bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change in patient weight during platinum/paclitaxel-based chemotherapy for ovarian cancer: A Gynecologic Oncology Group study
Authors: Hess L. M. , Tian C. , Barakat R. , Ozols R. , Alberts D. 
Published: March 2020

5073 Background: Platinum/paclitaxel (P)-based chemotherapy is current treatment (tx) for advanced epithelial ovarian cancer (EOC). Previous studies suggest this regimen may induce weight change, which is a surrogate for body reaction to tx and may predict quality of life and clinical outcomes. We sought to explore the association between weight change during treatment and survival. Methods: A retrospective data review was conducted of 792 patients who participated in a Gynecologic Oncology Group (GOG) phase III randomized treatment trial (GOG 158) using cisplatin (Cis)/P vs carboplatin (Carbo)/P in optimal stage III EOC. Pretreatment body mass index (BMI) was calculated based on patient height and weight following surgery. Weight change during tx was defined as the ratio of body weight at completion of protocol therapy to pretreatment body weight. Progression-free survival (PFS) and overall survival (OS), classified by BMI or relative weight change, were estimated by Kaplan-Meier, and the associations between BMI, relative weight change and PFS and OS were assessed using Cox model controlled for known prognostic variables. Results: The median BMI was 24.9. There was no significant difference in PFS or OS related to BMI; however, there was a significant relationship between median OS and weight change as follows: >5% decrease = 48.0 months; 0–5% decrease = 49.3 months; 0–5% increase = 61.1 months; and >5% increase = 68.2 months (p = 0.006). The relative risk of death increased by 7% for each 5% decrease in body weight (HR = 0.93, 95% CI = 0.88–0.99; p = 0.013) adjusted for covariates. Results suggest more evident weight loss in the Cis/P arm than the Carbo/P arm during the first cycle of tx (−2.2 kg vs. −1.2 kg), and decreased weight was more likely to return to pretreatment level in the Carbo/P arm. Conclusions: Loss of body weight, but not BMI, during platinum/P-based chemotherapy is an indicator for poor OS in EOC patients. Cis/P may be associated with more weight loss compared to Carbo/P. This exploratory study supports the development of treatment strategies that minimize weight loss-producing toxicities to improve outcomes in this patient population. No significant financial relationships to disclose.
Phase II trial of GM-CSF in women with asymptomatic müllerian cancer
Authors: Roche M. , Matulonis U. , Krasner C. , Penson R. , Horowitz N. , Berkenblit A. , Findley M. , Lee J. , Horick N. , Seiden M. V. 
Published: March 2020

5081 Background: GM-CSF is a recombinant human cytokine, which increases the proliferation of granulocytes and monocytes. Experience with this agent, including adjuvant studies in melanoma, vaccine-based studies using autologous tumor vaccines that secrete human GM-CSF, and studies in prostate cancer using GM-CSF have all suggested that GM-CSF might provide anti-tumor activity in a subset of cancer patients. Methods: Open label phase II study performed in asymptomatic patients with recurrent mullerian malignancy without an indication for immediate systemic chemotherapy. Patients could have measurable or evaluable disease (defined as CA-125 >35 U/ml or 2 successively rising values with the most recent 3x the nadir value.) GM-CSF 250 mcg/m2 was administered subcutaneously on days 1–14 of a 28-day cycle. Monthly follow-up included interim history, physical exam and CA-125, with radiologic evaluation q 3 months. Results: Enrollment to this cohort is complete. Thirty-five women with a median age of 60 were enrolled; data are available on 33:30 women with ovarian and 3 with primary peritoneal cancers. To date 31 women are evaluable for response. Best overall response of patients who have completed the study includes 6 patients with stable disease (18%). Median time to treatment termination (TTT) was 76 days. Four patients remain on study, 2 with SD >6 months. Toxicity was generally mild, including injection site reaction, fatigue, and bone pain, however 2 patients experienced excessive toxicity and withdrew consent. There were 3 bowel obstructions thought related to disease but contribution of drug could not be ruled out. After 14 days of GM-CSF, CA-125 dropped in 23 of 33 women (70%) from their baseline on study value (median change -23%, range −48 to +158%). The magnitude of CA-125 drop during the first two weeks of therapy was significantly and positively correlated with day 15 WBC (p = 0.04.) Conclusions: GM-CSF is well tolerated and frequently associated with a decline in CA-125 that is correlated with leukocytosis. Although median TTT for the entire group is modest, a subset of women have had prolonged stable disease. Strategies to maintain and titrate leukocytosis are now being explored in a separate cohort. No significant financial relationships to disclose.
Phase II study of sorafenib (BAY 43–9006) in combination with gemcitabine in recurrent epithelial ovarian cancer: A PMH phase II consortium trial
Authors: Welch S. , Hirte H. , Schilder R. J. , Elit L. , Townsley C. , Tinker L. , Pond G. , Afinec A. , Wright J. J. , Oza A. M. 
Published: March 2020

5084 Background: Sorafenib (BAY 43–9006; SOR) is a novel multi-targeted kinase inhibitor that targets the RAF/MEK/ERK signaling pathway, vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor and flt-3. VEGFR is over-expressed in human ovarian tumors and this is associated with poor prognosis. Gemcitabine (GEM) is known to have single-agent activity in recurrent ovarian cancer (OC). A recent phase I study of GEM/SOR has demonstrated manageable toxicity and some objective responses in recurrent OC patients. We have designed a phase II trial to evaluate the efficacy of this novel combination in patients with recurrent OC. Methods: A two-stage, phase II clinical trial is underway for women with recurrent or refractory OC. Eligible patients may have received up to 2 prior lines of chemotherapy following recurrence, but must be GEM-naive. The treatment consists of SOR, 400mg PO bid continuously, in combination with GEM, IV weekly, 1000 mg/m2. Cycle 1 is an extended cycle of 7 weeks of GEM followed by a 1-week break. GEM is administered weekly for the first 3 weeks of each subsequent 4-week cycle. The primary endpoint is objective response rate, with response evaluated every 8 weeks. Results: 26 patients have been enrolled at 3 centers. 84 cycles have been administered (median 3; range 1–10). Median age was 57 (range: 37–77). 42% were ECOG PS 0 and 58% were PS 1. Of 18 patients evaluable for objective response, 1 patient had a confirmed PR by RECIST criteria and 5 patients had a confirmed PR by CA-125 criteria, yielding a combined RR of 33% in evaluable patients (RR by ITT = 23%). An additional 10 patients had SD. The median time to progression is 7.6 months (95% CI: 5.6-NA). 7 patients are inevaluable for objective response due to the following in cycle 1: withdrawal of consent (3), toxicity (2), and clinical PD (2). 1 patient on-study is yet to have a response evaluation. Grade 3 or 4 toxicities seen in more than 2 patients include: lymphopenia (8), thrombocytopenia (6), hypertension (3), hand-foot syndrome (3), pain (3), neutropenia (3) and hypokalemia (3). Conclusions: The preliminary results show encouraging activity with tolerable toxicity. This trial continues to accrue into a second stage. No significant financial relationships to disclose.
A phase II study of oral gimatecan (ST1481) in women with progressing or recurring advanced epithelial ovarian, fallopian tube and peritoneal cancers
Authors: Pecorelli S. , Ray-Coquard I. , Colombo N. , Katsaros D. , Lhomme C. , Lissoni A. , Vermorken J. B. , Du Bois A. , Poveda A. , Frigerio L. 
Published: March 2020

5088 Background: Gimatecan, a new camptothecin derivative, is a potent topoisomerase I inhibitor, active by oral route. Methods: A multicenter two stage Simon design phase II study was performed to evaluate the single agent antitumor activity of gimatecan. Secondary objectives were safety, time to event/time related parameters, and translational medicine evaluations. Women with advanced epithelial ovarian, fallopian tube or peritoneal cancer who had progressed or recurred after prior treatment with platinum and taxanes, had a progression-free interval from last platinum-based therapy < 12 months, had measurable disease by RECIST or assessable by CA 125 (GCIG criteria) and a ECOG performance status ≤ 1 were eligible. Gimatecan 0.8 mg/m2 was administrated orally for five consecutive days every four weeks. Radiological response was assessed every two cycles. Results: From June to December 2005, 70 women [median age 61 years (range 37–79)] were treated in 10 European sites. Number of prior chemotherapy regimens was: 1 in 20, 2 in 35, 3 in 15 patients, respectively. Progression-free interval from last platinum-based therapy was 0–6 months in 51 patients and 6–12 months in 19 patients. The study is still ongoing, and to date 40 consecutive patients are assessable. Preliminary response analysis indicated a 23.5% response rate based on CA 125 (8/34) and a 10% response rate based on RECIST (3/29). Main toxicity was hematological, namely thrombocytopenia and neutropenia. Conclusions: Preliminary results suggest that oral gimatecan administered as single agent is active, with bone marrow suppression resulting at present as the main toxicity in these patients previously treated with platinum and taxanes. However, many patients are still on treatment and data need to mature to have a broader picture of activity and safety. [Table: see text]
Extending the platinum-free interval (PFI) with a non-platinum therapy in platinum (P)- sensitive recurrent ovarian cancer (OC): Results from the SOCRATES retrospective study
Authors: Pignata S. , Odicino F. , Scambia G. , Cormio G. , Katsaros D. , Stellato G. , Scollo P. , Costa B. , Magni G. , Iaffaioli R. V. 
Published: March 2020

5093 Background: Chance of response to P is correlated to PFI (Markman, J Clin Oncol 1991). It has been proposed that extending PFI by interposing non-P therapy increase activity of delayed P retreatment in patients (pts) with P-sensitive recurrent OC, but this strategy is based on data from small series. The SOCRATES study retrospectively assessed the pattern of treatment of a cohort of pts with P-sensitive recurrent OC. Methods: Data of pts treated between 2000 and 2002 at 37 centers were collected in 2005. Pts with recurrent OC were eligible if P-sensitive [interval from end of first line to relapse (RFI) > 6 months]. Results: Data on chemotherapy at relapse were available in 428 pts. RFI was 6–12 months in 40% and >12 months in 60%. Pts received a 2nd (100%), 3rd (80%), 4th (50%), 5th (28%), 6th (12%) line of chemotherapy. 282 pts (65.9%) received P at first relapse (Group A) after a median RFI of 19 months, with a 74.4% response rate (RR) out of 246 evaluable pts. 67 pts (15.7%) received non-P at first relapse after a median RFI of 9.6 months, with a RR of 44.6% out of 56 evaluable pts, and then received P at later relapse after a median PFI of 23 months, with a 57.4% RR out of 47 evaluable pts (Group B). 79 pts (18.5%), with a median RFI of 8.4 months, had a on-P 2nd line with a RR of 28.8% out of 66 evaluable pts, and never received P later (Group C). The difference in RR to P given as 2nd line and delayed P is statistically significant (p = 0.02, Fisher exact test). Median overall survival was 27.2, 26.1 and 16.8 months for Group A, B and C, respectively. Conclusions: With the limits of a retrospective study, our data show that, although P was given in the group B after a similar PFI than in the group A, due to the interposition of a non-P therapy, activity of P was higher when given immediately after relapse than when postponed at subsequent lines. Overall, these data suggest that P-sensitive pts should receive P as soon as possible, and delaying it may preclude the chance of receiving the best treatment. (Study sponsored by GlaxoSmithKline). No significant financial relationships to disclose.
A new measurement of residual cancer burden to predict survival after neoadjuvant chemotherapy
Authors: Symmans W. , Peintinger F. , Hatzis C. , Kuerer H. , Valero V. , Hennessy B. , Green M. , Singletary E. , Hortobagyi G. , Pusztai L. 
Published: March 2020

536 Background: The strength of association between tumor response and survival is critical for neoadjuvant chemotherapy trials. Pathologic complete response (pCR) reliably predicts survival benefit, but residual disease contains a range of pathologic responses that likely contain different prognostic groups, including near complete response and resistance. Methods: Pathologic slides and reports were reviewed from 432 patients in two completed neoadjuvant trials: 1) fluorouracil, doxorubicin and cyclophosphamide (FAC) in 189 patients, and 2) paclitaxel followed by FAC (T/FAC) in 243 patients. Paclitaxel was administered as twelve weekly (n=126) or four 3-weekly cycles (n=117). Residual cancer burden (RCB) was calculated as an index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We compared four RCB categories, from RCB-0 (pCR) to RCB-3 (chemoresistant), and post-treatment revised AJCC Stage (0-III) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses (stratified by ER status). Results: The pCR rate was greater after T/FAC than FAC (24% vs. 16%, LR p<0.05), and after weekly (vs. 3-weekly) paclitaxel in T/FAC (30% vs. 16%, LR p<0.01). In patients with residual disease, RCB measurements were significantly lower after T/FAC than FAC (t-test, p<0.0001), but were not different between paclitaxel schedules in T/FAC. RCB was a continuous predictor of DRFS after T/FAC (HR=1.86, 95%CI 1.51–2.30) or FAC (HR=1.67, CI 1.38–2.01) with median follow-up 5 and 8 years, respectively. The resistant category RCB-3 predicted relapse more strongly than AJCC Stage III and identified a larger group of high-risk patients ( Table ). Conclusions: RCB is a new continuous measure of pathologic response that is defined from routine pathologic materials, represents the distribution of residual disease, is a significant predictor of DRFS, and defines chemotherapy resistance more effectively than revised AJCC Stage. [Table: see text] [Table: see text]
Mortality benefit of switching to an aromatase inhibitor in early breast carcinoma: Pooled analysis of two consecutive trials
Authors: Boccardo F. M. , Guglielmini P. , Rubagotti A. 
Published: March 2020

548 Background: The superiority of new generation aromatase inhibitors (AI) over tamoxifen (T) in the adjuvant treatment of early breast ca. has emerged from several randomized trials. However no mortality benefit has emerged so far from previous trials. Methods: A pooled analysis of GROCTA 4 and ITA trials, two consecutive, multicentric trials performed by our group and sharing the same study design, was performed. The results of both trials have been published previously [JCO 19:4209–15, 2001; JCO 23:5138–47, 2005] and have been updated for the present analysis. In both trials women already on treatment with T for 2 or 3 years have been randomly assigned to continue T for additional 3–2 years or to be switched to aminoglutethimide (AG) or anastrozole (AN) for a comparable time period. In each treatment group mortality was analysed according to cause of death and patient and tumor variables. Results: 828 postmenopausal ER+ve women, most of whom were also node +ve, who had been followed up for a median time of 68 months (range 1–141 months) were analysed. Of these women, 415 had been randomized to continue T and 413 to be switched to AG or AN. In both groups total duration of endocrine therapy was 5 years. All-cause mortality and breast cancer specific mortality were significantly improved by switching: HR=0.60 (0.41–0.87) p=0.007; HR=0.62 (0.39–0.97) p=0.03 respectively. Though more women continued to T died in absence of obvious disease relapse, there was no significant difference between groups in breast cancer unrelated mortality (p=0.1). Multivariate analysis showed that patient age, tumor size, allocated treatment and N status in the order were independent mortality predictors. Tumor size, N status and allocated treatment were independent predictors of breast cancer related mortality as well. Noteworthy, age at randomization was the only statistically significant predictor of breast cancer unrelated mortality. Conclusions: Switching to an AI after 2 or 3 years of T therapy significantly improved survival as compared to 3 or 2 years of additional treatment with T. These findings reinforce the indication to switching for the women actually receiving adjuvant treatment with T. No significant financial relationships to disclose.
Prognostic implication of p53 mutations in HNSCC: Results of Intragroup margin study (E4393)
Authors: Poeta L. M. , Goldwasser M. A. , Forastiere A. , Benoit N. , Califano J. , Ridge J. A. , Goodwin J. , Kenady D. , Sidransky D. , Koch W. M. 
Published: March 2020

5504 Background: The role of p53 as a prognostic marker in head and neck squamous cell carcinoma (HNSCC) is controversial. The intent of this study was to evaluate rigorously the prognostic value of p53 genetic status. Methods: Tumor samples from 480 HNSCC patients treated surgically with curative intent were collected in a prospective multicenter study over 5 years. 57 cases were not analyzed due to technical or administrative factors. Mutation status was determined in the 423 remaining cases, using p53 chip (GP53 GeneChip from Affymetrix, Inc., Santa Clara, CA) which identifies mutations in exons 2 through 11. Indeterminate calls were investigated using Surveyor and/or DHPLC analysis and all mutations were confirmed with an automated fluorescent system or manual sequencing. Clinical follow-up was accomplished following Eastern Cooperative Oncology Group protocol. Results: Median follow-up of the 423 evaluable subjects was 5.4 years with all patients followed at least 3 years. Mutation of p53 gene was present in 224 (53%) cases. There we significantly fewer mutations in tumors arising in the oropharynx (chi-square p = 0.02). The presence of p53 mutation was significantly associated with decreased overall survival. Median survival for patients with tumors with p53 mutation was 3.1 years compared to 5.4 years fro WT tumors (HR = 1.4, 95% CI =1.1 to 1.8, p = 0.01 log-rank test). This proved to be independent of tumor site in multivariate analysis. When mutations were segregated according to their effect on biological function through alteration of key DNA binding domains a Cox regression analysis revealed a statistically significant linear effect of the more disruptive mutations on overall survival with a HR of 1.3 for comparison of each group to the one of lower risk (more vs. less disruptive mutation v. WT (p = 0.001 Wald test). Conclusions: This large prospective series shows a strong relationship between TP53 mutation and prognosis in HNSCC patients. Furthermore, the biological impact of specific mutations has a predictable graded relation to clinical outcome. The results set the stage for use of p53 genetic status in the design of future clinical trials and support the development of targeted therapy to restore wild-type p53 function. No significant financial relationships to disclose.
Analysis of EGFr, VEGF and p53 in serum of head and neck squamous cell cancer (HNSCC) : Preliminary results of the GORTEC 99–02 randomized trial
Authors: Metges J. , Guenet D. , Auperin A. , Gregoire V. , Maingon P. , Lesaunier J. , Calais G. , Zelek L. , Bourhis J. 
Published: March 2020

5509 Background: Predictive and prognostic markers are warranted in HNSCC. We designed a prospective study to analyze EGFr, VEGF and P53 both in the serum and in the tumor of HNSCC patients included in the GORTEC 99–02 prospective phase III trial which compared conventional radiotherapy (RT) plus 5FU and carboplatin (FUP) vs RT with a concomitant boost and FUP vs a very accelerated RT. Methods: This prospective study has been designed to include 820 patients, we present here the results in a sub group of 216 patients for whom the biological markers were analyzed. Association between these markers and TNM staging, age, sex, disease progression and survival was evaluated. Serum analysis was performed for serum EGFr (Oncogene Science), VEGF (R&D systems) and p53 serum-autoantibodies (Immunotech). Statistical analysis were performed using Spearman correlation coefficient, Kruskal-Wallis test for quantitative variables, chi2 and Fischer exact test for qualitative varaibles and Logrank test and cox model for survival analysis. Multivariate analysis of survival took into account T and N status, tumor localisation and the type of treatment. Results: No correlation was found between the serum levels of VEGF and EGFr, neither between EGFr and p53. There was a borderline significant association (p = 0.07) towards higher VEGF serum levels in p53 negative, compared to p53 positive patients. No correlation was found between age, sex, T and N staging and all the serum markers. The VEGF level was significantly higher in laryngeal and hypopharyngeal primaries and lower in oropharyngeal and buccal primaries (p = 0.04). The EGFr level seemed also associated with the tumor localisation (p = 0.055). The median follow up was 2 years. High levels of serum EGFR were associated with better overall survival in univariate and multivariate analysis (p < 0.01). Overall survival was not significantly higher in positive serum p53 patients than in negative p53 patients (p = 0.11 in multivariate analysis). VEGF was not associated with survival. Conclusions: These preliminary resulst suggest that high levels of serum EGFr was associated with a better outcome in this homogenous, prospective series of HNSCC. Work supported by a french PHRC from the National Institutes of Health. No significant financial relationships to disclose.