bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical activity of imatinib mesylate in combination with docetaxel in patients with advanced, platinum-resistant ovarian cancer—Hoosier Oncology Group GYN03–62
Authors: Matei D. , Emerson R. E. , Menning N. , Schilder J. , McClean J. , Sutton G. , Stephens D. , Whalen C. , Baldridge L. , Moore D. 
Published: March 2020

5091 Background: Ovarian tumors harborc-Kit and PDGF receptors. We showed in an in-vitro model that Imatinib (G) inhibits the growth of ovarian cancer cells. We hypothesized that G in combination with chemotherapy inhibits the growth of ovarian tumors. Data from a phase II clinical trial utilizing G in combination with Docetaxel (D) in patients with advanced ovarian cancer (OC) are presented. Methods: This was an open label, one stage, multi-center phase II clinical trial. Planned sample size was 23. Patients with relapsed, platinum-resistant or refractory OC expressing PDGFR or c-kit were eligible. PDGFR and c-kit expression was assessed prior to enrollment by IHC using archival tumor tissue. G was administered at 600mg/d continuously and D was given weekly (30mg/m2) for 4 weeks, with 2 weeks break. Each cycle was 6 weeks, with a maximum of 6 cycles allowed. Tumor assessments were obtained after 2, 4 and 6 cycles. Response rate by RECIST was the primary endpoint. Results: 34 patients were screened. 17 tumors were c-kit + and 25 were PDGFRα +. 23 patients were enrolled. Of those, 4 patients had c-kit+/PDGFR- tumors, 12 were PDGFR+/c-kit- and 7 were c-kit+/PDGFR+. Median age was 55 (range 33–76) and median PS was 0 (range 0–2). Median number of prior treatments was 3 (range 1–9). Efficacy and toxicity data are available for 20 and 14 patients, respectively. Based on RECIST, there were 3 patients with PR and 3 patients with SD lasting at least 12 weeks. Of these 6 patients, 2 pts were c-kit+, 2 were PDGFR+ and 2 were PDGFR and c-kit+. All 6 patients had carboplatin and taxane resistant disease. Grade 3–4 toxicities were: neutropenia (2), thrombocytopenia (1), fatigue (1), dehydration (1), constipation (1), cardiac ischemia (1), nausea/vomiting (2), urinary frequency (1). Other G1–2 toxicities were: N/V (9), diarrhea (7), fatigue (8), mucositis (4), anemia (4), hypocalcemia (5), rash (6), anorexia (7), edema (5), hemolysis (1), non-neutropenic infections (7). Additional data will be available in May 2006. Conclusions: The combination G+D is tolerated well. Clinical activity consisted of 3 PRs (15% response rate) and 3 SD > 3 months in pts with heavily pre-treated, platinum resistant OC expressing c-kit or PDGFRα. [Table: see text]
End of life treatments and events in ovarian cancer: A comparison of short versus long-term outcomes
Authors: Von Gruenigen V. E. , Daly B. , Frasure H. , Hutchins J. , Green A. 
Published: March 2020

5096 Background: To identify the aggressiveness of treatment and events in ovarian cancer patients during the last year of life based on survival time. Methods: Patient charts of deceased epithelial ovarian cancer patients were retrospectively reviewed from 2000–2005. All patients included had debulking surgery and received adjuvant chemotherapy. Patients were separated into groups based on survival quartiles. Aggressiveness of care was measured by chemotherapy regimens, ER visits and hospitalizations. Significant clinical events (SCE) were defined as ascites, bowel obstruction, and pleural effusion. Comparison of quartiles was done using chi-square and t-test statistic. Multiple regression analysis was done using survival duration as a dependent variable. Results: 97 patients with epithelial ovarian cancer were reviewed. There was no difference in patterns of hospitalizations and SCE between the top and bottom survival quartiles. Patients with a shorter survival time received more chemotherapy during their last 3 months of life and had increased overall aggressiveness of care measures (Table). In patients who had a remission, regression analysis revealed length of initial remission time was significant in predicting survival (p < 0.01). Time to 2nd relapse was also significant in predicting survival time (p < 0.01). Number of SCE during the last year of life events trended for predicting survival (p = 0.10). Conclusions: Duration of ovarian cancer remission is predictive of survival. Those patients with a short trajectory of disease receive more aggressive care, chemotherapy at the end of life, less hospice care; however, they die similarly to those with longer survival duration. Those patients with short remissions and / or SCE during recurrence should receive less aggressive care at the end-of-life. [Table: see text] No significant financial relationships to disclose.
HER2 predicts benefit from adjuvant paclitaxel after AC in node-positive breast cancer: CALGB 9344
Authors: Hayes D. F. , Thor A. , Dressler L. , Weaver D. , Broadwater G. , Goldstein L. , Martino S. , Ingle J. , Henderson I. C. , Berry D. 
Published: March 2020

510 Background: CALGB 9344 showed 4 cycles of paclitaxel (T) after 4 cycles of doxorubicin/cyclophosphamide (AC) improved disease-free (DFS) and overall survival (OS) compared to 4 cycles of AC. Higher dose of A had no benefit (Henderson JCO ’03). Prior studies suggest HER2 is associated with benefit from standard vs low dose of C&A (Dressler JCO ’05). We hypothesized that HER2 might predict benefit from higher dose of A or from T, and that HER2 might refine the observed negative interaction of T with estrogen receptor (ER). Methods: 3121 node + women in CALGB 9344 received 4 q3wk cycles of AC (A: 60, 75, or 90 mg/m2) and then 4 cycles of T (175 mg/m2 q3wk) or no T. Blocks were collected from ∼2800 subjects. 2 sets of 750 patients each were randomly selected from these cases: Set 1 to develop hypotheses; Set 2 for validation. Tissue specimens were available from 643 (set1) and 679 (set2) cases (20% & 22% total enrolled in 9344 respectively). HER2 was evaluated by FISH and by IHC (by antibody cb11 and by Herceptest). Statistical analyses used Cox proportional hazards models, including interaction terms, and Kaplan-Meier estimates for comparing 5-yr DFS by treatment group. Results: In Set 1, all 3 assays suggested that T improved DFS for HER2+ but not for HER2-. For this single set the interaction was not statistically significant. There appeared to be an interaction of HER2, T and ER. IHC using cb11 was applied to Set 2, revealing nearly identical results. In the two sets combined (n=1322), the interaction between HER2 and T was statistically significant (p=0.013). The 3-way interaction of HER2, ER and T was hypothesis-generating and not tested statistically. Differences in 5-yr DFS rates (95% CI) for T vs. no T by HER2 and ER (both sets combined) There was no interaction between HER2 and dose of A. Conclusions: These results suggest that the benefit of adding T to AC is greater for HER2+ tumors, even if ER+, while T was of no apparent benefit in the ER+, HER2- group. Further validation is needed from remaining cases in 9344 and from other trials involving T. [Table: see text] [Table: see text]
Survival benefit of switching to anastrozole after 2 years’ treatment with tamoxifen versus continued tamoxifen therapy: The ARNO 95 study
Authors: Kaufmann M. , Jonat W. , Hilfrich J. , Eidtmann H. , Gademann G. , Zuna I. , Von Minckwitz G. 
Published: March 2020

547 Background: Initial adjuvant treatment with anastrozole has significant efficacy and tolerability advantages over tamoxifen in postmenopausal women with hormone-sensitive early breast cancer (EBC) (ATAC Trialists’ Group. Lancet 2005; 365: 60–62). The ARNO 95 study evaluated prospectively switching to anastrozole from tamoxifen after 2 years, compared with continuing tamoxifen therapy. Here, we present an interim efficacy and safety analysis. Methods: This was a prospective, randomized, open-label study conducted in 54 centers in Germany. Postmenopausal women (≤75 years) with hormone receptor-positive, invasive EBC, who had received 2 years of adjuvant tamoxifen without recurrence, were randomized to switch to anastrozole (1 mg/day) or continue on tamoxifen (20 or 30 mg/day) for a further 3 years. No adjuvant chemotherapy was given. The primary end point was disease-free survival (DFS; time to earliest occurrence of local or distant recurrence, new primary breast cancer, or death from any cause); secondary end points included overall survival (OS), safety, and tolerability. Data were analyzed using a log-rank test; a second analysis used a Cox proportional hazards model with covariates of age, tumor size, nodal status, grade, and type of surgery. Results: Overall, 979 patients (mean age 60 years; 74% node-negative; 97% hormone receptor-positive) were enrolled, 489 were randomized to switch to anastrozole, with 490 continuing on tamoxifen. Median follow-up was 30.1 months. Switching to anastrozole significantly improved DFS and OS compared with continuing on tamoxifen ( Table ). Fewer patients who switched to anastrozole reported serious adverse events (22.7%) compared with those who remained on tamoxifen (30.8%). Conclusions: Switching endocrine treatment improved DFS and OS in this well-defined population. Postmenopausal women with hormone-sensitive EBC who have already received 2 years’ adjuvant tamoxifen therapy should be switched to anastrozole. [Table: see text] [Table: see text]
High gene copy number of epidermal growth factor receptor by fluorescence in situ hybridization is frequent in head and neck squamous cell carcinomas and associates with worse recurrence-free survival
Authors: Chung C. H. , Ely K. , Carter J. , McGavran L. , Varella-Garcia M. , Nanney L. , Yi Y. , Slebos R. J. , Yarbrough W. , Hirsch F. R. 
Published: March 2020

5502 Background: Epidermal growth factor receptor (EGFR) is expressed in 90–95% of head and neck squamous cell carcinoma (HNSCC). High EGFR gene copy number and activating mutations correlate with response and survival in lung cancer upon the treatment with EGFR tyrosine kinase inhibitors, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors and provide a rationale for combination therapy. Methods: Tumor samples were obtained from 47 patients and analyzed for increased EGFR copy numbers by fluorescence in situ hybridization (FISH) (Vysis/Abbot) (N = 47), by immunohistochemistry (IHC) using antibodies against EGFR, phospho-EGFR (Tyr1173) and phospho-AKT (Ser473) (N = 31), for activating mutations in EGFR exons 18, 19 and 21 (N = 29), and for gene expression using Affymetrix Human 133U Plus 2.0 GeneChip (N = 18). Results from these assessments were tested for associations with patient characteristics and clinical endpoints. Univariate analysis was performed to test for differences in recurrence-free survival (RFS) and overall survival. Results: Twenty-six (63%) of 41 samples with FISH result demonstrated EGFR high polysomy and/or gene amplification (FISH+). The FISH(+) group did not differ from the FISH(−) group with regard to age, sex, race, tumor grade and site, disease stage, total EGFR, phospho-EGFR, or phospho-AKT, although the total EGFR protein score was close to significance (p = 0.10, Chi2-test for trend). The FISH(+) were associated with worse RFS, although this association did not reach significance (p = 0.057, Wilcoxon test). No activating EGFR point mutations were found. Using the FISH results as a supervising parameter, microarray data was interrogated and expression of genes involved in wnt signalling, cell motility, G-protein regulation and epithelial-mesenchymal transition pathways were found to be enhanced in the FISH(+) group (FDR <25%). Conclusions: High gene copy number of EGFR by FISH is frequent in HNSCC and may be a poor prognosticator. This data suggests that FISH(+) may be a marker of clinical benefit upon EGFR inhibition in HNSCC and further investigation is indicated. [Table: see text]
Postoperative concurrent radiochemotherapy versus radiotherapy in high-risk SCCA of the head and neck: Results of the German phase III trial ARO 96–3
Authors: Fietkau R. , Lautenschläger C. , Sauer R. , Dunst J. , Becker A. , Baumann M. , Wendt T. , Grüschow K. , Hess C. , Budach V. , Iro H. 
Published: March 2020

5507 Background: Despite resection and postoperative irradiation high-risk (3 or more involved lymph nodes, extra-capsular disease and/or microscopically involved mucosal margins of resection) squamous cell carcinomas (SCCAs) of the head and neck frequently recur in the tumor bed. Postoperatively radiochemotherapy (RCT) with cis-Platin (CDDP)/5-FU versus radiotherapy (RT) alone was compared in a randomized trial. Methods: Between 5/97 and 12/04, 440 patients who had high-risk SCCAs of the head and neck were enrolled in this prospectively randomized phase III trial. Following resection and neck dissection, 214 patients were randomly assigned to RT (66 Gy/33 Fx/6.6 weeks) and 226 patients to identical RT plus CDDP (20 mg/m2 on day 1–5, 29–33) and 5-FU (600 mg/m2 on day 1–5, 29–33). Results: The 5 year local-regional control rate is 72.2 ± 3.7% following RT and 88.6 ± 2.4% for the RCT group (p = 0.00259; 5-year progression free survival 50.1 ± 4.0% and 62.4 ± 4.4% (p = 0.024) and 5-year overall survival 48.6 ± 4.4% vs. 58.1 ± 4.6% (p = 0.11). There was no difference in the 5 year incidence of distant metastases (19.3 ± 3.6% vs 25.5 ± 4.6%; p = 0.45). The incidence of grade 3+ acute toxicity was higher during RCT: mucositis 12.6% vs. 20.8% (p = 0.04), leucopenia 0% vs. 4.4% (p = 0.007). Conclusions: Acute toxicity is increased to an acceptable level by RCT. Postoperative RCT compared to RT improves locoregional control and progression free survival; thus survival as a trend is improved by 10% after 5 years. Supported by Deutsche Krebshilfe 70–2140. No significant financial relationships to disclose.
Epidemiology of nasopharyngeal carcinoma (NPC) in California: Survival advantage of Chinese WHO Type 1 NPC patients resulted in Asian ethnicity as an independent and favorable prognostic factor of survival for NPC patients as a whole and for patients with the WHO histologic type 1
Authors: Ou S. I. , Zell J. A. , Ziogas A. , Anton-Culver H. 
Published: March 2020

5514 Background: We have previously shown that Chinese race is an independent and favorable prognostic factor in NPC survival. We expanded our study to investigate whether Asian ethnicity has the same favorable survival characteristics and if there is a survival difference between Chinese and non-Chinese Asians. Methods: 1,657 newly diagnosed NPC patients from 1992 to 2002 were analysed from the population-based California Cancer Registry. Five year survival rate estimates and Kaplan-Meier curves were calculated. Cox proportional ratios were used to identify independent prognostic factor for survival. Results: The 5-year survival rate of Asian NPC patients was improved compared to non-Asian patients (62% vs 47%; P < .0001). By multivariate analyses, early age of diagnosis, localized stage at presentation (vs distant, HR = 0.41; P < .0001), WHO Type 3 histology (vs Type 1; HR = 0.64; P < .0001), socio-economic status (highest vs lowest quartile; HR = 0.71; P = .0012), use of radiation (vs none; HR = 0.55; P < .0001), and Asian ethnicity (vs Caucasian; HR = 0.82; P = .016) were associated with improved survival. Chinese composed the majority of the Asian ethnicity (49.1%) followed by Filipino (21.2%) and Vietnamese (14.9%). The 5-year survival rate of Chinese was better than non-Chinese Asians (67% vs 56%; P = .0005). When Asian ethnicity was analyzed separately as Chinese and non-Chinese, Chinese retained an overall favorable prognosis (HR = 0.72; P = .0016) whereas non-Chinese Asians did not (HR = 0.91; P = .34). Within each NPC WHO histologic type, early age of diagnosis, localized stage at presentation, and use of radiation were favorable prognostic factors. Chinese (HR = 0.62; P = .0006) but not non-Chinese Asian ethnicity (HR = 0.78; P = .053) was an additional favorable prognostic factor within WHO histologic Type 1. Conclusions: The significant survival advantage of Chinese WHO Type 1 NPC patients resulted in Asian ethnicity being an independent and favorable prognostic factor for survival in NPC. This observation may reflect underlying genetic difference among different racial groups with NPC WHO Type 1. No significant financial relationships to disclose.
A randomized phase II study of BMS-247550 (ixabepilone) given daily x 5 days every 3 weeks or weekly in patients with metastatic or recurrent squamous cell cancer of the head and neck
Authors: Burtness B. , Goldwasser M. A. , Axelrod R. , Argiris A. , Forastiere A. A. 
Published: March 2020

5532 Background: Ixabepilone is a novel tubulin-polymerizing agent, with potential activity in SCCHN. Methods: Patients (pts) were eligible who had incurable, measurable SCCHN. ≤ 2 prior regimens for metastatic/recurrent disease were permitted, including taxanes. ECOG PS 0 or 1, ANC ≥ 1500/ml and adequate renal/hepatic function were required. Pts were randomized to ixabepilone 6 mg/m2/d 60 minute (min) infusion x 5 days (d) q 21 d [Arm A], or 20 mg/m2 60 min infusion d1, 8, and 15 q 28 d [Arm B], with diphenhydramine premedication. Tumor assessment was q 6 weeks. Each arm accrued taxane-naive (Tax-N) and -exposed (Tax-E) patients as separate strata, in a 2-stage design. The primary endpoint was response.16 pts entered each group in the first stage. If 1 response was observed in any group, it continued to 32 pts. Results: 85 eligible pts entered. Male 69, ECOG PS (1) 58, metastatic disease 66. 15 Tax-E and 17 Tax-N eligible pts entered stage 1 of Arm A. There were no responses with this dose and schedule. 35 eligible Tax-N pts were accrued to Arm B and 5 had partial responses (14.3%, 90% CI 5.9%,28.2%), 11 stable and 9 progressive disease. 10 in this group were inevaluable (5 died before restaging, 2 were never treated).18 eligible Tax-E pts entered Arm B and none responded. On Arm A, 2/16 Tax-N pts developed grade (gd) 3/4 anemia (13%), and 4/16 (25%) developed gd 3 fatigue. Other gd 3/4 toxicities occurred in < 8% of pts on Arm A. On Arm B, 9/33 (27%) Tax-N pts experienced gd 3/4 leukopenia, 3/33 (9%) gd 3/4 anemia 7 gd 3/4 fatigue (21%), 4 gd 3 nausea (12%), 9 (27%) gd 3 sensory and 2 (6%) gd 3 motor neuropathy. 2/21 Tax-E pts on Arm B experienced gd 4 neutropenia (10%), 6 gd 3 fatigue (29%), 3 gd 3 motor (14%) and 2 gd 3 sensory neuropathy (10%). Median follow up for eligible pts is 31.5 months (mo). 75 have died. Median survival for Arm A Tax-N is 5.62 mo (CI 4.0, 10.0); for Arm A Tax-E is 6.5 mo (CI 2.7, 8.8); for Arm B Tax-N is 7.8 mo (CI 3.3, 8.9) and for Arm B Tax-E is 6.5 mo (CI 2.0, 11.3). Conclusions: Ixabepilone 20 mg/m2 d1,8,15 q 28 d is active and tolerable in taxane-naive pts with metastatic/recurrent SCCHN. A high incidence of motor and sensory gd 3 neuropathy results at this dose and schedule in patients with previous taxane exposure. [Table: see text]
Oral mucositis (OM) related morbidity and resource utilization in a prospective study of head and neck cancer (HNC) patients
Authors: Isitt J. , Murphy B. A. , Beaumont J. L. , Garden A. S. , Gwede C. K. , Trotti A. , Meredith R. F. , Epstein J. B. , Le Q. , Brizel D. M. 
Published: March 2020

5539 Background: Few studies have reported the burden of oropharyngeal mucositis (OM) as well as the downstream resource consumption and risk of complications due to OM following standard therapy in head and neck cancer patients. This study was a prospective, multi-center, single-arm observational study of patients receiving radiation with or without chemotherapy for head and neck cancer. Methods: Over a 6-week period, the severity and impact of OM were assessed 5 times with the oral mucositis weekly questionnaire (OMWQ-HN) and patient resource use was collected bi-weekly. Seventy-five patients were enrolled from 6 centers in the United States. Hospitalization costs are reported from the Healthcare Utilization Project Nationwide Inpatient Sample (HUPNIS). Results: Sixty-seven percent (95% CI: 55%–77%) of the patients received concurrent chemoradiation. Seventy-six percent (95% CI: 65%–85%) of patients reported severe mouth and throat soreness. Eighty-five percent (95% CI: 75%-92%) were prescribed opioid analgesics. Mouth pain and throat pain accounted for 78% (95% CI: 68%–86%) of opioid uses. During weeks 1 and 2, 38% (95% CI: 26%-50%) of patients reported severe difficulty swallowing (59% by week 6); 67% (95% CI: 46%-83%) of these patients were taking opioids (84% by week 6). Over half of the patients (38/75; 51% [95% CI: 39%–62%]) had a feeding tube placed. Twenty-eight patients (37% [95% CI: 26%–49%]) were hospitalized, 30% (95% CI: 16%–49%) of hospitalizations were considered related to mucositis. Mean length of stay was 4.9 days (range: 1–16, SE: 0.72). National average cost for a 5-day hospitalization during this study period was approximately $23,000 (SE: $565.00 [HUPNIS]). Conclusions: Mucositis is a frequent, severe, and costly complication of treatment for head and neck cancer. Effective interventions may not only relieve patient suffering but also reduce healthcare consumption and downstream costs. [Table: see text]
Cetuximab (C225) in recurrent and/or metastatic salivary gland carcinomas (RMSGCs): A monoinstitutional phase II study
Authors: Licitra L. F. , Locati L. D. , Potepan P. , Crippa F. , Bossi P. , Bergamini C. , Rinaldi G. , Liberatoscioli C. , Perrone F. , Losa M. , Pilotti S. 
Published: March 2020

5547 Background: EGFR is expressed in 70% of salivary gland carcinomas (SGC). Investigations of anti EGFR treatment seems rational. Aim: To assess activity of C225 in patients with RMSGCs in terms of clinical benefit (CB), defined as occurrence of objective response (CR or PR) or stable disease (SD) for at least 6 months. To correlate treatment outcome with skin toxicity degree and EGFR analysis. Methods: One prior chemotherapy regimen was allowed, except for pts with adenoid cystic carcinoma (ACC) and acinic cell carcinoma for whom 2 lines were allowed. Prior exposure to targeted treatment was not allowed. C225 (Erbitux) was administered iv weekly at 400 mg/mq followed by 250 mg/mq until disease progression, major toxicity or voluntary discontinuation. MRI or CT and PET scan were performed every 6 weeks q4, and q12 thereafter. RECIST response criteria and CTC 3.0. were adopted. Results: From April to December 2005, 30 RMSGCs pts (20 F/10 M; median age 50 yrs), 50% with major SGC, were enrolled. Histotypes were: 23 ACC; 2 mucoepidermoid; 3 myoephitelial; 1 cystadenocarcinoma and 1 acinic cell carcinoma. Thirteen pts (43%) received prior chemotherapy. Localregional (LR) and metastatic (M) disease was present in 13 cases, M in 12, and LR in 5. A median number of 11 drug administration (range 2–31) was given. G2 skin toxicity was recorded in 24 cases. G2 fatigue in 2. At a median FU of 6 months (range 0–8), 2 pts died of PD. Of 22 pts evaluable for response with ≥ 3 months of potential FU, there were 11 SD, 9 PD, while 2 pts refused to continue after 1 months. Currently, 7 of these pts are progression-free at ≥ than 6 months, qualifying for CB definition according to study protocol. Preliminary EGFR analysis showed a high or intermediate expression score in 5 (3 ACC, 1 acinic cell, 1 cistoadenocarcinoma) out of 7 cases, no gene amplification nor chromosome 7 polisomy were found in 3 of 3 analysed ACC. PET results are under evaluation. Conclusions: Hints of activity of C225 in RMSGCs were observed. The early analysis for the CB rate in 23 pts is planned for April 2006, when all of them will have a potential follow-up of ≥ 6 months, and results thereof will be reported. [Table: see text]