tbuckley/cabot-search huggingface dataset:
Prognostic significance of minimal pleural effusion in non-small cell lung cancer patients.
Authors: Jeong Seon Ryu, Si-Nae Lee, Hyo-Jin Ryu, Hae-Seong Nam, Azra Memon, Hyun-Jung Kim, Joo Han Lim
Journal: Journal of Clinical Oncology (2013)

e19152 Background: Malignant pleural effusion (MPE) was defined by the presence of malignant cells in pleural space. Accurate characterization of pleural effusion (PE) is an essential part in staging the disease for adequate management. At diagnostic evaluation, minimal pleural effusion (mPE) that is too small amount PE to examine the presence of malignant cells through thoracentesis is present outside scope of current staging system. Therefore whether mPE has prognostic impact or not is an important clinical issue needed to be investigated. Methods: 1,382 consecutive stage IIIB, IV NSCLC patients were retrospectively enrolled from Inha Lung Cancer Cohort. Information regarding smoking habits, ECOG PS, Charlson comorbidity index score, weight loss in 6 months before diagnosis, levels of hemoglobin, albumin, alkaline phosphatase and calcium at the time of diagnosis, treatment, followed-up and survival status was analyzed as potential confounding factors. All patients were performed staging work-up and followed-up at Inha university hospital. The mPE was defined as less than 1 cm of maximal thickness on contrast enhanced chest CT scan at diagnosis and its presence was not considered in staging the disease. Results: According to status of PE at diagnosis, patients were classified into no PE, mPE and MPE. No PE was presented in 614 patients (44.4%); mPE in 339 patients (24.5%); malignant PE in 356 patients (25.8%). PEs of 73 (5.3%) patients was not evaluated. Overall survival of patients with mPE or MPE was shown to be significantly shorter than those of patients with no PE (MST, 9.67 for no PE, v 6.60 for mPE v 5.37 months for MPE, log-rank p&lt;.0001), even after adjustment for age, smoking habits, ECOG PS, Charlson comorbidity index score, weight loss, hemoglobin, albumin, alkaline phosphatase, calcium, histology, T subset, N subset, M subset, and treatment status (hazard ratios, 95% CIs and Cox p: 1.18, 1.023 to 1.373 and .024 for mPE; 1.545, 1.314 to 1.816 and &lt;.0001 for MPE). Conclusions: The mPE is commonly encountered clinical situation in advanced stage NSCLC patients. These results suggest that presence of mPE at diagnosis confers grave prognosis like MPE, in spite of its nature.
A Phase I and pharmacokinetic study of HMN-214, a novel oral polo-like kinase inhibitor, in patients with advanced solid tumors
Authors: D. D. Von Hoff, C. Taylor, S. Rubin, J. Cohen, L. Garland
Journal: Journal of Clinical Oncology (2004)

3034 Background: HMN-176 is a stilbazole derivative with potent antitumor activity in preclinical models. HMN-176 interferes with localization of polo-like kinase 1(PLK-1). PLK-1 is upregulated in multiple malignancies including pancreatic cancer (Gray, et al. Proc. AACR, Vol 44, 2nd ed: 919, 2003). HMN-214 is a prodrug of HMN-176 with improved oral absorption. We performed a dose escalation trial of HMN-214 to establish its toxicity and pharmacokinetic (PK) profiles and maximum tolerated dose (MTD) when administered daily × 21 days every 28 days. Methods: Patients (pts) had advanced solid tumors, adequate organ function and performance status 0–2. HMN-214 was escalated in cohorts of 3, with expansion if 1/3 pts on a dose level had a dose-limiting toxicity. Results: 33 pts (median age 66; M:F 19:14) have received 71 cycles HMN-214. Pts were treated at 3, 6 and 9.9 mg/m2/d. At 9.9 mg/m2/d, 1 pt had grade 3 hyperglycemia, chest pain (non-cardiac) and myalgias and 1 pt had grade 3 bone pain. Pts were then stratified into Lightly Pretreated (LPT) and Heavily Pretreated (HPT) cohorts and treated at de-escalated levels of 3, 6 and 8 mg/m2/d. One of 6 LPT pts at 8 mg/m2/d had grade 3 bone pain; no HPT pts at 8 mg/m2/d had DLT. One pt had grade 3 anemia; no other gr 3 and no gr 4 hematologic toxicity was seen. PK studies on day 1 of dosing indicate the active compound (HMN-176) reaches maximum concentration 2.2 to 6.7 hours after oral dosing and t1/2varies from 11.8 to 15.8 hours. Cmax and AUC0–24 increased appropriately according to dose. Antitumor activity was noted in a colon cancer pt at 9.9 mg/m2/d with a transient decrease (40%) in CEA after cycle 1, a breast cancer pt at 9.9 mg/m2/d with stable disease for 6 months, and bronchial carcinoid pt at 8 mg/m2/d with stable disease at 2+ months. Conclusions: HMN-214 is a novel oral PLK-1 inhibitor with an excellent toxicity profile and dose-linear PKs when administered on a daily × 21 schedule. The MTD and the dose recommended for Phase II trials is 8 mg/m2/d, with no difference in tolerance in LPT and HPT pts. Given the early indications of antitumor activity, HMN-214 will be investigated as a novel therapy in Phase 2 trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NS Pharma
The role of MGMT promotor hypermethylation as a predictive factor for response to temozolomide in recurrent high-grade glioma
Authors: J. Sadones, A. Michotte, C. Chaskis, P. In ’t Veld, S. Califice, K. Bierau, C. Svensson, J. De Grève, B. Neyns
Journal: Journal of Clinical Oncology (2007)

12509 Background: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promotor hypermethylation (MGMT-meth) compromises DNA repair of high-grade glioma (HGG) and has been associated with a survival benefit in patients treated with temozolomide (TMZ) for newly diagnosed glioblastoma multiforme (GBM). It remains undetermined if the MGMT-meth status correlates with response to temozolomide at recurrence and whether extended dosing of TMZ (known to deplete MGMT in peripheral blood mononuclear cells) can overcome resistance in unmethylated HGG. Methods: We are investigating the MGMT-meth status on glioma tissue samples collected at diagnosis from 64 patients (pts). Fifty pts were treated at the time of recurrence with conventional TMZ (5 out of 28d regimen) and 14 pts with extended dosing of TMZ (100 mg/m 2 /d, 21 out of 28d regimen). Following DNA isolation from archival glioma tissues by phenol/chloroform extraction and a bisulphite conversion of genomic DNA, real-time methylation-specific PCR quantification of the methylation status of the MGMT promotor region is performed by OncoMethylome Sciences S.A. (according to OMS proprietary methodology). Results: At present, results have been obtained for 15 pts (13 M/ 2 W, median age: 46y). From 3 pts a biopsy at recurrence was available for analysis. The result was discordant with the MGMT-meth status at diagnosis in 2 pts (1x meth to unmeth and 1x unmeth to meth). Of the 6 (40%) pts with MGMT-meth gliomas, none had immediate progression on TMZ (respectively 4x SD, 1x CR, 1x PR). Of the 9 pts with an unmethylated MGMT promotor, 4 pts had immediate progression on TMZ and 5 pts had SD (of which 4 had been treated with the 21/28d regimen). All pts, except one, with MGMT-meth had a TTP that was above the median of our study population. The two pts with an MGMT-unmeth status that had a TTP above the median had received the extended dosing regimen. Conclusions: Our preliminary data indicate that MGMT promotor hypermethylation at diagnosis might correlate with sensitivity to TMZ in the recurrent setting. Extended dosing of TMZ might be more active against MGMT-unmethylated glioma. Final data from this study will be available for presentation at the meeting. No significant financial relationships to disclose.
Induction chemotherapy with docetaxel, cisplatin, 5 FU, followed by radiotherapy plus cisplatin or cetuximab, in organ preservation in piriform sinus carcinomas.
Authors: Jerome Fayette, Carine Fuchsmann, Sophie Tartas, Veronique Favrel, Pascal Pommier, Philippe Zrounba, Antoine Ramade, Severine Racadot, Philippe Ceruse, Marc Poupart
Journal: Journal of Clinical Oncology (2013)

e17011 Background: Only few studies report organ preservation in piriform sinus carcinomas (PSC), with no publication on induction chemotherapy (IC) with docetaxel, cisplatine, 5FU (DCF) followed by radiotherapy plus cisplatin (RTCis) or cetuximab (RTCet). We assessed compliance, survival and organ preservation after IC by DCF followed by RTCis or RTCet in a retrospective multicentric review of patients (pts) with advanced PSC. Methods: We analyzed retrospectively 88 pts with advanced PSC treated between 2005 and 2011 in 3 tertiary care centers with organ preservation protocol strategy ongoing in each center. DCF was followed by RTCet (56.5%) in 1 center and by RTCis(42%) in the 2 others. Primary endpoints were acute toxicity and compliance to IC and RTCis compliance compared with RTCet. Secondary endpoints were overall survival (OS), disease free survival (DFS) and laryngectomy free survival (LFS). Results: Within the 88 pts, 21.6% were stage III and 72.7% stage IV; 81% completed the full course of IC. For 64.8% of pts no toxicity was reported. The main side effect observed was neutropenia (18.2%). Two deaths (2%) were directly related to the IC. Concerning the radiotherapy, 59% of the pts had full dose concomitant cisplatin versus 85% with cetuximab (p&lt;0.001). Mean follow up was 23.5 months. At 5 years, OS rate was 35.5%, [CI 95% 24.6%-50.7%]. At 4 years DFS rate was 24% [CI 95% 15.5%-38%]. Factors affecting survival were IC response (ICR) (p&lt;0.001) and stage of the disease (stage II&gt;stage IV, p&lt;0.001). No significant difference in survival was found between patients with RTCis or RTCet. At 4 years, LFS rate was 73% [IC 95% 56%-87.6%]. Factor affecting this LFS rate was ICR (p&lt;0.05). Conclusions: IC with DPF followed by RTCis or RTCet allowed high organ preservation rates with acceptable toxicities. Cetuximab seemed to be better tolerated than cisplatin, improving compliance to the treatment. OS favorably compared with historical data of concurrent chemoradiation
A phase II study of biweekly paclitaxel and cisplatin chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma: Role of ERCC1 expression.
Authors: Jing Huang, Yi Zhou, Tao Qu, Hong-Tu Zhang, You-Sheng Mao, Hong-Xia Zhu, Lan-Ping Quan, Pu-Yuan Xing, Jin-Wan Wang, He Jie, Ning-Zhi Xu
Journal: Journal of Clinical Oncology (2012)

e14502 Background: Recurrent or metastatic esophageal cancer has poor prognosis. Currently, the standard of care for esophageal cancer includes treatment with triweekly cisplatin-based chemotherapy. However, not all patients benefit from the treatment. To improve the response and identify specific marker for patient-personalized treatment, we designed this study to assess the efficacy and safety of biweekly paclitaxel and cisplatin combination for patients with recurrent or metastatic esophageal squamous cell carcinoma. The excision repair cross-complementation group 1 (ERCC1) expression to predict response is also assessed. Methods: Forty-six eligible patients were enrolled. Paclitaxel was given at 150 mg/m 2 over 3 hours on day 1 and cisplatin was given at 50 mg/m 2 on day 2, every 2 weeks as one cycle. ERCC1 protein expression was assessed by immunohistochemistry staining. Results: The overall response rate was 56.5% (26/46, 95% CI 42.2 %- 70.8%). Progression-free survival was 5.6 months (95% CI, 2.8-8.4 months) and the median actuarial survival time was 17.0 months (95% CI, 12.3-21.7months). There was a significant difference in median actuarial survival between the patients with a response compared to the non-responders (22.8 months vs. 7.4 months, p&lt;0.0001). Overall survival at 1 year was 65.0%, and at 2 years was 34.0%, respectively. The most frequent toxicity for all patients was neutropenia (37.0% and 23.9% for grades 3 and 4, respectively). Patients with ERCC1 negative tumors had a higher treatment response than the ERCC1 positive group (radiological response rates; 92.3% vs.50%, p=0.013). Conclusions: Biweekly chemotherapy with paclitaxel and cisplatin was found to be active and generally well-tolerated. Our study indicates that expression of ERCC1 evaluated by immunohistochemistry is a promising predictive marker for response in patients with metastatic ESCC receiving cisplatin-paclitaxel regimen.
Safety of trabectedin (T) in elderly patients (pts) with advanced soft tissue sarcoma (STS).
Authors: Roberta Sanfilippo, Giacomo Giulio Baldi, Elena Fumagalli, Andrea Marrari, Rossella Bertulli, Elena Palassini, Silvia Stacchiotti, Michela Libertini, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2013)

10576 Background: T is a marine-derived cytoxic alkaloid approved in the European Union for further-line chemotherapy of advanced STS. Most common side effects are fatigue, neutropenia and transient transaminitis. Overall the drug is well tolerated with no cumulative toxicity. Studies in elderly pts are lacking. Methods: We retrospectively reviewed all pts ≥65 year-old, with pre-treated advanced STS, who received T at our Institution from January 2002 to January 2013, focusing on tolerability. All patients received premedication with dexamethasone 4 mg p.o. bid 24 hours prior to T administration. Treatment toxicity was graded according to CTCAE (v 4.0). Results: Fourty-two pts were identified (males = 22, females = 20; median age = 69 years, range 65-82; ECOG PS 0 = 1 pt, 1= 38 pts and 2-3= 3 pts; main histotypes = 22 liposarcoma: 12 myxoid-round cell liposarcoma, 10 well/dedifferentiated liposarcoma, 17 leiomyosarcoma, 2 synovial sarcoma, 4 others; disease extent = 34 metastatic and 8 locally advanced; median line of administration of T= 3 rd , range 1 st -5 th ; median T dose = 2.2 mg, range = 2.7-1.7 mg). A total of 319 cycles were administered (median 6, range = 1-23). Starting dose was 1.3 mg/mq in 37 pts and 1.1 mg in 5 pts. The most common side effects were: fatigue (all grades: 19% of cycles), reversible myelosuppression, mainly neutropenia (grade 3-4: 50%), transient transaminitis (grade 3-4: 21%). Eighteen pts needed a dose reduction: inter-cycle transient transaminitis (3 pts), neutropenia ( 13 pts), asthenia (2 pts). In 7 patients, cycles needed to be delayed as well. Three pts interrupted T due to toxicity: grade 3 thrombocytopenia in 1 pt and grade 4 neutropenia in 2 pts. Conclusions: This retrospective analysis confirms that T is well tolerated in elderly pts. No major differences were found in the safety profile compared to historical controls, except a higher incidence of myelosuppression, which however was not influential on subsequent T administration.
Postoperative radiotherapy (RT) with or without chemotherapy (CT) in anaplastic astrocitoma (AA) patients.
Authors: Sonia Brugnara, Lucianna Russo, MariaChiara DiPasquale, Michele Nagliati, Gianpaolo Basso, Diego Trevisan, Franco Chioffi, Giuseppe Pulcrano, Enzo Colarusso, Mattia Barbareschi, Umberto Rozzanigo, Andrea Pellegrin, Dante Amelio, Davide Donner, Manuela Buganza, Elena Magri, Monica Dallabona, Nicola L Decarli, Enzo Galligioni
Journal: Journal of Clinical Oncology (2013)

e13046 Background: Although the evidence for the benefit of adding temozolamide (TMZ) to RT is limited to glioblastoma patients (pts), there is currently an increased tendency toward a combined RT + TMZ approach also in AA patients. Methods: We report in this study the survival outcome of 2 groups of pts, treated at in 2 different periods at our institution with RT after surgery ± CT. GROUP A (years 1984-2001): pts treated with surgery followed by RT; GROUP B (YEARS 2004-2009): pts treated with surgery followed by radical RT and CT according to the STUPP’s protocol; Results: Data were retrospectively collected on a consecutive series: GROUP A: 17 pts: 10 Males (M), 7 Females (F); median age 50 years (range: 31-65). Ten out of 17 pts received radical surgery and 7 subtotal surgery. All were treated with postoperative RT, median dose 5082 cGy (range: 2160-6300). The mean time between surgery and beginning of RT was 44.7 days (range 20-87). GROUP B: 17 pts: 10 M, 7 F; median age 44 years (25-72). Eleven out 17 pts received radical surgery and 6 subtotal surgery. All were treated with postoperative RT, median dose 5800 cGy (range: 4000-600). The mean time between surgery and beginning of RT was 56.3 days (range 26-111). All patients received TMZ 75 mg/mq for a median of 6 weeks (range 3-7), followed by adjuvant treatment with TMZ (200 mg/mq) for a median of 5 cycles (range 0-13). At a median follow-up of 45 mos , the median OS was 29.1 mos for the group A and 49,1 mos for the group B. Among pts treated with RT + CT after surgery, median OS was significantly longer (p= 0.03), compared to those treated with only RT after surgery. Conclusions: The limited sample sizes of 2 groups and differences such as the median RT dose and the median time between surgery and RT, does not allow any conclusion. However, our data suggest that the combined RT-CT treatment is feasible in AA pts after surgery and may possibly contribute to a prolonged control of disease. These suggestions should be explored in a prospective randomized trial.
Cumulative impact of algorithm-integrated multidisciplinary treatments for cholangiocarcinoma.
Authors: Azriel Hirschfeld, Howard Bruckner, Jeanetta Stega, Myron E. Schwartz
Journal: Journal of Clinical Oncology (2012)

e14732 Background: Pancreatic Ca (PC) treatments (rxs) are often applied to patients (pts) with cholangioC (CC). Analyses support parallel "testing" of neoadjuvant (NeoA) and adjuvant (A) rx for CC pts. The rxs below “doubled” phase II objective response (OR) and survival (OS) vs PC. Methods: With pre-registration and IRB consent over ten years: GFLIP&gt;GFLIO &gt;GFLIO docetaxel (D) -/+mitomycin -C (MM-C) (Bruckner ASCO 01, 05, 08, 11) were applied to pts with PC and CC; stage adjusted, “possible best" choices for PC rxs were applied as NeoA and A rxs for high risk CC pts. Risk was defined by: margin, +; size, large; location, surgical difficulty, central; LNs, involved (or suspect), number of sites (and distance); pathology, atypical, high virulence and relapse (second surgery). These are the worst half of resected pts. Pts with unresectable (U) and metastatic (IV) CC were eligible with or without prior failure of some of the rx drugs. Targeted rx (TT) was briefly added, bevacizumab (B) 5mg/kg or cetuximab (C), as needed, to convert stable disease (SD) to NeoA eligible OR. Gallbladder Ca (GBC) pts were also treated. The algorithm's goal was to both optimize surgery for tumor reduction to improve rx and to select “timely” drug partners to reduce tumor size and allow further surgery. Results: No fatal AEs; Of 16 high risk, Adjuvant, resected pts, at 18 mos, 14 are alive, 10/11at 2 yrs, 6/7 (86%) at 3 yrs, 1 lost contact CC U/ IV, N=28, 4 lost contact 16/19 (84%) alive at 18 mos; 12/16 alive at 2yrs; 8/12 alive at 3 yrs. This vs. 50% (18mo) MST (ASCO 11). Of 7 NeoA, 4/4 were alive at 3 yrs, 3 others alive &lt; 3 yrs. (3 had best R with TT). *RR GFLIO ~ 60% add DMM-C ~ 60% € ~84% add TT ~20% €~ 87%. Conclusions: Rxs are safe, economical and well tolerated. € RR and OS adding (FI, D, D-MMC and selectively TT) are testworthy. Both 12 mos OS and NeoA/A are testworthy for GBC pts. B and C are individually active, safe and cost effective in brief NeoA usage applications. Low dose multi drug rxs are ideal safe platforms for TT. High serial € RR encourage 1° and 2° attempts at both debulking - strategic palliative and definitive surgery, ideally in trials to optimize (pt conditioning, eligibility) and compare NeoA vs A rxs.
Effectiveness of bevacizumab added to gold standard chemotherapy in metastatic colorectal cancer (mCRC): Final results from the Itaca randomized clinical trial.
Authors: Alessandro Passardi, Emanuela Scarpi, Luigi Cavanna, Annalisa Fontana, Bernadette Vertogen, Silvia Ruscelli, Emiliano Tamburini, Angela Ragazzini, Giovanni Luca Frassineti, Oriana Nanni, Dino Amadori
Journal: Journal of Clinical Oncology (2013)

3517 Background: Evidence from available RCTs indicates that the addition of bevacizumab (B) to chemotherapy (CT) results into an improved survival in metastatic colorectal cancer (mCRC). However, the magnitude of this effect is different across trials, with marginal benefit observed when gold standard CT regimens are used. With these premises we performed a phase III randomized clinical study to evaluate the effectiveness of gold standard mCRC first line CT + B. This study was funded by the Italian Ministry of Health. Methods: mCRC patients candidate were randomized to receive first line CT +B or first line CT alone. CT regimens included FOLFOX4 (oxaliplatin 85 mg/m 2 d1, folinic acid FA 100 mg/m 2 dd1,2, 5FU 400 mg/m 2 iv bolus dd 1,2 plus 5FU 600 mg/m 2 22-h ic dd1,2 – Q14 days) or FOLFIRI (irinotecan 180 mg/m 2 d1, FA and 5FU as in FOLFOX4, Q 14 days); B 5 mg/kg was administered Q 14 days. The primary end point was Progression Free Survival (PFS). Secondary endpoints included Overall Survival (OS), Response Rate (ORR) and safety. Three hundreds ten events were required to statistically differentiate PFS between groups with 80% power. Results: Between 11/2007 and 03/2012, 376 patients were randomized. Patient characteristics were well balanced between the two arms. FOLFOX4 was used in 60% of the patients and FOLFIRI in 40%. After a median follow up of 18.4 months, 313 progressions and 179 deaths were observed. No statistically significant differences in PFS, OS and ORR were observed (see table). B containg regimens were associated with more frequent hypertension, bleeding, proteinuria and asthenia. Conclusions: The addition of B to a gold standard CT for mCRCdoes not result into an improved prognosis in terms ofPFS, ORR, OS. ITACA’s results (control arm) suggest that the chemotherapeutic schedules used in some of the previously published bevacizumab trials might be suboptimal. Clinical trial information: 2007-004539-44. [Table: see text]