tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemotherpay with gemcitabine plus carboplatin in advanced and unresectable gastric cancer
Authors: C. Leoner, J. Mora, F. Delgadillo, D. Gallardo
Journal: Journal of Clinical Oncology (2005)

4264 Introduction: Gastric cancer is more common in undeveloped countries, the only potentially curative treatment is surgery, a survival of 5–6 months in unresectable disease, neoadjuvant chemotherapy could be useful to achieve surgery. Methods: Patients with unresectable gastric cancer clinical stage III or IV, with normal hematological, renal and liver function, ECOG of 1 or less. Results: 15 patients were included (march 03 to may 04) and treated with gemcitabine 800 mg/mt2 and carboplatin AUC 5 d1 each 21. five ST IIIb, seven ST IV, all with adenocarcinoma, 3 moderated differentiation, 7 poor differentiation; 8 patients had 5 to 6 courses of chemotherapy; in one: four courses; and six two courses; 8 patients had ECOG 1: 9/15 were evaluated for response with endoscopy and CT, we had two complete response; one partial response, four stable disease; two with progression. Five patients with resection after chemotherapy. A total of 60 courses were administrated, we did not have hematological grade 3,4. N/V grade 3: in 5/60 (8.3%). 9.5 median survival in patients with resection vs 1.5 months in patients without resection. Conclusion: This scheme was effective and well tolerated, being possible to resect 33% of the patients, with a better survival (9.5 m) for the patients in whom was possible to achieve resection. No significant financial relationships to disclose.
A phase II study of lapatinib in recurrent or metastatic EGFR and/or ErbB2 expressing adenoid cystic (ACC) and non-ACC malignant tumors of the salivary glands (MSGT)
Authors: M. Agulnik, E. E. Cohen, R. B. Cohen, E. X. Chen, S. J. Hotte, E. Winquist, S. Laurie, D. N. Hayes, J. E. Dancey, L. L. Siu
Journal: Journal of Clinical Oncology (2006)

5566 Background: The limited therapeutic index of chemotherapy in recurrent or metastatic MSGT provides a strong rationale for the evaluation of molecularly targeted agents in this disease. Lapatinib is a dual inhibitor of EGFR and ErbB2 tyrosine kinase activity. Expression of ErbB2 and EGFR has been associated with biological aggressiveness and poor prognosis in MSGT, respectively. We conducted a phase II study to determine the antitumor activity of lapatinib in MSGT. Methods: The main study has a two-stage design in which patients (pts) with progressive, recurrent or metastatic ACC, and immunohistochemically expressing at least 1+ EGFR and/or 2+ ErbB2, were treated with lapatinib 1500 mg PO daily. Each cycle consists of 4 weeks of continuous dosing. Pts with non-ACC MSGT of other histologies, meeting identical eligibility criteria, were treated in this trial as a single-stage, separate cohort. Results: Of 57 pts screened for this study, 29/33 (88%) ACC and 22/24 (92%) non-ACC pts expressed EGFR and/or ErbB2. Thirty-eight pts have been accrued to the study to date (20 ACC/18 non-ACC). The remaining 13 pts who were screened positive either declined entry or were ineligible for other reasons. Baseline data on 34 pts are: M:F = 25:9, median age 56 (range 38–80), PS 0:1:2 = 16:17:1, prior radiation:chemotherapy = 30:18. After 92 cycles of therapy, the most frequent adverse events experienced (as % of cycles) were diarrhea (54%), pain (52%), fatigue (52%), lymphopenia (39%), anemia (38%), hyperglycemia (38%) and dyspnea (34%). No grade 4 adverse events have occurred and only 8 pts experienced a grade 3 adverse event, primarily pain and dyspnea. No significant cardiac toxicity has been observed. Among 14 ACC pts evaluable for response so far: 9 have SD (range 2–9 cycles), 3 PD, and 2 died prior to cycle 2. For 12 evaluable non-ACC pts: 8 have SD (range 2–9 cycles), and 4 PD. No pts have had an objective response. Conclusions: Although there are no objective responses to date, lapatinib is well tolerated, with tumor stabilization achieved by 64% of pts and 24/38 pts remain on treatment at present. Trial accrual of ACC pts into the first stage has been completed, the second stage will open if an objective response is seen. No significant financial relationships to disclose.
Plasma kinetics, uptake by neoplastic breast tissue and preliminary toxicity data of a cholesterol-rich microemulsion (LDE) associated to a paclitaxel (PCT) derivative
Authors: L. A. Pires, R. Hegg, S. R. Graziani, D. G. Rodrigues, R. C. Maranhão, D. F. Deus
Journal: Journal of Clinical Oncology (2006)

12038 Background: Previously we described the association of PCT to a cholesterol-rich microemulsion (LDE) that binds to low-density lipoprotein (LDL) receptors and concentrates in neoplastic tissues. The association is stable, preserves the anti-proliferative activity and reduces the toxicity to animals. The present study was designed to provide preliminary toxicity data on the LDE-PCT oleate formulation, to determine its plasma kinetics compared to that of commercial PCT and to verify the complex ability to concentrate in malignant breast tissue. Methods: To determine the plasma kinetics [ 3 H]-PCT oleate associated to LDE labeled with [ 14 C]-Cholesteryl oleate was intravenously injected into 3 pts and [ 3 H]-commercial PCT into 2 pts 24 h before surgery. Blood samples were collected over the 24 h to quantified radioactivity and the pharmacokinetic parameters. Tumoral and normal breast tissue were excised during the surgery. Other 3 heavily pretreated pts with breast cancer were included in this study to assess toxicity. LDE-PCT (175 mg/m 2 ) was administered as a 1-hour infusion at 3 week interval, without pre medication. Results: Fractional clearance rate (FCR) of LDE and of the drug were similar (0.030 ± 0.026 e 0.018 ± 0.018, respectively, P = 0.5742). The uptake of both [ 14 C]-LDE and [ 3 H]-paclitaxel oleate by breast malignant tissue was 2 and 3 fold greater than that of the normal breast tissue. The PCT oleate T 1/2 (h) was greater than the commercial PCT (T½ = 18.97 ± 7.7 and 7.34 ± 0.40) and the clearence (L/h) of PCT oleate was lesser than the commercial (CL = 1.51 ± 0.18 and 7.95 ± 4.32). No hematological or neurotoxicity was found. Nausea and anorexia grade 1 was found only in one patient. Conclusion: Most of the drug is retained in the microemulsion until its removal from the circulation. The complex is stable and has greater plasma half life and lesser clearance than those for commercial one and can be concentrated in malignant breast tissue. Furthermore, LDE-PCT showed no considerable toxicity events in the 3 patients. Although data regarding response rates were not assessed, our preliminary results suggest that LDE-PCT may be a suitable and powerful weapon to treat breast cancer patients. No significant financial relationships to disclose.
Twelve-year retrospective analysis of lung cancer—The TYROL Study: Daily routine in 1,424 patients (1995–2006)
Authors: M. Fiegl, W. Hilbe, J. Auberger, T. Schmid, T. Auberger, A. Tzankov, W. Sterlacci, H. Denz, H. Jamnig, R. Greil
Journal: Journal of Clinical Oncology (2008)

19063 Background: This retrospective evaluation aimed at analysing features of NSCLC patients´ from diagnosis to surgery up to various numbers of palliative treatment lines within a confined geographic area. These data are of special interest, since basic data like common symptoms of NSCLC are going back to the 70ies and might have changed by the shift of the disease characteristics seen within the last decades. Methods: All patients presented between 1995–2006 at a central cooperative institution (n=1424) were evaluated. Characteristics, such as smoking habits, symptoms leading to diagnosis and co-morbidities, were documented. Furthermore, the individual sequence of all therapies - in curative or palliative intention - was listed, to obtain data on distribution of different therapies and on response and survival. Results: The median age at initial diagnosis was 64.7 years (range, 23–94). 71.4% of patients were males; overall, only 7.3% were never smokers; among women, however, 18.7% were never-smokers (P<0.001). Following symptoms led to initial diagnosis: cough, 57%; hemoptysis, 18%; dyspnoea, 44%; tumor-associated pain, 35%; hoarseness, 3%; elevated temperatures, 10%; night sweats, 20%; loss of weight, 63%. In 21% of patients, diagnosis was by incidence (e.g. check-up). 42% have been treated surgically resulting in median OS of 70.7 months with females having a significantly superior outcome (median OS n.r. vs 59.1 months, p=0.01). Concerning pathological stages, OS in stage I was 107.7 months, stage II 46.4 months, stage IIIA 23.9 and stage IIIB 29.3. 11% of the patients did not receive any kind of therapy. Due to advanced NSCLC patients received chemotherapy in 63%, radiotherapy± chemotherapy in 34% and palliative surgery in 4%. 501 patients received first line chemotherapy with an OS of 9.6 months. Of those, second line chemotherapy was applied in 172 patients (34.3%, OS: 8.4 months), third line systemic therapy in 71 (14%, OS: 8.0 months), fourth line in 26 patients (5%, OS: 5.4 months). Detailed data will be presented at the meeting. Conclusions: This retrospective analysis shows that outcome in daily practice is comparable to that seen in clinical trials. Most importantly, a few selected patients do benefit from subsequent lines of systemic therapies. No significant financial relationships to disclose.
A phase III randomized trial of intensive induction and consolidation chemotherapy ± oblimersen, a pro-apoptotic Bcl-2 antisense oligonucleotide in untreated acute myeloid leukemia patients &gt;60 years old
Authors: G. Marcucci, B. Moser, W. Blum, W. Stock, M. Wetzler, J. E. Kolitz, M. Thakuri, T. Carter, R. K. Stuart, R. A. Larson
Journal: Journal of Clinical Oncology (2007)

7012 Background: Overexpression of Bcl-2, an inhibitor of apoptosis, may render AML cells resistant to chemotherapy and has been associated with unfavorable outcome. Genasense is a phosphorothioate 18-mer antisense oligonucleotide directed against the first 6 codons of Bcl-2. In a phase I study of older (≥60 yrs) AML patients (pts) treated with Genasense in combination with cytarabine (Ara-C) and daunorubicin (DNR) induction and with high-dose cytarabine (HiDAC) consolidation, no antisense-related toxicity was reported. Furthermore, overexpression of Bcl-2 at diagnosis and down-regulation of the Bcl-2 target after antisense treatment was shown in pts achieving complete remission (CR). Methods: A phase III trial (CALGB 10201) randomized untreated older AML pts to induction treatment with Ara-C (100 mg/m 2 /d by CIVI on days 4–10) and DNR (60 mg/m 2 /d on days 4–6) followed by consolidation therapy with HiDAC (2 g/m 2 /d on days 4–8) with (Arm A) or without (Arm B) Genasense (7 mg/m 2 /d CIVI on days 1–10 for induction and days 1–8 for consolidation). The study was powered to identify a survival advantage for pts receiving Genasense. Results: 503 pts enrolled between 12/03 and 10/06; 76 had prior MDS and 24 prior chemoradiotherapy for unrelated cancers. The arms were balanced for age, sex, race, and performance status. No differences in toxicities were observed between the 2 arms. An interim futility analysis performed at 34 months from initiation of the study showed no differences in CR rates (48% vs 52%; p=0.75) or overall survival (OS; p=0.83) between the 2 arms. Estimated OS at 1 yr was 36% for Arm A and 40% for Arm B. Similarly, there were no differences in disease-free survival from date of CR (DFS; p=0.78) or event-free survival (EFS; p=0.77). DFS and EFS rates at 1 yr were 40% and 25% for Arm A, and 43% and 7% for Arm B, respectively. Conclusions: Addition of Genasense to induction and consolidation chemotherapy failed to improve the outcome of older AML pts. Pretreatment levels and post-antisense treatment changes in Bcl-2 expression are now being measured and correlated with outcome. No significant financial relationships to disclose.
How does <sup>18</sup>f-FDG PET-CT scan affect clinical judgment and change treatment decisions in patients with epithelial ovarian cancer?
Authors: F. Selcukbiricik, M. Ozguroglu, M. A. Ozturk, N. Ozgur, H. Turna, D. Tural, M. Hallac, F. Demirkiran, M. Arvas, N. M. Mandel
Journal: Journal of Clinical Oncology (2010)

5053 Background: The aim of the study was to determine the indications of PET-CT assessments in patients with epithelial ovarian cancer (EOC); to find out the concordance ratio of PET-CT results with the results of CT scans and CA-125 levels and finally to determine how PET-CT scan affects clinical judgment and changes treatment decisions. Methods: The files of 540 patients with EOC followed-up between January 2003 and December 2009 in our outpatient clinic were retrospectively analyzed. Among 540, 105 patients were evaluated with at least one PET-CT, with a total number of 116 scans. 80% of patients had serous papillary histology. 61% of patients had one PET-CT whereas 29% had two and 10% had three. 28.5% of PET-CT was done in the first-line treatment course, 39.5% was done in the second line and 16% was done in the third line. Results: The indications for PET-CT imaging were assigned as; isolated high levels of CA-125 (21%), determination of metastatic sites (58%) and presence of discordance between CA-125 levels and CT scan findings (21%). CT scan findings were in concordance with PET-CT in 23% of patients. CT scans determine extra lesions that were negative in PET-CT in only 4% of patients. In 50% of patients PET-CT was more effective to find out lesions that were negative in CT images. The ratio of lesions that were found to be positive in PET-CT but negative in CT scans were as follows; peritoneal implants (43%), intraabdominal lymphadenopathies (31%), intraabdominal solid lesions (21%), hepatic lesions ( 21%), extraabdominal lymphadenopathies (18%). PET-CT was found to change the treatment decisions in 51% of all patients. In the subgroup of patients with isolated CA-125 elevations, PET-CT changed the treatment decisions in 79%. In patients in whom PET-CT was performed before secondary cytoreductive surgery (n = 69), the results of PET-CT changed the treatment choices in 68% of patients. Conclusions: PET-CT is an important tool in the evaluation and management of patients with EOC. Especially in patients with isolated CA-125 elevation and patients planning to undergo secondary cytoreductive surgery, PET-CT is complimentary to CT scan and has an impact on clinical judgment and treatment decisions. No significant financial relationships to disclose.
Phase II study of gemcitabine and docetaxel as first-line chemotherapy in locally advanced/metastatic leiomyosarcoma
Authors: B. M. Seddon, M. R. Scurr, R. L. Jones, Z. Wood, C. Propert-Lewis, R. A'Hern, J. S. Whelan, I. R. Judson
Journal: Journal of Clinical Oncology (2009)

10528 Background: Locally advanced/metastatic soft tissue sarcoma is invariably incurable with a poor prognosis. Recently gemcitabine and docetaxel have been shown to be active in pre-treated relapsed leiomyosarcoma. This study aims to investigate the combination as first line treatment in patients with unresectable incurable leiomyosarcoma. Methods: Patients received gemcitabine 900mg/m 2 days 1 and 8, and docetaxel 100mg/m 2 day 8, administered 3-weekly for up to 8 cycles, with GCSF support on days 9–15. Patients who had received previous radiotherapy were treated at 75% dose. Patients were evaluated for response by RECIST after cycles 2, 4, 6, and 8, and three-monthly after completing treatment. The study was conducted with a Simon 2-stage design, recruiting 19 patients in stage 1, and 25 patients in stage 2. The primary endpoint was response rate, and secondary endpoints progression free survival (PFS), overall survival (OS), and toxicity evaluation. Results: Forty-four patients were treated. Eligible patients had histologically proven leiomyosarcoma of the uterus (48.9%) or other sites (51.1%) unresectable for cure, with measurable disease, no previous chemotherapy, adequate organ function, and performance status 0–2. 84.4% had metastatic disease, and 15.6% had locally advanced disease. 11% of patients had grade 1 disease, and 89% had grade 2/3 disease. All patients had demonstrated disease progression prior to trial entry. Responses were as follows: partial response 12 (27%), stable disease (confirmed) 16 (36%), stable disease (unconfirmed) 5 (11%), progressive disease 11 (25%). Median OS and PFS were 578 (95% CI 131–322) and 216 (95% CI 24–169) days. Progression free rates at 3 and 6 months were 68.9% (95% CI 55.1–82.7%) and 57.8% (95% CI 43.1–72.5%). Conclusions: This study demonstrates gemcitabine and docetaxel to be active in leiomyosarcoma in the first line setting. Further investigation comparing the combination with current standard therapies for leiomyosarcoma is warranted. No significant financial relationships to disclose.
Evaluation of guilt, shame and depression in non-small cell lung cancer (NSCLC) relative to breast (BC) and prostate cancer (PC)
Authors: N. K. Schmidt, N. M. Else-Quest, L. Hammes, J. Eickhoff, J. Hyde, J. H. Schiller
Journal: Journal of Clinical Oncology (2006)

7158 Background: Most NSCLC is related to smoking, and thus is potentially avoidable. Prior qualitative studies suggest that stigma from a self-induced illness results in feelings of guilt and shame in NSCLC patients (pts). This study is a prospective quantative study of guilt, shame and depression in NSCLC pts relative to BC and PC pts. Methods: Stage IV NSCLC, BC, and PC pts completed 3 surveys over 6 months (T1–3). The survey was a 20 minute questionnaire, including standardized tests of shame, guilt, and depression, as well as several investigator designed questions (IDQ) and demographic data. Goal enrollment is 94 NSCLC pts, 47 BC pts and 47 PC pts, with 80% power to detect a 0.75 point difference in the State Shame and Guilt Scale (SSGS, scores 1 to 5). Data for the first 159 pts with T1 and T2 data are presented. Means of the pooled results for the SSGS and IDQ were compared via analysis of variance; impact of cancer (CA) and gender were performed via regression analyses. Results: 92 NSCLC, 41 PC, and 26 BC patients have been enrolled. 55% of participants are male, mean age is 66 years (35–87), and 67% are married. There is a diverse range of incomes and education. IDQ were combined into a composite score, “self-blame” (reliable, internal consistency score 0.76). Results at T2 are presented in the table. Multiple regression analysis performed on women found that type of CA predicted depression, mediated by shame and guilt. Conclusions: NSCLC is associated with increased levels of guilt and shame leading to depression, relative to BC and PC. This disparity is particularly striking amongst women with NSCLC. Guilt, shame and depression may hamper a pt’s ability to advocate for themselves and may affect treatment outcomes. Further investigation is warranted as to whether a targeted intervention may improve levels of stigma amongst NSCLC pts. Funding provided by an American Medical Association Seed Grant. [Table: see text] No significant financial relationships to disclose.
A phase II trial of sunitinib and gemcitabine in sarcomatoid and/or poor-risk patients with metastatic renal cell carcinoma.
Authors: Rana R. McKay, Toni K. Choueiri, Lillian Werner, Michael B. Atkins, Kara M. Olivier, Jiaxi Song, Sabina Signoretti, David F. McDermott, M Dror Michaelson
Journal: Journal of Clinical Oncology (2015)

408 Background: Sarcomatoid renal cell carcinoma (sRCC) is associated with aggressive biology and poor prognosis. Poor-risk RCC, as defined by established risk factors, demonstrates similar aggressive behavior. Though vascular endothelial growth factor (VEGF) therapy is the standard initial therapy for RCC, insufficient data exist in sRCC and efficacy is limited in poor-risk disease. The objective of this study was to investigate the efficacy of anti-angiogenic therapy and cytotoxic chemotherapy in clinically aggressive RCC. Methods: We conducted a phase II single arm trial at 3 institutions of sunitinib (37.5 mg PO daily, 2-weeks on, 1-week off) and gemcitabine (1,000 mg/m 2 IV day 1 and 8 of every 21-day cycle) in patients (pts) with sarcomatoid or poor-risk RCC (NCT00556049). The primary endpoint was objective response rate (ORR) defined by RECIST. Secondary endpoints included overall survival (OS), safety, and biomarker correlatives. Results: Overall, 39 pts had sRCC and 33 had poor-risk RCC. Of the 32 sRCC pts with evaluable disease, the ORR was 26% (n=10) and stable disease rate (SDR) was 38% (n=15). Of the 31 evaluable poor-risk RCC pts, ORR was 24% (n=8) and SDR was 39% (n=13). OS for pts with sRCC was 10 months (95% CI 6, 24) and 15 months (95% CI 9, 29) for pts with poor-risk RCC. The most common ≥ grade 3 treatment-related adverse events included neutropenia (n=20), anemia (n=10), and fatigue (n=7). Of the 27 sRCC pts with tissue for central review, increased sarcomatoid histology (&gt;10%) correlated with an improved clinical benefit rate (CBR, ORR + SDR) compared to pts with ≤10% sarcomatoid histology (CBR 100% for &gt;10% versus 55% for ≤10% sarcomatoid, p=0.04), suggesting that sRCC was sensitive to combination therapy. Pts with clear-cell histology were more likely to experience an OR compared to those without clear-cell histology (32% versus 16%, p=0.23). Of 11 pts with tumor DNA sequencing data, no actionable gene mutations were identified. Conclusions: Our results suggest that VEGF targeted therapy and cytotoxic chemotherapy are an active combination in pts with rapidly progressive RCC. The combination may be more efficacious than either therapy alone and this is under further investigation (NCT01164228). Clinical trial information: NCT00556049.
Angiogenesis index (AI) as a predictor of tumor burden in lymph nodes in colon cancer (Cca) patients (pts) undergoing sentinel lymph node (SLN) mapping (M)
Authors: S. Grewal, S. Saha, M. Patel, R. Sehgal, R. Parker, E. Mechetner, D. Wiese, B. Yestrepsky, C. Yee, K. Barber
Journal: Journal of Clinical Oncology (2007)

14509 Background: Lymph Node (LN) status is the most important prognostic factor in colon cancer (Cca). Angiogenesis Index (AI) has been studied as a prognostic marker in various solid tumors with conflicting results. Hence, a retrospective analysis was done to evaluate the role of AI as a prognostic marker in Cca. Methods: Pts with Cca who underwent SLNM to determine LN status were included. A portion of tumor was sent for tumor marker analysis including p53, Thrombospondin-1 and CD31 by IHC. AI was derived for each specimen by summing the biomarker specific score for the three tumor markers. AI of -ve 6 was taken as cut off for significance based on previous studies on solid tumors. Metastatic foci in SLNs and non-SLNs were measured in greatest diameter by ocular micrometer; and were added for each pt to estimate overall tumor burden in SLNs and non-SLNs. Results: A total of 111 consecutive pts with Cca were included in the study. SLNM was successful in 100% pts. Pts with distant metastasis (mets) (n=18), Tis (n=1) and skip mets (n=9) were excluded from final analysis. Out of the remaining 83 pts, an AI of -6 or less was found in 22 pts (26.5%) while 61 pts (73.5%) had AI of more than (&gt;) -6. Of the 61 pts with AI &gt; -6, 37.7% pts were SLN +ve while 62.3% pts were SLN -ve (p=0.05)( Table 1A ). Of the 22 pts with AI less than or -6, 45.5% pts were SLN +ve and 54.5% pts were SLN -ve (p=0.65). Size of the metastatic tumor burden in lymph nodes was available in 69.7% of SLN +ve pts. Total average tumor burden for pts with AI &gt; -6 (n=15) was 2.04cm as compared to 1.48cm in pts with AI of -6 or less (n=8)(p=0.66). Average SLN met size was 0.73cm in pts with AI &gt; -6 and 0.63cm in pts with AI of -6 or less (p=0.66)( Table 1B ). Conclusions: AI did not correlate with nodal positivity or tumor burden in LNs in pts with Cca. LN status remains the most important prognostic marker in Cca. Further larger trials are required to determine the role of AI as a prognostic marker in Cca. [Table: see text] [Table: see text] No significant financial relationships to disclose.