tbuckley/cabot-search huggingface dataset:
A phase II study of oral mammalian target of rapamycin (mTOR) inhibitor, RAD001 (everolimus), in patients with recurrent endometrial carcinoma (EC)
Authors: B. M. Slomovitz, K. H. Lu, T. Johnston, M. Munsell, L. M. Ramondetta, R. R. Broaddus, R. L. Coleman, C. Walker, D. M. Gershenson, T. W. Burke, J. Wolf
Journal: Journal of Clinical Oncology (2008)

5502 Background: The finding of PTEN mutations in 40–60% of EC suggests this pathway is important in the pathogenesis of this disease. Loss of PTEN leads to constitutive activation of AKT, which leads to up-regulation of mTOR. RAD001 is an oral rapamycin analog that acts by selectively inhibiting mTOR. Methods: A single institution, open-labeled, single arm, Phase II study in patients with recurrent EC who have failed at least one and no more than 2 prior chemotherapeutic regimens was performed. RAD001 was administered at a dose of 10 mg PO daily for 28 day cycles. One dose reduction (to 5 mg) was permitted. Patients were treated until progression or toxicity. The primary efficacy endpoint is Clinical Benefit Response (CBR), defined as a complete or partial response or prolonged stable disease (SD;>8 weeks) by RECIST criteria. Inclusion was limited to patients with endometrioid EC. Correlative studies evaluating PTEN were performed if tissue was available. Results: Twenty-nine patients were enrolled (median age 58; range: 38–81). A total of 74 cycles have been administered. 11 of 25 (44%) evaluable patients for response had CBRs. All of these patients had SD (median: 4 cycles; range 2–10). One patient achieving CBR is still on treatment. Patients with CBR discontinued treatment because of toxicity(6), progression(3), and noncompliance(1). 14 of the 25 patients discontinued treatment after receiving ≤2 cycles because of progressive disease (13) and toxicity (1). Four patients were inevaluable after receiving ≤1 cycle because of toxicity (3) or noncompliance (1). The most common adverse events were abdominal pain (28%), nausea/vomiting (21%), low grade fever (21%), and anemia (17%). 12 patients required a dose reduction. Fifteen of 25 evaluable patients had tissue available from the original hysterectomy. Loss of PTEN expression was predictive of CBR with a sensitivity of 88%, specificity of 57%, positive predictive value of 70% and negative predictive value of 80% (P=0.10). Conclusion: RAD001 shows encouraging single agent clinical benefit in pretreated patients with recurrent EC. Loss of PTEN may predict CBR. Future studies will evaluate this agent in combination with hormonal and/or cytotoxic therapy. No significant financial relationships to disclose.
The international prognostic index at relapse predicts autologous stem cell transplantation outcome for aggressive non-Hodgkin's lymphoma in second remission or chemosensitive first relapse
Authors: R. E. Lerner, D. J. Weisdorf, J. S. Miller, P. B. McGlave, L. J. Burns
Journal: Journal of Clinical Oncology (2004)

6661 Background: Autologous stem cell transplantation (ASCT) has become the standard treatment for patients with relapsed aggressive non-Hodgkin's lymphoma (NHL) responding to conventional salvage chemotherapy. Nevertheless, greater than half of these patients will relapse and ultimately die. The international prognostic index (IPI) was developed to identify patients with aggressive NHL who have different risks for death. The objective of the present study was to investigate the prognostic value of the IPI at relapse for patients with aggressive NHL undergoing ASCT. Methods: Eighty patients, median age 47 years (range 19–68 years), with aggressive NHL (diffuse small, mixed, and large cell, immunoblastic, and anaplastic B-cell) in second complete remission (CR, n = 50) or first chemosensitive relapse (n = 30) were treated between 1984 and 2002 with ASCT. Clinical features predictive of overall survival (OS) and progression-free survival (PFS) were analyzed. Results: Post ASCT, CR was achieved in 73 patients (91%). With a median follow-up of 5 years (range 205 days to 14 years), OS and PFS at 5 years were 37% (95% CI 26–48) and 37% (95% CI 26–48), respectively. Two risk groups with significantly different OS and PFS were identified by the IPI at relapse. The high-risk group (3, 4, or 5 IPI factors) had 3.2 times (95% CI 1.5–6.6, p = .002) the risk of death and 3.5 times (95% CI 1.6–7.3, p = .001) the risk of relapse as the low-risk group (0, 1, or 2 IPI factors). In Cox regression analysis, high-risk IPI status (RR 3.8, 95% CI 1.7–8.4, p = .001) and bone marrow (BM) involvement at diagnosis (RR 2.9, 95% CI 1.3 - 6.3, p = .009) were independent predictors for poor OS. Similarly, high-risk IPI status (RR 3.9, 95% CI 1.8–8.7, p = .001) and BM involvement (RR 4.2, 95% CI 1.8–9.4, p = .001) were independent predictors for poor PFS. Conclusions: The IPI at relapse predicts OS and PFS following ASCT for patients with aggressive NHL in second remission or chemosensitive first relapse. Patients with high-risk IPI status at relapse should be considered for novel therapeutic approaches. No significant financial relationships to disclose.
Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.
Authors: Li-Tzong Chen, Daniel D. Von Hoff, Chung-Pin Li, Andrea Wang-Gillam, Gyorgy Bodoky, Andrew Peter Dean, Yan-Shen Shan, Gayle S. Jameson, Teresa Macarulla, Kyung-Hun Lee, David Cunningham, Jean-Frédéric Blanc, Richard Hubner, Chang-Fang Chiu, Gilberto Schwartsmann, Jens T Siveke, Fadi S. Braiteh, Victor M. Moyo, Bruce Belanger, Eliel Bayever
Journal: Journal of Clinical Oncology (2015)

234 Background: MM-398 is a nanoliposomal encapsulation of irinotecan. OS in the ITT population was significantly longer with MM-398+5FU/LV over 5FU/LV alone, and the most frequent grade 3+ AEs included neutropenia, fatigue, and GI effects (diarrhea and vomiting). Expanded, pre-specified analyses of the Phase 3 study are presented. Methods: Patients (n=417) with mPAC previously treated with gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m 2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m 2 over 24 h) plus racemic leucovorin (LV) (200 mg/m 2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m 2 IV over 90 min) prior to 5FU (2,400 mg/m 2 over 46 h) and racemic LV (400 mg/m 2 over 30 min) q2w. The primary endpoint was OS. The Intent To Treat (ITT) population included all randomized patients; the Per Protocol (PP) population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria. Results: Analysis of the PP populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination MM-398+5FU/LV arm over the control 5FU/LV arm. The MM-398 monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9 levels, consistently favored OS for the MM-398+5FU/LV arm over the 5FU/LV arm. Conclusions: Expanded analysis of the PP population and sensitivity analyses support the favorability of MM-398+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506. [Table: see text]
The use of palliative sedation for intractable symptoms in a palliative care unit (PCU) in a comprehensive cancer center
Authors: A. Elsayem, E. Curry, J. Boohene, H. Ibrahim, E. Pace, S. Hung, E. Bruera
Journal: Journal of Clinical Oncology (2006)

8577 Background: There is wide variation in the frequency of reported use of palliative sedation (PS) to control intractable and refractory symptoms. Institutions have established policies for midazolam infusion in cases of PS. The indications and outcomes of this procedure have not been well characterized Methods: Our midazolam policy for PS requires 1:1 nursing for the first 24 hours and documentation of discussions regarding sedation. We reviewed our PCU database for all admissions for the first 11 months of 2005. We used pharmacy records for all patients who received medications used for sedation (chlorpromazine, lorazepam, midazolam). We reviewed all charts of pts who received any of these drugs to establish if the indication had been PS. Results: 148/484 admissions died in the PCU [31%]. 65/484 admissions (13%), and 47/ 148 patients who died (32%) received PS. Median age of patients (pts) was 58, 42 pts were male [65%], and the most frequent primaries observed were lung 24 [37%], hematologic 12 [18%], head and neck 7 [11%], and gastrointestinal 7 [11%]. Results are indicated in the table. * 2 patients had more than one indication for sedation The main causes for PS in our patients were delirium 57 [88%], dyspnea 6 [9%], and bleeding 4 [6%]. 18/65 patients who received PS [35%] were discharged alive, versus 318/419 [76%] who did not receive PS [p&lt; 0.001]. Midazolam was used in 11/65 episodes [17%]. 4/6 pts with PS for dyspnea received midazolam [66%], versus 8/57 with PS for delirium or bleeding [14%], p=0.01]. 18/54 pts who received PS using other drug were discharged alive [33%], versus 0/11 pts who received midazolam [p=0.02]. Conclusions: Palliative sedation was required in 32% of pts who died in the hospital. Reporting midazolam utilization rates for monitoring overall PS outcomes, results in significant under reporting. Midazolam was used more frequently in cases of progressive dyspnea and poor prognosis. Less restrictive policies in the use of midazolam may result in more use for PS. Data accrual continues. [Table: see text] No significant financial relationships to disclose.
Docetaxel plus cisplatin versus vinorelbine plus cisplatin as adjuvant chemotherapy in stage IB-IIIA non-small cell lung cancer: Preliminary result of phase II pilot trial CHL001/TAX622.
Authors: D. Chu, G. Wu, B. Han, X. Song, G. Chen, C. Zhou, Q. Wang, S. Wu, Y. Wang, W. Zi-Ping
Journal: Journal of Clinical Oncology (2010)

7063 Background: Adjuvant chemotherapy has become a standard of care for patients with completely resected stage IB, II and IIIA non-small cell lung cancer (NSCLC). However, few data exist comparing the efficacy of vinorelbine/cisplatin and docetaxel/cisplatin regimens for adjuvant treatment of NSCLC. Methods: Patients with stage IB, II and IIIA NSCLC who underwent curative resection were randomly assigned to arm A: docetaxel (75 mg/m2, day1) and cisplatin(75 mg/m2, day1) (DP) or arm B: vinorelbine (25 mg/m2, day 1, 8) and cisplatin(75 mg/m2, day1) (VP) for 4 cycles each. Both regimens were repeated every 3 weeks. Primary end point is disease free survival (DFS); secondary end points are safety, and quality of life (QOL). Results: 158 patients were enrolled between Dec 2005 and Nov 2008, 15 patients withdrew after randomization. As of this report, data of 143 patients was analyzed (82 from DP arm and 61 from VP arm). Patient demographics(DP/VP): median age 56.2/55.9 years; 70.7%/70.5% male; 54.1%/43.3% adenocarcinoma, 32.9%/40.0% squamous cell carcinoma, 2.4%/6.7% large cell carcinoma; 91.3%/86.9% lobectomy, 6.3%/9.8% pneumonectomy, 2.5%/3.3% wedge resection. The stage distribution was: 43.9%/44.3% IB, 11.0%/3.3% IIA, 13.4% /21.3% IIB, 31.7% /31.1% IIIA. Relative dose intensity of docetaxel/cisplatin was 95.1%/95.0% and vinorelbine/cisplatin 94.5%/95.3%. Significant difference for treatment adjusting: DP/VP (84.1% vs 96.7%, p=.015) e.g. dose reduction (15/13), administration delay (55/49), or treatment withdrawal (3/12). Main toxicities (DP/VP): neutropenia (61.0%/57.4%, p=.66), fatigue (46.3%/54.1%, p=.36), nausea (53.7%/65.6 %, p=.15), alopecia (61.0%/11.5%, p=.0001). Significantly fewer patients reported alopecia in VP arm. With median follow up 20 months, disease free rate was 70.1%/71.4% (p=.88), survival rate was 87.7% /81.8% (p=.37) for DP/VP arm respectively. Conclusions: Preliminary results indicate that both docetaxel plus cisplatin and vinorelbine plus cisplatin regimens as adjuvant therapy are feasible and effective for Chinese patients. Long-term follow-up data will be analyzed in the future. No significant financial relationships to disclose.
Current U.S. physician practices and attitudes in the treatment of peripheral T-cell lymphoma (PTCL).
Authors: L. C. Pinter-Brown, R. P. Stephan
Journal: Journal of Clinical Oncology (2010)

e18546 Background: PTCLs are a group of rare lymphomas with a poor prognosis (5-yr OS <25%). As the best treatment practices are unclear, we sought to identify the current treatment practices and their rationale. Methods: Internet-based surveys were sent to U.S.- based hematologic and medical oncologists to determine the representative treatment practices and attitudes in PTCL. 138 complete responses (79% male) from 33 states were received from oncologists active in PTCL treatment (4.1% response rate). Results: Chemotherapy, single or multi-agent, is the most common treatment selection for upfront therapy in early and advanced disease. IPI score has little or no effect on treatment selection. Treatment practices for relapsed and refractory disease are similar to each other. CHOP is the most commonly used first-line drug treatment regimen for PTCL. ICE/DHAP/ESHAP is preferred for refractory and at first relapse, but no clear consensus exists for the second relapse. Only one-third of PTCL patients participate in clinical trials at any stage in their course (Table). While 35% of oncologists consider BMT as treatment option. this modality is actually utilized far less. Overall usage of BMT in PTCL ranged from 8.1-11.4% of patients, depending on disease stage and IPI score. The oncologists' choices were driven by efficacy and the safety/tolerability profile chosen regimen. Conclusions: Most oncologists are treating PTCL with some type of systemic drug therapy, typically a multidrug regimen. CHOP is the “standard of care” for upfront therapy but a common standard from relapsed or refractory disease could not be identified. As CHOP is not as successful when applied to the treatment of patients with PTCL, participation in clinical trials should be encouraged both in the up-front and relapsed/refractory settings. Most commonly used chemotherapeutic regimens for PTCL CHOP ICE/DHAP/ESHAP EPOCH/HyperCVAD Clinical trial Early (I/II) 55.8% 2.5% 4.2% 4.2% Advanced (III/IV) 48.1% 6.1% 17.6% 6.1% Refractory 3.9% 31.5% 21.3% 13.4% Relapsed (1st) 1.6% 36.8% 12.8% 11.2% Relapse (2nd) 2.6% 13.1% 4.9% 32.8% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MDOutlook, LLC Allos Therapeutics, MDOutlook, LLC Allos Therapeutics
Fractional weekly administration of irinotecan and cisplatin as a second-line treatment for advanced gastric cancer
Authors: H. C. Jeung, S. H. Noh, J. I. Lee, H. C. Chung, S. Y. Rha, J. K. Roh
Journal: Journal of Clinical Oncology (2005)

4079 Background: We assessed the efficacy and safety of the weekly irinotecan and cisplatin combination to the patients who had failed with one previous chemotherapy for advanced gastric cancer. Methods: Patients with measurable lesion and adequate hepatic, renal, and bone marrow functions were eligible for entry. Chemotherapy consisted of 50 mg/m2 irinotecan and 30 mg/m2 cisplatin, both administered intravenously a day per week for 3 consecutive weeks, followed by a recovery period of 1 week. The response rate, time to progression (TTP), survival and toxicity profile were analyzed. Results: All enrolled 33 patients were assessable, and the median relative dose intensity of previous chemotherapy was 0.86. Total 131 cycles were administered and median number of cycles per patient was 4. Of 393 doses, 171 doses (44.3%) were delayed or missed, and the median relative dose intensity was 0.79 for the both agents. Six patients (18.1%) showed objective tumor response including 1 complete response. The median time to progression was 19 weeks (range: 4–61+ weeks), and the median survival time was 39 weeks (range: 3–96+ weeks). The 1-year survival rate was 30.3%. Major toxicicity included neutropenia (Grade III-IV 36.4%), vomiting (15.2%) and anorexia (15.2%). There was no treatment-related mortality. Pretreatment level of CA19–9 and dose intensity were the factors influencing TTP (p=0.035, 0.045, respectively). Seventeen patients (51.5%) could proceed to next-line chemotherapy without deterioration of performance status. Conclusions: We concluded that the combination of irinotecan and cisplatin is feasible with moderate activity for patients with advanced gastric cancer as a second-line palliative treatment. A modification in doses and schedules may be warranted to obtain adequate dose intensity to maximize treatment effect. No significant financial relationships to disclose.
MERIT: Analysis of differential gene expression in patients (pts) with advanced non-small-cell lung cancer (NSCLC) treated with erlotinib
Authors: P. Delmar, E. H. Tan, A. G. Pluzanska, R. Ramlau, M. Reck, P. McLoughlin, J. Baselga
Journal: Journal of Clinical Oncology (2008)

8046 Background: Erlotinib significantly prolongs survival of pts with previously treated advanced NSCLC. No reliable criteria have been established that allow selection of those pts most likely to benefit from erlotinib therapy. The primary objective of the multi-center, open-label phase II MERIT study was to identify markers ‘highly’ predictive of clinical benefit with erlotinib. Methods: Eligible pts had stage IIIb/IV NSCLC, ECOG PS 0–2, had failed ≥1 chemotherapy regimen (or refused/were unsuitable for chemotherapy), and were willing to undergo a tumor biopsy via bronchoscopy before starting treatment. Erlotinib (150 mg/day p.o.) was given until disease progression (PD) or unacceptable toxicity. Clinical benefit was defined as objective response or stable disease lasting ≥12 weeks (according to RECIST). Fresh-frozen biopsies were analysed using gene expression profiling. Other analyses, including EGFR FISH, IHC and mutation detection were also performed. Results: 264 pts were recruited at 26 centers in 12 countries. Gene expression profiles from 102 pts treated with erlotinib were suitable for statistical analyses. The primary analysis, comparing benefiting and non-benefiting pts, did not identify statistically significant genes after correction for multiple testing. An exploratory analysis, comparing pts who had objective response (n=6) with pts who had PD or no assessment available (n=65), identified three differentially expressed genes, all on chromosome 7: EGFR, PSPH (closely collocated to EGFR) and RAPGEF5. qRT-PCR is being performed on the same samples to confirm these findings; the results from this and further exploratory analyses will be presented. Research regarding the specific functions of the detected genes is also ongoing. Conclusions: MERIT is the largest prospective gene profiling biomarker trial ever conducted in advanced NSCLC. Results from the primary analysis show that ‘highly’ predictive markers of clinical benefit are unlikely to exist. In an exploratory analysis, three genes were found to be associated with response, and further evaluation of these genes is warranted in prospectively defined, randomized clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Boehringer Ingelheim, Lilly Oncology, Roche AstraZeneca Oncology, Bayer, Boehringer Ingelheim, Lilly Oncology, Pierre Fabre, Roche Roche
Chemopreventive effect of the aromatase inactivator exemestane in the dimethylbenzanthracene (DMBA)-induced mammary tumors in rats
Authors: E. Di Salle, T. Zaccheo, R. Rossi, E. Pesenti
Journal: Journal of Clinical Oncology (2004)

3108 Background: Exemestane (E, Aromasin) is an aromatase inactivator indicated for the treatment of advanced breast cancer (BC) and under evaluation for early BC. Methods: We have investigated the chemopreventive effect of E in the DMBA-induced mammary tumor in rats, an estrogen-dependent BC model. Tumors were induced by a single oral dose of DMBA (20 mg/rat). One week later animals were divided in five groups (20–22 animals/group): controls, E given weekly IM as a depot formulation at three dose levels (4, 20 or 100 mg/kg/week for 19 weeks) and ovariectomy (OVX). Control and OVX animals received the correspondent vehicle given IM, weekly for 19 weeks. Animals were palpated for tumor formation every week. Results: The final body weight was unchanged at the two lower E doses and increased by 26% and 21% for E 100 mg/kg/week and OVX, respectively. The results on tumor incidence, multiplicity (mean number of tumor per rat), tumor burden and uterus weight are reported in the Table. At the highest dose of 100 mg/kg/week E markedly reduces tumor incidence, multiplicity and burden at the end of the study period, similarly as effective as OVX. E causes a slight reduction in uterus weight only at the intermediate dose of 20 mg/kg/week. Conclusions: These data indicate that E is an active BC chemopreventive agent in an animal model. A 3-arm chemoprevention study using E +/- celecoxib vs placebo in post-menopausal women at risk is underway. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacia Italia
Improved survival in patients with hepatocellular carcinoma over 30 years in Japan: Analysis of nationwide prospective registry of 148,161 patients.
Authors: M. Kudo, N. Izumi, N. Kokudo, M. Sakamoto, Y. Matsuyama, T. Ichida, O. Nakashima, O. Matsui, Y. Ku, M. Makuuchi
Journal: Journal of Clinical Oncology (2011)

4054 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer death in the world. To our best knowledge, only few nationwide survival data is available; USA (SEER Database), Japan and Korea. Liver Cancer Study Group of Japan started nationwide registry along with follow-up survey since 1965. In this report we analyzed improvement of overall survival (OS) in patients with HCC in Japan. Methods: We analyzed follow-up data of 148,161 HCC patients who were prospectively registered between 1978-2005 and analyzed the OS according to 5-year interval. Results: The 5-year overall survival rate was found to be 5.1% in patients who registered in the period A (1978-1980), 13.9% in the period B (1981-1985), 24.9% in the period C (1986-1990), 32.0% in the period D (1991-1995), 38.8% in the period E (1996-2000) and 42.7% in the period F (2001-2005). Median survival time (MST) was found to be 4, 16, 26, 36, 44, and 50 months in the period A, B, C, D, E, and F, respectively. All of OSs in resection, ablation, TACE, and transarterial infusion chemotherapy (HAIC) were also significantly improved period by period. The latest 5-year survival rate of 42.7 % is much better than that of 13 % in United States in the same period according to American Cancer Society Annual Report in 2010 and 18.2% in Korea according to Korean Cancer Registry Database. This drastic improvement of OS in HCC patents in Japan is attributed to the introduction of nationwide surveillance program in 1980, nationwide establishment of resection and TACE procedure in 1985, and invention of ethanol injection therapy in 1990, introduction of HAIC for advanced HCC and introduction of radiofrequency ablation in 2000. Conclusions: Overall survival in patients with HCC in Japan was much improved from MST of 4 to 50 months over 30 years, which may be the best in the world. Further improvement in OS will be expected by the introduction of molecular targeted agents, such as sorafenib and other agents under clinical trials.