bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboplatin plus paclitaxel versus carboplatin plus Stealth liposomal doxorubicin in patients with advanced ovarian cancer (AOC): Preliminary activity results of the MITO-2 randomized multicenter trial
Authors: Pignata S. , Scambia G. , Savarese A. , Breda E. , Sorio R. , Vernaglia Lombardi A. , Gebbia V. , Scollo P. , Lorusso D. , Morabito A. 
Published: March 2020

5532 Background: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III study comparing the effect on progression-free survival of carboplatin/paclitaxel versus carboplatin/stealth liposomal doxorubicin (CLD) in 1st-line AOC patients. Due to the lack of published phase II data on the CLD schedule, safety and activity analyses were planned within the trial. The former, previously reported for the first 50 patients treated with CLD, showed mild haematological toxicity, while non-hematological events seldom were higher than grade 2. Methods: AOC patients with AOC (stage IC-IV), aged =75, ECOG PS =2, are randomized to CP (carboplatin AUC 5 / paclitaxel 175 mg/m2, d1q21) or to CLD (carboplatin AUC 5 + Stealth liposomal doxorubicin 30 mg/m2, d1q21), both treatments for 6 cycles. According to a phase 2 design with p0=30%, p1=50%, alfa=0.10, 50 patients with measurable target lesions as defined by RECIST criteria were required and ≥20 responses had to be observed in order to define that the experimental schedule was sufficiently active to warrant phase III continuation. Results: Out of the first 137 patients randomly assigned to CLD, 87 were not eligible for response assessment by RECIST (35 had only non target lesions; 28 had only Ca 125 increased; 23 had no lesion and normal Ca 125; 1 never started treatment). Out the 50 patients eligible for response assessment, overall 34 responses were recorded (14 complete, 20 partial) for a response rate of 68% (95% CI: 53.3–80.5). In addition, among 35 patients with all non-target lesions 9 (26%) complete responses and 18 (51%) nonCR- nonPD were observed. In the remaining 28 patients evaluable only for Ca 125, this normalized in 96% of the cases at the end of the 6 cycles. Conclusions: An a priori planned activity analysis showed that CLD every 3 weeks is feasible and active in AOC patients suboptimally debulked and with measurable lesions. The trial is ongoing; as of December 28th, 2006, 615 patients have been enrolled out of 810 planned. No significant financial relationships to disclose.
The role of surgery in high-risk gestational trophoblastic disease patients
Authors: Lewin S. N. , Soslow R. A. , Kim M. J. , Derosa F. A. , Abu-Rustum N. R. , Sonoda Y. , Brown C. L. , Baines M. S. , Flores R. , Aghajanian C. A. 
Published: March 2020

5541 Background: A survival rate of 81% has been reported in high-risk gestational trophoblastic disease (GTD) patients (pts) treated with multi-agent chemotherapy. We describe the surgical management in heavily treated pts with high-risk GTD. Methods: A retrospective chart review was performed of all pts receiving treatment for GTD at our institution from 1996–2006. High-risk pts who underwent surgery were selected. Results: Over the 10 year period, 32 pts with a median of two prior chemotherapy regimens (range 1–5) underwent 43 surgical procedures. 14 pts (44%) with undesired future fertility had hysterectomies to shorten their chemotherapy interval. 11 remain NED with median follow-up of 24 months (range 8–72). Surgeries to manage disease complications consisted of one craniotomy (for hemorrhage) and one laminectomy (for cord compression). Postoperatively the former received EMA/EP with interval hysterectomy followed by paclitaxel and carboplatin. She remains NED 75 months from diagnosis. The later died one month following laminectomy from pulmonary hemorrhage. Resection of solitary residual disease in chemotherapy refractory pts was attempted for cure in ten pts. Seven pts (70%) were cured following either thoracotomy with wedge resection or lobectomy (6) or radical abdominal trachelectomy (1) with median follow-up of 60 months (range 15 to 84). Of the remaining three, one developed brain metastasis following thoracotomy and was ultimately cured with EMA/EP. The other two with metastatic placental site trophoblastic tumor (PSTT) progressed and died, one and 60 months post-procedure. Planned hysterectomy due to non-metastatic PSTT was performed in two pts as their sole treatment. Both remain NED 19 and 26 months later. An additional seven PSTT pts had hysterectomies following EP/EMA treatment for metastatic disease. Three (43%) of the hysterectomy specimens had no residual disease. All required no further treatment and remain NED with median follow-up of 60 months (range 13 to 84 months). Conclusions: Surgical intervention during the management of high-risk GTD can be tailored to control disease complications, remove chemotherapy resistant disease or serve as therapy for PSTT. A multidisciplinary approach in specialized centers familiar with this disease entity is preferred. No significant financial relationships to disclose.
Concomitant weekly carboplatin (CB) and paclitaxel (P) with pelvic radiotherapy (RT) for the treatment of advanced cervical cancer (ACC): A FNCLCC gynecologic group phase I trial
Authors: Lhomme C. , Petit T. , Largillier R. , Mayer F. , Floquet A. , Rey A. , Jimenez M. , Haie-Meder C. 
Published: March 2020

5542 Background: Standard primary treatment for locally ACC is RT with concomitant chemotherapy (CT). CB and P are radiosensitizers with in vitro synergistic action. Methods: Patients (pts) with FIGO stage IIB-IVA negative paraaortic lymph nodes cervical cancer were treated with 6 weekly cycles of CT during pelvic RT (45 Gy) and brachytherapy (BT) according to Table 1 . Each dose escalation step followed a 30-day period of observation on cohorts of 3 to 6 pts depending on dose limiting toxicity (DLT): toxic death; garde (G) 4 neutropenia > 1 week; G 4 toxicity (other hematologic or non-hematologic); any toxicity requiring = 1 week delay in RT, or > 2 dose reductions of CT, or G 3/4 hematologic toxicity > 3 weeks after treatment’s end; unendurable G 3 non hematologic toxicity. Results: 23 pts were included by 5 centers in 5 dose levels (L). Stage distribution: IIB (10), III (11), IVA (2); 20 epidermoid and 3 adenocarcinoma; ECOG: 0 (16), 1 (7). 22 pts received the 6 planned cycles. Median dose of irradiation was 45 Gy (43.2–50) with no toxicity related interruption. 17 pts underwent BT, 2 had hysterectomy and 1 received complementary external irradiation 12 Gy. CT dose reduction was necessary in 4 pts (cycle 5 or 6) and cycles postponed for 10 pts (cycle. 5 or 6). One pt experienced paclitaxel allergy at L1. G 3 anemia and/or neutropenia were reported in 11 pts and G 4 neutropenia = 1 week in 2 pts. Radiodermatitis occurred in 5 pts, asthenia in 3 and nausea in 1. One DLT was observed: unendurable G 3 asthenia + G 3 neutropenia and leucopenia at L3. Clinical and radiological complete response was obtained in 13 pts, 5 PRs and 2 SDs in 20 evaluable pts. Conclusions: Acceptable toxicity and optimal irradiation were possible at L4 in 7 pts. These doses are recommended for future phase II studies of concomitant CT/RT in ACC. [Table: see text] No significant financial relationships to disclose.
Cervical cancer in patients infected with human immunodeficiency virus (HIV)
Authors: Leitao M. M. , White P. , Cracchiolo B. M. 
Published: March 2020

5544 Background: The objective of this study was to compare the HIV viral load (VL), and CD4 counts (CD4) in patients infected with HIV with and without cervical cancer. We hypothesize that HIV positive women with inadequate HIV control, as reflected by the degree of immune suppression, will be at the highest risk of developing cervical cancer. Methods: We performed a case-control study of all patients seen at University Hospital from 1/1/95 - 4/30/06. All patients were HIV positive and were identified using an institutional electronic patient database and University Hospital Cancer Registry using ICD-9 codes. Cases were patients diagnosed with invasive cervical cancer and controls were patients without invasive cervical cancer. Patients were used as a control if there was documentation of a normal gynecologic exam without clinical or histopathologic evidence of cervical cancer. CD4 counts and viral loads were then abstracted from the electronic medical chart. Patients were kept as cases or controls if they had a CD4 count <6 months before or <1 month after the diagnosis of invasive cervical cancer (cases) or from the last gynecologic exam (controls). Controls were matched to cases on a 4:1 ratio according to current smoking history. Patients were considered immunocompetent if they had both CD4 counts >200 and VL <10,000. SPSS version 12.0 statistical software was used to analyze our data. Results: A total of 15 cases and 60 controls were identified. The majority (67 [89%]) of patients were African-American. The median CD4 count for the cases was 208 (range 18 - 1102) compared to 445 (range 20 - 1201) for the controls (p=0.03). The median VL was 16,918 (range 50 - 214,915) for the cases compared to 1,430 (range 50 - 571,000) for the controls (p=0.15). Only one (7.1%) of 14 cases was immunocompetent compared to 35 (63.6%) of 55 controls (OR 0.04 [95% CI: 0, 0.37; p<0.001]). This significance was maintained after adjusting for current highly active antiretroviral therapy (HAART) use, number of years known to be HIV infected, and patient age (p=0.002). Conclusions: Patients with HIV who are diagnosed with invasive cervical cancer appear to have a much greater degree of immunosuppression than women with HIV without invasive cervical cancer. No significant financial relationships to disclose.
SCOTCERV: A phase II trial of docetaxel and gemcitabine as second-line chemotherapy in cervical cancer
Authors: Symonds R. , Davidson S. , Chan S. , Reed N. , McMahon T. , Paul J. 
Published: March 2020

5548 Background: Concurrent Cisplatin chemotherapy along with radiotherapy is standard therapy for locally advanced cervical cancer. There is no established second line regimen. Taxanes and Gemcitabine are not thought to share drug resistance with Cisplatin. In combination they are reasonably tolerated; myelosuppression is the dose limiting toxicity. Response is more likely in recurrences outside the irradiated area. Methods: This was a multi-centre phase II trial of Docetaxel (75mg/m2 d1) and Gemcitabine (1,000 mg/m2 d1,d8) in relapsed patients (pts) after treatment with cisplatin alone or in combination (excluding with taxanes) and/or radiotherapy. A Gehan two-stage design was used (minimum response rate requirement 25%). Pts had to have disease assessable by RECIST outside the irradiated pelvis and adequate organ function. After 12 pts the Docetaxel dose was reduced to 60 mg/m2. Results: 26 eligible pts were recruited to the study; information is available currently for 24. The median age is 43 years (range 30–62) and the median time from prior treatment is 12 months (1–55). 23 pts had prior chemoradiotherapy. Performance status: 0 (15) or 1 (9). Histology: squamous 17, adenoCa (6) mixed (1). Major metastatic sites were lung (11) and para-aortic nodes (11). The principal toxicity was neutropenia (gd 3 (8), gd 4 (8)) with 4 pts experiencing grade 3 febrile neutropenia. Dose reductions occurred in 29% of pts (Docetaxel) and 25% of pts (Gemcitabine), primarily for neutropenic fever. Haematological toxicity resulted in d8 Gemcitabine being omitted in 41% of cycles. 1 patient had gd3 SOB and 1 patient gd 3 diarrhoea. Reduction of Docetaxel dose did not reduce haematological toxicity. 5 pts have not, as yet, had response reported. In 19 pts (16 completed therapy) there was 1 CR, 4 PR, 6 stable disease, 7 progressions and 1 unevaluable. The overall response rate is 26% (95% ci 9%-51%). Conclusions: This preliminary data shows this combination has activity against platinum resistant metastatic cervical cancer, although the ability to deliver d8 Gemcitabine is compromised. Final results will be available for the meeting. [Table: see text]
Oxaliplatin plus paclitaxel for recurrent and metastatic cervical cancer (CC): New York Cancer Consortium Trial P5840
Authors: Kuo D. Y. , Blank S. V. , Kobrinsky B. , Christos P. , Caputo T. A. , Runowicz C. D. , Pothuri B. , Ivy P. , Muggia F. , Wadler S. 
Published: March 2020

5549 Background: Although cisplatin (cis) is an effective radiosensitizer, its activity in patients (pts) with advanced and recurrent CC is disappointing. Oxaliplatin (O) might exhibit greater activity and be suitable for combination with paclitaxel (P). Methods: Pts with advanced and recurrent CC who had not received prior chemotherapy except radiosensitizing cis were treated with P 175 mg/m2 IV and O 130 mg/m2 IV every 21 d. Response (R), as determined by RECIST criteria and confirmed at 9 weeks (wk), and toxicity were primary outcomes. If R in = 8 patients (pts) of 18, accrual to 46 could ensue. Results: Of 17 pts enrolled, 16 were treated. Histology: 7 adeno/10 squamous.The median age was 57 (range 33–78) and 13 had had prior radiation (10 with cis). Median cycles: 3 (0–8). One CR and 4 PRs were achieved for an overall response rate of 29% (95% confidence interval: 10.3%, 56.0%). Additionally, 4 had stable disease, but this was not confirmed at 15wk. Time to progression in those responding was 21 wk (range 11–51). 7 pts are alive. 6 pts experienced grade (gr) 3/4 hematologic toxicity. Neuropathy occurred following cycle 3 in 2 pts (gr3). Additonal gr 3/4 toxicities were gastrointestinal (GI)/metabolic in 6, thrombotic in 1 and hypersensitivity in 1. There were no treatment-related deaths. Conclusions: In the stage I of our Phase II trial, O and P demonstrate a 29% response rate when used to treat advanced and recurrent CC. Toxicities of this regimen are hematologic, gastrointestinal, and neurologic. Supported by N01-CM-62204. No significant financial relationships to disclose.
A stromal-associated gene expression signature predicting for survival in a series of patients with advanced high-grade serous ovarian cancer
Authors: Bonome T. , Samimi G. , Randonovich M. , Brady J. , Ghosh S. , Ng S. , Mok S. C. , Birrer M. J. 
Published: March 2020

5552 Background: Prognostic gene expression signatures have been derived for undissected serous ovarian epithelial tumors, yet the specific contribution of stromal cells to patient survival has not been addressed. The aim of this study is to identify stromal genes impacting patient survival in the context of serous ovarian cancer. Methods: Expression profiling utilizing Affymetrix U133 Plus 2.0 oligonucleotide arrays was completed for 50 microdissected stromal samples derived from high-grade, late-stage serous tumors displaying a broad spectrum of survival endpoints. A semi-supervised dimension reduction method employing multivariate Cox regression and principal components analysis was applied to the expression data to identify genes associated with patient survival and establish a predictive model. qRT-PCR was employed to validate the microarray expression data. Results: Cox regression analysis identified 267 significant genes. The first 6 principal components of these genes, representing >65% of total variance, entered a multivariate Cox model through which the relative hazard of future patients can be predicted. To confirm our finding, the microarray data underwent leave-one-out validation. The patients were equally divided into low- and high-risk groups and non-parametric Kaplan-Meier analysis and log rank test demonstrated the two groups were significantly different in survival (p = 0.0115). Genes associated with cell survival and migration were identified in the prognostic signature. For validation, qRT-PCR data for all 50 specimens was correlated with microarray expression values for a series of select prognostic genes. Conculsions: In this study, we characterized and validated a stromal dervied prognostic signature associated with poor patient survival. Contained in this novel predictor may be stromal targets suitable for the design of new therapeutic interventions, or use as independent diagnostic markers. No significant financial relationships to disclose.
A phase I study of MORAb-003, a fully humanized monoclonal antibody against folate receptor alpha, in advanced epithelial ovarian cancer
Authors: Bell-McGuinn K. M. , Konner J. , Pandit-Taskar N. , Gerst S. , Nicolaides N. , Sass P. , Grasso L. , Weil S. , Phillips M. , Aghajanian C. 
Published: March 2020

5553 Background: Folate receptor alpha (FRA) is over-expressed in the majority of epithelial ovarian cancers (EOC) but is largely absent from normal tissue. MORAb-003 is a humanized monoclonal antibody (MAb) to FRA. Binding of MORAb-003 to FRA can prevent phosphorylation of substrates specific for Lyn kinase, suppress proliferation of cells over-expressing FRA, mediate FRA-positive tumor cell killing via antibody-dependent cellular and complement-dependent mechanisms, and suppress tumor growth in vivo of FRA-expressing tumors in rodent xenograft models. Toxicology studies in non-human primates found no evidence of toxicity with MORAb-003 at supra- pharmacological doses. This open-label, multiple-infusion, first-in-human, dose-escalation trial evaluates the safety, pharmacokinetics (PK), and anti-tumor activity of MORAb-003 in patients with platinum-resistant EOC. Methods: Sequential cohorts of patients received four weekly infusions at escalating dose levels of MORAb-003 from 12.5 mg/m2 to 400 mg/m2. Eligible patients had platinum-resistant EOC, acceptable organ function, KPS = 70%, and measurable disease by GOG-RECIST criteria. A subset of subjects received a tracer dose of 111In-labelled MORAb-003 and SPECT-CT and planar imaging. Human anti-human antibody (HAHA) and PK analyses were performed. Results: To date, 18 subjects have been dosed with up to 200 mg/m2. No dose limiting toxicity or significant related adverse events have been observed. Four subjects had rigors (2 grade 1) or fevers (3 grade 1, 1 grade 2) following the first infusion. Nine subjects have had radiologically stable disease, and 7 subjects have had stable or declining CA125. Two subjects have received extended therapy for an apparent clinical benefit. Radiolabelled tracer studies have demonstrated significant tumor uptake of labeled MORAb-003. The 400 mg/m2 dose cohort is currently enrolling. Conclusions: The FRA-specific MAb MORAb-003 appears to be well tolerated in patients with EOC and may have activity in platinum-resistant patients. These results support further evaluation of the efficacy of MORAb-003 in a phase 2 study which is ongoing. [Table: see text]
High plasma levels of fenretinide (4-HPR) were associated with improved outcome in a phase II study of recurrent ovarian cancer: A study by the California Cancer Consortium
Authors: Reynolds C. P. , Frgala T. , Tsao-Wei D. D. , Groshen S. , Morgan R. , McNamara M. , Scudder S. , Zwiebel J. A. , Lenz H. J. , Garcia A. A. 
Published: March 2020

5555 Background: 4-HPR is a synthetic retinoid with dose-dependent cytotoxicity in vitro for ovarian cancer cell lines, especially at concentrations > 10 μM. We previously reported preliminary results of a phase II trial (Garcia et al, Proc ASCO 2004: a5056) that showed encouraging stabilization of disease. Methods: 4-HPR capsules were given orally (900 mg/m2/bid for 7 days every 21-days) to women with recurrent ovarian cancer. Steady-state plasma concentrations of 4-HPR were determined by HPLC. Patients were required to have uni-dimensionally measurable disease, 0–2 chemotherapy regimens for recurrent disease, and performance status 0–2. The primary endpoint was response rate by RECIST criteria; secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: 31 patients were enrolled to the first stage; 28 patients were evaluable for response, with a median of 3 prior chemotherapy regimens (range: 1–3); 24 patients were evaluable for pharmacokinetics. A total of 172 4-HPR treatment cycles were given. Eleven patients experienced at least one grade 3 toxicity and one patient had grade 4 fatigue. No objective responses were observed, leading to study closure. Best response was stable disease in 13 patients (42%) with a median duration of 7.9 months (2.1–25.8 months). 4-HPR steady-state plasma levels ranged from 3.1–12.5 μM. PFS at 6 months was 26% (± 0.08 SE), 42 % (± 0.14 SE) for patients with 4-HPR plasma levels = 9 μM (n=12), and 17% (± 0.11 SE) for plasma levels < 9 μM (n=12). OS with plasma levels = 9 μM was significantly higher than for those with 4-HPR levels < 9 μM (66% vs. 13% at 18 months, adjusted p-value = 0.016). Conclusions: 4-HPR may provide clinical benefit to patients with recurrent ovarian cancer who obtain high 4-HPR plasma levels. Trials in ovarian cancer of 4-HPR focused on progression-free survival as an endpoint are justified using formulations with improved bioavailability. Supported by N01-CM-62209. No significant financial relationships to disclose.
Randomized, multicenter, two-dose level, open-label, phase IIa study with the intraperitoneally infused trifunctional bispecific antibody catumaxomab (anti-EpCAM × anti-CD3) to select the better dose level in platinum refractory epithelial ovarian cancer patients
Authors: Belau A. , Pfisterer J. , Wimberger P. , Kurzeder C. , Du Bois A. , Sehouli J. , Loibl S. , Burchardi N. , Vergote I. , Wagner U. 
Published: March 2020

5556 Background: The trifunctional antibody catumaxomab specifically binds EpCAM+ tumor cells, CD3+ T lymphocytes and accessory cells via the Fcγ RI/III thereby inducing a tumor specific cell mediated cytotoxicity in vitro and in vivo. This study was conducted to evaluate efficacy and safety of two different regimens of catumaxomab. Methods: Women with platinum-refractory (progressing during or ≤ 6 mos. after the last platinum containing regimen) epithelial ovarian cancer and measurable recurrent disease were randomized to receive either 10 -10 -10 - 10 μg or 10–20–50–100 μg of catumaxomab over 6h i.p on days 0, 3, 7 and 10. Results: 45 pts. were entered (22 high dose (HD)-arm, 23 low dose (LD)-arm). Both groups were well balanced concerning ECOG-perfomance score, with a median age of 65.6y in the HD- and 57.6y in the LD-arm and with a median diameter of measurable lesions of 90mm in the HD- and 104mm in the LD-arm. Based on the AEs, changes in laboratory parameters and other safety variables observed in the safety population in the course of this study, the accumulated safety experience is consistent with the key features of the mode of action of catumaxomab. Their intensity on median level was mostly mild to moderate. A clinical benefit was detectable in 27.3% of pts. for the HD- (1PR/5SD) and 8.7% of pts. for the LD-arm (2SD). After a median follow-up of 4.96 months, the median overall survival time was 182 d for the HD- and 114 d for the LD-arm. Conclusion: The results demonstrate that catumaxomab is safe with acceptable toxicity when administered as a sequence of 4 IP infusions at 10, 20, 50 and 100 μg. A modest dose effect is observed for the higher doses of catumaxomab. No significant financial relationships to disclose.