S. , Shoji T. , Yokoyama Y. , Takano T. , Mizunuma H. , Yaegashi N. , Sugiyama T. 
Published: August 2020

5558 Background: Various problems still exist in the management of recurrent ovarian cancer and there are limited treatment options especially for the platinum resistant patients (pts). We conducted a phase II study to evaluate the efficacy and safety of the combination irinotecan/oral etoposide chemotherapy. Methods: Eligibility criteria included recurrent ovarian cancer with measurable disease or positive CA125, preserved organ function, and aged 20–75. Treatment was conducted with irinotecan (60 mg/m2 iv, day 1, 15) and oral etoposide (50 mg/body day 1–21), q 28 days until disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) and secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: 38pts were enrolled on this study from May 2003 to April 2007, and all pts were eligible. Median age was 57 yrs (range 37–74). PS 0 in 24 pts, 1 in 10 pts, and 2 in 4 pts. Median number of previous regimen was 2 (range 1–4). Median treatment cycles were 6 (range 2–27). RR (CR+PR) was 18/38 (47.4%), and CR+PR+SD rate was 31/38 (81.6%). Grade 3/4 adverse effect included leukopenia (50.0%), neutropenia (52.6%), anemia (18.4%) and thrombocytopenia (2.6%), nausea/vomiting (7.9%) and diarrhea (2.6%). Treatment-related death was not observed. Median PFS was 7 months (range 1–33) and OS was 19 months (range 4–60). Among 20 pts with platinum resistant cases, RR was 6/20 (30.0%), CR+PR+SD rate was 14/20 (70.0%), median PFS was 6 months (range 1–33), and OS was 24 months (range 5–60). Conclusions: Combination irinotecan/oral etoposide chemotherapy can achieve a superior management for the recurrent ovarian cancer without declining QOL, and also has the possibility to be one of the most effective regimens as second-line chemotherapy. No significant financial relationships to disclose.
Randomized phase II study of decitabine in combination with carboplatin compared with carboplatin alone in patients with recurrent advanced ovarian cancer
Authors: Glasspool R. M. , Gore M. , Rustin G. , McNeish I. , Wilson R. , Pledge S. , Paul J. , Mackean M. , Halford S. , Kaye S. ,   on behalf of the Scottish Gynaecological Cancer Trials Group
Published: August 2020

5562 Background: Experimental and clinical data (Gifford et al, Clin Cancer Res. 2004) indicate the potential importance of methylation in mediating resistance to carboplatin in ovarian cancer. A previous phase I trial (Appleton et al, J Clin Oncol. 2007) established the feasibility of combining carboplatin with the demethylating agent decitabine on a day 1 + 8 q4 weekly (w) schedule and PD data provided evidence of target cell demethylation. Methods: Patients (pt) with ovarian cancer relapsing 6–12 months following first line treatment were randomised to receive either 6 cycles of carboplatin AUC 6 q4 w (Arm A), or 90 mg/m2 decitabine as a 6 hour infusion on day 1 and carboplatin AUC 6 on day 8 q4 w (Arm B). The primary endpoint was response rate. An interim analysis was planned after 11 patients were enrolled into Arm B. Results: 29 pt were enrolled. After the first 4 pt had been treated (at 90 mg/m2 decitabine) the frequency of dose delays due to neutropenia was considered unacceptable, and therefore the starting dose of decitabine was reduced to 45 mg/m2 for the subsequent 11 pt. 7 out of 14 pt in Arm A completed 6 cycles compared with 0 of 11 in Arm B (at 45 mg/m2 decitabine). Grade 2/3 hypersensitivity reactions were more common in Arm B than Arm A (64% vs. 21%), as were prolonged treatment delays due to neutropenia (36% vs. 10%). At the interim analysis, in the 11 pt treated with 45mg/m2 (Arm B), there were no RECIST responses, while 2 pt had short-lived CA125 responses (59 and 63 days). In contrast 6 of 14 patients in Arm A had RECIST responses consistent with the expected efficacy of carboplatin in this population. Conclusions: The lack of efficacy, as well as the difficulties in treatment delivery in Arm B, led the project team to conclude that the study should be closed. With this dose and schedule, decitabine is ineffective in reversing carboplatin resistance. Further investigations are ongoing to understand (a) the apparent increased incidence of hypersensitivity and (b) the trend towards reduced efficacy in Arm B. [Table: see text]
Clinical presentation and sensitivity to platinum-based chemotherapy (CT) of mucinous advanced epithelial ovarian carcinoma (M-AEOC): The GINECO-Group experience
Authors: Alexandre J. , Ray-Coquard I. , Selle F. , Floquet A. , Cottu P. , Weber B. , Falandry C. , Lebrun D. , Pujade-Lauraine E. 
Published: August 2020

5572 Background: M-AEOC have been consistently associated with worse prognosis than the most common serous (S) histologic subtype; however it is unclear if this observation is related to more aggressive clinical presentation and/or chemoresistance behaviour. Methods: Data from four randomized phase III and one phase II AEOC first-line clinical trials were collected and retrospectively analyzed. Study selection criteria included: completed study, platinum-based chemotherapy and stage IIB to IV AEOC patients (pts). Results: Data on 1118 pts with advanced AEOC were analysed, of whom 94% were treated with paclitaxel-carboplatin-based CT. 786 pts had S-AEOC and 54 pts M-AEOC (5%). Peritoneal metastasis (mets) appeared more limited in M- than in S-AEOC pts since stages IIB-IIIB were more frequent (31% versus 19%, p = 0.001) and complete resection more frequently obtained (45% of stage II-III pts versus 29%, p = 0.06) in M-AEOC. Extra-peritoneal mets (stage IV) were more frequent in M- than in S-AEOC pts (30% versus 15%, p = 0.004), specially liver mets (44% of stage IV pts versus 23%, p = 0.06). Progressive disease during CT was observed in 40% of pts with stage IV M-AEOC. Progression free survival (PFS) was worse in M- than in S-AEOC pts both in stage IV (1y PFS: 15% versus 51%, p = 0.02) and in stage III with optimal resection (2y PFS: 42% versus 66%, p = 0.05). Conclusions: Compared to S-AEOC, M-AEOC is characterized by more limited peritoneal carcinomatosis but more frequent liver mets. M-AEOC appears to be a highly chemoresistant disease and complete resection of peritoneal mets is unable to reverse its adverse prognosis. New therapeutics options are needed. No significant financial relationships to disclose.
Prognostic value of gene expression of p63 by microarray analysis in estrogen receptor positive and negative breast cancer
Authors: Hanker L. C. , Karn T. , Rody A. , Ruckhäberle E. , Solbach C. , Kaufmann M. 
Published: August 2020

566 Background: The protein 63 (p63) represents a member of the p53 family (p53/p63/p73) located on chromosome 3q27. This gene family seems to play an important role in carcinogenesis and its members may act as oncogenes or tumor suppressor genes. P63 is overexpressed in many different tumors like head and neck cancer, lung cancers, uterine tumors and breast cancer, and has been associated with poor prognosis in some studies. P63 was found to be overexpressed in a subset of highly aggressive breast cancers that represent a basal and myoepithelial phenotype and have a poor clinical outcome. This protein seems to be a specific myoepithelial cell marker in normal breast tissue and might represent a prognostic factor in breast cancer. Methods: Large scale analysis was performed using Affymetrix microarray data from n=1581 breast cancer patients to evaluate p63 expression. Results: P63 expression showed a strong correlation with patient's age (χ2-test, p < 0.001), tumor size (p < 0.003), proliferation rate (p < 0.001), Topo2α expression (p = 0.001) and estrogen receptor expression (p = 0.017). Survival analysis of all patients with available follow up data (n = 1263) showed a significant difference due to high and low p63 expression (log rank p < 0.001). Patients with a low p63 expression had the worst prognosis. In univariate Cox regression analysis p63 showed a hazard ratio (HR) of 1.61 (95% CI 1.31–2.00, p < 0.001) for disease free survival. This prognostic impact remained significant when samples were stratified by estrogen receptor status. High expression of p63 was significantly associated with longer OS in both ER negative (n = 334, log rank p = 0.022) and ER positive (n = 929, log rank p < 0,001) breast cancer. The prognostic impact of p63 expression was independent of Ki67 expression (p = 0.011 and p = 0.001 for high and low Ki67, respectively). Moreover a worse prognosis of low p63 expressing tumors was found in both subgroups of ErbB2 positive tumors (p < 0.001) and ErbB2 negative tumors (p < 0.001). Conclusions: P63 expression is a prognostic factor in both ER positive and negative breast cancer and could be helpful for risk assessment in breast cancer patients. No significant financial relationships to disclose.
Effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole
Authors: Safra T. , Bernstein Molho R. , Stephansky I. , Yaal-Hahoshen N. , Inbar M. , Ackerstein A. , Geffen D. 
Published: August 2020

599 Background: Adjuvant treatment with aromatase inhibitors (AIs) in postmenopausal women (PMW) with early breast cancer (EBC) can be associated with decreased bone mineral density (BMD) and increased risk of osteoporosis and fractures. Tamoxifen (TAM) has bone protective effect. BIG 1–98 recent, 71 months update suggests that sequential therapy of TAM and letrozole (LET) in either order, have similar efficacy to 5 years of LET. This study is designed to evaluate the efficacy and safety of zoledronic acid (ZA) in preventing AIs bone loss after 2.5 years of TAM. Methods: This is an open-label, randomized phase II study of PMW with hormone receptor positive EBC previously treated with TAM for the last 2.5 years (with BMD T score ≥ -2.5). Patients are randomly assigned to receive LET (2.5mg/ daily) ± ZA. Patients on treatment arm receive 4 mg IV ZA every 6 months for 2 years. All patients are being evaluated every 6 (0–36) months with blood chemistry and BMD test. All patients receive vitamin D and calcium supplement. A comparison between groups and between time points is performed by one-way ANOVA with repeated measures using the Mixed model. Results: Seventy four patients were screened. Median age was 58.9 years (46.5–83.6). All patients are alive, one had an ipsilateral recurrence. Seventy two patients were evaluable (2 were screening failure), 33 randomized to receive ZA and 39 to the control group. Median follow-up (FU) was 18.2 months (1–47). At this point in time a significant interaction between groups and time trend was found, in favor of ZA treated group in lumbar T score (p = 0.0055). While in the control group a significant decline in lumbar BMD was noticed (p = 0.008), in the treatment group BMD did not change over time (p = 0.2971). Adverse events with ZA were mild with some flue like syndrome. No serious renal adverse event or ONJ (osteonecrosis of jaw) cases were reported. ZA was safe and well tolerated. Conclusions: Sequential adjuvant treatment with TAM and AIs in PMW with EBC can be associated with decreased BMD and increased risk of osteoporosis. In our study, LET-induced bone loss increases with time. A significant benefit in BMD was seen when ZA was added to LET. A longer follow up is needed to evaluate the real magnitude of ZA protective effects. [Table: see text]
Final results of a randomized phase III trial comparing induction chemotherapy with cisplatin/5-FU or docetaxel/cisplatin/5-FU follow by chemoradiotherapy (CRT) versus CRT alone as first-line treatment of unresectable locally advanced head and neck cancer (LAHNC)
Authors: Hitt R. , Grau J. J. , Lopez-Pousa A. , Berrocal A. , Garcia Giron C. , Irigoyen A. , Sastre J. , Martinez J. , Cortes-Funes H. , Cruz-Hernandez J. 
Published: August 2020

6009 Background: Induction chemotherapy (IC) with TPF isa standard regimen for patients (pts) with locally advanced head and neck squamous cell carcinoma (N Engl J Med. 2007;357:1705–1715). However, CRT alone is standard treatment for unresectable LAHNC. We designed a trial to compare two different regimens of IC followed by CRT versus CRT alone in pts with unresectable LAHNC. Methods: Pts with unresectable, measurable LAHNC, adequate organ function, and ECOG 0–1 were enrolled and stratified according to primary tumor site. (IC) regimens (3 cycles): PF (cisplatin 100 mg/m2 day [d] 1, then 5-FU 1,000 mg/m2 continuous infusion [CI], d1–5, q21d); TPF (docetaxel 75 mg/m2 d1, cisplatin 75 mg/m2 d1, 5-FU 750 mg/m2 CI, d1–5, q21d plus G-CSF and ciprofloxacin). All pts were to receive CRT, consisting of conventional radiotherapy up to 70 Gy plus cisplatin 100 mg/m2 d 1, 22, 43. The primary end point was time to treatment failure (TTF) for (IC) vs. no (IC); secondary endpoints included locoregional control (LRC) rate and safety; 438 pts were needed to demonstrate a 15% difference in treatment failure (death, progression, surgery, other treatments) with α = 0.05, β = 0.2. Results: From December 2002 to June 2007, 439 pts were enrolled: IC 311 pts (TPF 155, PF 156) and CRT 128 pts. The majority of pts were: ECOG 1 (70%); oropharynx and oral cavity (63%); T4 (75%); N2-N3 (61%). In evaluable pts (at least 1 cycle), the median TTF was 12.5 months with IC/CRT vs. 4.9 months with CRT alone (p < 0.001; HR 0.57; 95%CI 0.44–0.74); LRC rate was 60.9% IC/CRT vs. 44.5% CRT (p = 0.003; OR = 0.52; 95%CI 0.3–0.81). Grade 3–4 adverse events (IC/CRT vs. CRT) occurred in 83% vs. 69% of pts and included febrile neutropenia (10% vs 1%), and stomatitis (43.7% vs 37%). Conclusions: This is the first phase III trial to demonstrate that (IC) followed by CRT significantly increases TTF and LRC compared with CRT alone in pts with unresectable LAHNC. IC/CRT should now be considered standard treatment for these pts. No significant financial relationships to disclose.
Phase I/II dose escalation study of OncoVexGM-CSF and chemoradiotherapy (CRT) in untreated stage III/IV squamous cell cancer of the head and neck (SCCHN)
Authors: Harrington K. , Hingorani M. , Tanay M. , Matthews J. , Newbold K. , Renouf L. , Coffin R. S. , McNeish I. , Nutting C. 
Published: August 2020

6018 Background: OncoVEXGM-CSF is a gene deleted (ICP34.5-/ICP47) oncolytic HSV-1 that encodes human GM-CSF. OncoVEXGM-CSF causes direct oncolytic tumour cell destruction and immune activation by releasing tumour antigens and GM-CSF, effects that may co-operate with CRT to increase loco-regional control in SCCHN. Methods: Patients (pts): Stage III/IVA SCCHN, N1-N3, ECOG 0–1, normal haematologic, biochemical, immune function. Pts received CRT (70 Gy/35 fractions with concomitant cisplatin 100 mg/m2 (d 1, 22, 43) and dose-escalating (106, 106, 106, 106 pfu/mL [cohort 1]; 106, 107, 107, 107 [cohort 2]; 106, 108, 108, 108 [cohort 3]) OncoVEXGM-CSF by intratumoral injection (d 1, 22, 43, 64). Pts underwent neck dissection 6–10 weeks after CRT. Primary endpoints were safety and recommended dose/schedule for future study. Secondary endpoints were anti-tumor activity, viral replication and HSV antibody levels. Results: 17 pts were treated, 9 at the top dose (15 males, median 58 years). DLT and MTD were not reached. There were no delays to CRT delivery. 13 pts had PR or CR by CT, 5 pts achieving rapid CR following only 2 or 3 viral doses. Pathological CR was observed in 94% of pts at neck dissection. Transient low level injection site viral shedding was seen in 3 pts. HSV was detected in injected and adjacent uninjected tumors by qPCR and immunohistochemistry, including at levels higher than the input dose, indicating replication. All seronegative pts seroconverted. 11 of 17 (65%) pts remain in remission at median follow-up of 23 months. No pts had local relapse, 1 pt had a new primary tumor, 3 pts distant metastatic disease, 1 pt intercurrent disease, 1 pt lost to follow up. Conclusions: OncoVEXGM-CSF combined with cisplatin-based CRT is well tolerated in pts with SCCHN. Viral replication was confirmed. Long-term locoregional control was achieved in 100% of pts, 65% of pts remaining in complete remission. Further study is warranted. [Table: see text]
Evaluation of the correlation of baseline blood pressure (BP) and plasma renin activity (PRA) with bevacizumab (B)-mediated hypertension in patients with early-stage breast cancer
Authors: Dickler M. N. , McArthur H. L. , Nulsen B. , Patil S. , Sealey J. , Laragh J. , Merali C. , Steingart R. , Hudis C. , Rugo H. 
Published: August 2020

602 Background: Although hypertension (HTN) develops in 20–30% of bevacizumab (B)-treated cancer patients, no accurate clinical predictors of B-mediated HTN have been identified. We evaluated baseline blood pressure (BP) and plasma renin activity (PRA) as potential predictors of B-mediated HTN among breast cancer patients enrolled in an adjuvant chemotherapy-B study. Methods: In this phase II study, B was administered concurrently (10 mg/kg IV q2wk x 8) with pegfilgrastim-supported chemotherapy (AC at 60/600 mg/m2 q2wk x4 then nab-paclitaxel at 260 mg/m2 q2wk x4) and continued at 15 mg/kg q3wk thereafter for a total one year of B therapy. The primary endpoint was cardiac safety. A secondary endpoint was the prospective exploration of PRA as a predictor of HTN. Patients with baseline BP >150/100 mmHg were excluded from the study. Peripheral blood for PRA was collected at baseline, week 8, week 16 and every 3 months during B administration. In this preliminary analysis, baseline data was available for 65 of the 80 enrolled patients. Baseline BP and PRA values for those who did and did not develop grade 2–4 HTN were evaluated by Wilcoxon rank sum test. Results: The baseline characteristic medians are: age 45y (27–75), baseline diastolic BP 70 mmHg (52–95), baseline systolic BP 120 mmHg (90–146), and number of B cycles administered 20 (1–21). Twenty-one patients (32%) developed grade 2–4 HTN. Median diastolic and systolic BP among patients with grade 2–4 HTN was 78 and 124 mmHg, respectively, versus 70 and 115.5 mm Hg, respectively, among patients without grade 2–4 HTN (p = 0.0256 and p = 0.0228). There was no significant association between baseline PRA values and the development of grade 2–4 HTN versus not (p = 0.2917). Conclusions: At the time of this preliminary analysis, both baseline diastolic and systolic BP appear to positively predict the development of B-mediated grade 2–4 HTN while baseline PRA does not. Studies exploring the relationship between serial PRAs and the development of HTN for all study participants are ongoing. [Table: see text]
Serum biomarkers as predictors of clinical outcome after cetuximab-based therapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Ferris R. L. , Feinstein T. , Grandis J. , Johnson R. , Branstetter B. , Gooding W. , Argiris A. 
Published: August 2020

6035 Background: We correlated a panel of serum cytokines and growth factors with antitumor activity in patients (pts) with locally advanced SCCHN treated with cetuximab-based therapy. We have shown that similar biomarkers may be promising for the early detection of SCCHN (Linkov, Can Epi Biomarkers 2007). Methods: We used multi-analyte biomarker profiling for measurement of multiple serum biomarkers (Luminex Corp., Austin, TX). 39 pts with stage III-IVB SCCHN were treated with cisplatin, docetaxel, and cetuximab (TPE) for 3 cycles followed by radiotherapy, cisplatin, and cetuximab (XPE) and then maintenance cetuximab (Argiris, ASCO 2008, A6002). 31 cytokines and growth factors were measured before and after 3 cycles (9 weeks) of induction TPE. Clinical results were correlated with biomarkers, including 23 pts with PET response. Results: 31 pts had baseline biomarkers and 25 paired samples, pre- and post-TPE. Median follow-up was 22 months. Median age 54 years (21–74); male: 27; stage IV: 29; primary site: oropharynx, 16; larynx, 4; hypopharynx, 3, nasopharynx, 3; oral cavity, 3; and unknown, 2. Eight analytes changed significantly after induction. Adjusting p values for false discovery, the following analytes retain a p <0.05: MCP1c, IP-10, Leptin, IL-5, Eotaxin, IL-6, GCSF, CXCL5. In 23 pts with PET response assessment, low vascular endothelial growth factor (VEGF) levels or low IL-6 levels at baseline may be associated with complete response: 4/5 pts with low baseline VEGF (<20.9 pg/ml) had a complete response by PET vs 1/18 pts with high baseline VEGF. Of 31 pts, 9 have progressed. Among tests of association of the 31 analytes and progression-free survival (PFS), VEGF was the only one with a raw p value <.05 (p = .027), although the adjusted p value was not significant. A decrease in VEGF with treatment had a weak but not statistically significant association with longer PFS. Conclusions: Baseline serum biomarkers and in particular, VEGF and IL-6, were identified as potentially useful predictive markers of cetuximab-based therapy. Due to the small sample size and multiple testing, these biomarkers need to be validated in a larger study in SCCHN specifically powered for biomarker associations. No significant financial relationships to disclose.
Identifying head and neck cancer patients at risk for high symptom burden during treatment
Authors: Rosenthal D. I. , Mendoza T. , Cleeland C. 
Published: August 2020

6066 Background: Treatment for head and neck cancer (HNC) is well known to be associated with high levels of toxicity and symptom burden, but patients vary in the severity of treatment related symptom burden. The pre-treatment identification of patient characteristics most at risk for high treatment related symptom levels would be helpful for clinical and trial symptom intervention planning. Methods: 134 patients with HNC participated in the study. Patients completed the M. D. Anderson Symptom Assessment Inventory - Head and Neck module (MDASI-HN) prior to radiotherapy (RT) or chemoradiotherapy (CRT) and again six weeks after treatment began. Cluster analysis was used to identify those who were highly symptomatic due to their disease prior to treatment and those who became highly symptomatic due to treatment. We used validated MDASI-HN score ranges to define symptom severity with scores 5–6 defined as ‘moderate‘ and 7 or more as ‘severe.’ Logistic regression was used to determine which baseline symptoms may predict group membership of highly symptomatic patients at the end of therapy. Results: 18% (22/120) of HNC patients were symptomatic prior to therapy. This subset of patients reported moderate levels of pain, fatigue, sleep disturbance, feeling sad and emotional distress. At six weeks after beginning treatment, 59% (73/124) of patients were highly symptomatic. The cluster of symptoms at this point included moderate levels of pain, fatigue, nausea, mouth sores and excessive mucus and severe levels of poor appetite, dry mouth, difficulty chewing and loss of taste for food. Approximately 54% (50/92) of patients who were not symptomatic at the beginning of treatment became symptomatic at the end of treatment. Patients with moderate to severe pain before beginning treatment are 4 times more likely to be severely symptomatic at the end of treatment (p < 0.009). Conclusions: As expected, only a minority of patients with HNC were highly symptomatic prior to therapy, while the majority of patients had high levels of symptoms toward the end of therapy. Patients with moderate to severe pain before beginning treatment are more likely to be have greater symptom burden at the end of treatment, so may benefit from more intensive symptom interventions. No significant financial relationships to disclose.