tbuckley/cabot-search huggingface dataset:
Chemotherapy with carboplatin - paclitaxel as the only adjuvant treatment in uterine papillary serous and clear cell carcinoma
Authors: G. Bozas, E. Kastritis, A. Rodolakis, G. Vlahos, C. Papadimitriou, S. Markaki, D. Gika, A. Bamias, M. A. Dimopoulos
Journal: Journal of Clinical Oncology (2005)

5164 Background: Papillary serous (UPSC) and clear cell (UCCC) carcinomas of the uterine corpus represent more aggressive tumors than the more common endometroid cancer and exhibit a propensity for extrapelvic metastasis. We investigated the activity and safety of paclitaxel plus carboplatin as the only adjuvant treatment in patients with surgically resected UPSC and UCCC. Methods: Fifteen patients with stage IB-IV UPSC or UCCC were treated with a mean of 6 courses of paclitaxel 175mg/m2 plus carboplatin AUC 5 at three week intervals, after undergoing surgery with curative intent. No patient underwent pre- or post- chemotherapy irradiation. Results: With a median follow-up of 29.4 months, 6 patients (40%) relapsed and two (13.3%) died of disease. Mean time to recurrence was 16.9 months. Recurrence rate per stage was 17% (n=1/6) for stage IB/C, 57% (n=4/7) for stage IIIA/C and 50% (n=1/2) for stage IV. All relapses were abdominopelvic except for one case, where pelvic recurrence was accompanied by lung metastasis. The treatment was well tolerated with no life-threatening events and no persistent toxicities. The most frequent grade 3–4 toxicity was neutropenia (53%) but there was only one case of febrile neutropenia (6.6%). Conclusions: Adjuvant chemotherapy with paclitaxel and carboplatin is feasible and probably reduces the risk of hematogenous metastasis in surgically treated UPSC and UCCC. No significant financial relationships to disclose.
Phase I study of sapacitabine, an oral nucleoside analogue, in patients with advanced leukemias or myelodysplastic syndromes
Authors: W. Plunkett, G. Garcia-Manero, S. Faderl, J. Cortes, P. Boone, C. Hilbe, S. Green, J. H. Chiao, H. Kantarjian
Journal: Journal of Clinical Oncology (2007)

7063 Background: Sapacitabine, a 2′-deoxycytidine nucleoside analogue with unique ability to induce G2 cell cycle arrest and cause irreparable single-strand DNA breaks, is undergoing clinical evaluation for the treatment of cancer. The recommended Phase II dose (RD) in patients with advanced solid tumors was 75 mg b.i.d.×7 days orally every 21 days. The major DLT was myelosuppression. Here, we present the initial results of a Phase I study of sapacitabine in patients with advanced leukemias or MDS. The primary objective was to define the MTD of the above dosing schedule and the secondary objectives were to characterize the PK/PD effects of sapacitabine and its major metabolite CNDAC. Methods: Eligible patients had relapsed/refractory leukemias or MDS, or untreated disease if not willing to proceed with conventional systemic chemotherapy, adequate organ functions and performance status of 0–2. At least 3 patients were enrolled at each dose level. The MTD was the highest dose level at which =2/6 patients experienced a DLT during the first treatment cycle. Results: Twenty- nine patients received sapacitabine. Median age was 64 (range: 36 - 91). The majority of patients had AML (n=24) or MDS (n=4). Median number of prior chemotherapies was 2 (range: 0 - 6). MTD was reached at the dose level of 375 mg b.i.d. with 2/7 patients experienced the DLT of small bowel obstruction (n=1) or neutropenic colitis (n=1). One patient died from complications of neutropenic colitis. Common non-hematologic adverse events (all grades, regardless of causality) included nausea, vomiting, diarrhea, anorexia, alopecia, and fatigue, most of which were mild to moderate in intensity. PK and PD data are being analyzed. To date, 7 patients (5 AML, 2 MDS) had a reduction in bone marrow blast counts to = 5% including 1 CR in refractory AML with incomplete platelet recovery and 1 CR in relapsed MDS. In addition, 2 AML patients with relapsed leukemia cutis had a significant reduction in leukemia infiltrates in skin. Conclusion: The RD of sapacitabine for the b.i.d.×7 days every 21 days schedule is 325 mg b.i.d. The DLT is gastrointestinal toxicity. Sapacitabine is well tolerated and has promising antileukemic activity in patients with relapsed or refractory AML and MDS. No significant financial relationships to disclose.
Increased incidence of brain metastases in ERCC1-negative NSCLC patients treated with adjuvant cisplatin-based chemotherapy
Authors: B. Besse, C. Massard, V. Haddad, F. André, A. Dunant, R. Pirker, K. A. Olaussen, E. Brambilla, P. Fouret, J. Soria
Journal: Journal of Clinical Oncology (2007)

7581 Background: We have recently demonstrated that ERCC1 is a predictor of the benefit of cisplatin-based adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC). Non-squamous carcinomas have an increased risk of brain metastases (BM). Since brain is considered as a sanctuary site for chemotherapy, we hypothesised that there was an increased incidence of BM in ERCC1- negative non-squamous NSCLC patients treated with adjuvant cisplatin-based chemotherapy. Methods: Incidence of BM and histo- clinical parameters were analyzed in a population of 783 patients enrolled in the IALT trial. A subgroup analysis was performed in ERCC1 negative non-squamous NSCLC patients. Results: One hundred and one patients out of 783 (13%) developed BM alone or in association with other metastatic sites. In multivariate analysis, the clinical parameters associated with the occurrence of BM were nodal status (p=0.02), histological type (p=0.001) and pleural invasion (p=0.02). There is no effect of chemotherapy on BM (HR 1.38 [0.91–2.07], p=0.13). In patients with non-squamous histology (n=335) adjuvant chemotherapy was associated with an increased risk of BM (HR=2.10, [1.01–4.32], p=0.04) for ERCC1-negative tumours whereas there was no evidence of an effect on brain metastasis for ERCC1-positive tumours (HR=1.07 [0.38–2.99] p=0.90). These 2 effects are nevertheless not different (p for interaction=0.30) possibly by lack of power in this subsample. Conclusions: This study would suggest that cisplatin-based adjuvant chemotherapy is associated with an increased risk of BM in resected NSCLC patients with chemosensitive tumors. This data, if confirmed, could provide a rationale to evaluate prophylactic strategies in this subset of patients. No significant financial relationships to disclose.
Recurrence and survival after pulmonary metastasis in triple-negative breast cancer.
Authors: V. K. Gadiyaram, S. Kurian, J. Abraham, B. Ducatman, H. Hazard, G. Hobbs, L. Vona-Davis
Journal: Journal of Clinical Oncology (2010)

1131 Background: Triple-negative breast cancers are associated with poor outcomes; however, the patterns of metastatic spread following diagnosis are less defined. Methods: Records for 593 patients with breast cancer at West Virginia University Hospital were reviewed (for tumor receptor status and the occurrence of, and time to, first distant metastasis and overall survival) and compared triple-negative versus other receptor subtypes. Distant metastasis-free survival was defined as the interval between the initial diagnosis and the time at which a metastasis to bone and visceral sites (liver, lung, brain) was detected. If more than one site was involved, it was prioritized in the order: liver, lung, brain, and bone. Results: Ninety-five of 593 patients (95/593,16%), developed metastases to bone (40/95) or visceral sites (55/95). Metastases to liver, lung, and brain occurred within the first five years, a latent period that was shorter than that for bone (p= 0.042). The median time to recurrence was shortest in lung, 9.6 months, compared to 25.8 months for brain and 20.9 months for liver (p > 0.024). The probability of developing a visceral metastasis within 5 years was higher among women with triple-negative tumors 21/27(78%) compared to HER2-postive 6/11(55%) and HER2-negative 24/47 (51%) patients. Triple-negative patients with metastasis to lung had a median survival of 18.0 months, followed by brain 26.9, liver 38.2, and bone 50.8 months (p > 0.017) when compared to other breast cancer subtypes. Conclusions: For all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. In this small retrospective study, the overall survival of triple-negative patients with lung and brain was poor compared to liver and bone. Our unique observation of poor survival associated with lung as the initial site of metastasis in patients with triple-negative disease requires further validation. Initial site of metastasis for women with triple-negative breast cancer Median survival, months P value (Wilcoxon test) Bone 50.8 (CI: 38.0-60.6) 0.017 Liver 38.2 (CI: 24.1-40.0) Brain 26.9 (CI: 13.1-27.6)* Lung 18.0 (CI: 5.6-24.4)* No significant financial relationships to disclose.
Antisense oligonucleotides targeting the large subunit (R1) of human ribonucleotide reductase synergistically increase the cytotoxicity of doxorubicin and paclitaxel to MCF-7 breast cancer cells
Authors: X. Jiang, R. L. Elliott, J. F. Head
Journal: Journal of Clinical Oncology (2009)

e14626 Ribonucleotide reductase (RR) is an essential enzyme that catalyzes the reduction of ribonucleotides to deoxyribonucleotides for use in DNA synthesis. Human RR consists of two subunits, a large subunit (R1) and small subunit (R2). RR provides an attractive target for anticancer therapy. In the present study, we synthesized phosphorothioated antisenses oligonucleotides (RR 1 AS 1 , RR 1 AS 2, RR 1 AS 3, RR 1 AS 4 and RR 1 AS 5 ) that target the R1 subunit of RR. We treated the human breast cancer cell line MCF-7 with antisenses, and doxorubicin or paclitaxel for 72 hours. Cell proliferation was measured by 3 [H]- thymidine incorporation. The effects of the drug combinations were analyzed with Biosoft Calcusyn software. The levels of RR mRNA were measured by RT-PCR. We found two antisenses, RR 1 AS 2 and RR 1 AS 4, inhibited the proliferation of MCF-7 cells in a dose-dependent pattern (IC 50 s: 5.32+1.64μm and 2.57+2.72μm, respectively, 72 hours incubation). Also, RR 1 AS 2 and RR 1 AS 4 significantly suppressed the expression of RR 1 mRNA. When MCF-7 cells were incubated in media with a mixture of antisense and doxorubicin or paclitaxel, both RR 1 AS 2 and RR 1 AS 4 synergistically increased the cytotoxicity of doxorubicin and paclitaxel. Calcusyn analysis showed that averaged combination index (CI) were 0.59+0.04, 0.66+0.22, 0.83+0.16 and 0.88+0.03, when MCF-7 cells were treated with the mixtures of RR1AS2 + doxorubicin, RR1AS2 + paclitaxel, RR1AS4 + doxorubicin and RR1AS4 + paclitaxel, respectively (CI&lt;1 indicates synergism). These results suggest that the combination of RR antisenses and chemotherapeutic agents, such as doxorubicin or paclitaxel, may decrease both the dosages and side effects of both antisense oligonucleotides and chemotherapeutic agents (doxorubicin and paclitaxel) in cancer therapy. No significant financial relationships to disclose.
First toxicity and efficacy analysis of a phase II trial of a novel 5-FU-oxaliplatin based chemoradiation schema for stage II and III rectal carcinoma
Authors: E. M. Rishe, S. Malamud, K. Hu, W. Enker, P. Kozuch, R. Blum, J. Martz, M. Bernstein, M. Grossbard, S. Gettinger, I. Shapira
Journal: Journal of Clinical Oncology (2007)

14591 Background: 5-FU based neoadjuvant chemoradiation (CRT) has become the standard of care for stage 2 and 3 rectal cancer (ca). Pathologic complete responses (pCR) and downstaging have been associated with improved survival outcomes. The addition of oxaliplatin or irinotecan to neoadjuvant treatment has led to improved pCR and downstaging. The feasibility and efficacy of “total” oxaliplatin therapy (pre and postoperative oxaliplatin) for stage 2 and 3 rectal ca patients has yet to be defined. Objective: To determine the feasibility, toxicity and efficacy of neoadjuvant oxaliplatin, 5-FU and RT followed by surgery, with postop adjuvant modified FOLFOX6. Methods: Single institution, single arm phase II trial of oxaliplatin 60mg/m 2 weekly for 6 weeks with continuous infusion 5- FU 225 mg/m 2 /excision. Postoperative therapy consisted of mFOLFOX6 every 2 weeks for 6 cycles. Eligibility included previously untreated, histologically proven rectal cancer, T3–4N0M0 or TanyN+M0 (stage II-III). Results: 15 pts have been enrolled in this study. One died of disease prior to CRT. Eight pts have completed total oxaliplatin therapy. One pt had 1 cycle deleted due to grade 2 neuropathy. Prior to adjuvant therapy 2 pts dropped out: 1 from pulmonary symptoms and one asthenia. Two pts attained a pCR and 6 attained downstaging. Significant toxicity has been limited to grade 3 neuropathy in one pt (completely resolved) and one grade 3 GI toxicity (self limited). Conclusions: Early analysis shows the feasibility of pre and post operative oxaliplatin based therapy. The limited data permit only observation of pCR and tumor downstaging rates but toxicity outcomes are encouraging. Further accrual and follow-up will better define efficacy and toxicity of this regimen. [Table: see text]
Results of a phase II trial of a fludarabine with concomitant application of alemtuzumab in a four-weekly schedule (FluCam) in patients with relapsed CLL. 2nd Interim analysis
Authors: T. Elter, P. Borchmann, H. Schulz, M. Reiser, S. Trelle, P. Staib, T. Schinköthe, A. Engert
Journal: Journal of Clinical Oncology (2004)

6693 Background: This phase-II-trial investigated the safety and efficacy of a combined modality treatment with fludarabine (F) and the monoclonal anti-CD52 antibody Alemtuzumab (A) in patients (pts) with relapsed CLL. Objectives of this study were to evaluate the feasibility and overall response rate, to assess the response duration and the residual disease after treatment. Methods: The FluCam schedule consists of an escalation phase of Alemtuzumab up to 30 mg within 3 days and followed by the FluCam combination therapy. F was administered at a dosage of 30 mg/m2/d (day 1–3) immediately followed by the 2h antibody-infusion (30mg; d1–3) and repeated on day 29 for up to 6 cycles. Residual disease was monitored by 4-colour flow cytometry. Results: A total of 28 pts have been recruited so far. Baseline characteristics of these pts are: median age 60.7 years (range 38–80 years); male gender: 23; Binet stage C: 21; median number of prior regimens 2 (range 1–8) including fludarabine in 18 pts, Rituximab in 12 pts and Alemtuzumab in 4 pts. In 28/28 pts Overal Response Rate was 86%. The response rate for the first 14 pts was 7 CR, 5 PR, 1 SD, 1 PD. Assessment of minimal residual disease showed negativity in 8/14 pts in peripheral blood and was confirmed in bone marrow in 4/8 pts. FFTF is 16.5 months with 2 pts in ongoing remission. Therapy was well tolerated with WHO grade 3/4 neutropenia in 10/50 evaluable cycles and severe thrombocytopenia in 11/50 cycles. Conclusion: The second interim analysis of this phase-II study of the FluCam protocol in pts with relapsed CLL suggests that this combination is very effective, feasible and safe. The interim analysis of all 28 pts will be presented. A prospective randomised phase-III-study comparing FluCam with fludarabine is underway. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering AG Medac Schering
Darbepoetin Alfa assessment in chemotherapy induced anemia
Authors: E. Samantas, S. K. Rigatos, A. Konstantinopoulou, G. Vourli, M. Siganaki, D. Pectasides, M. Pectasides, E. Papakostas, G. Karagianidis, G. Aravantinos
Journal: Journal of Clinical Oncology (2006)

18617 Background: Anemia is a very common complication of cancer and its treatment. Epoetins have been proven effective in correcting anemia in cancer patients resulting to the reduction of the need for blood transfusions and having a positive impact to the quality of life (QoL). Darbepoetin alfa, is a novel erythropoiesis stimulating protein (NESP) with longer half life. Methods: This is a prospective, single-centre, clinical trial. Patients with haemoglobin &lt; 12 g/dl, suffering from cancer (solid tumor or lymphoma), for whom chemotherapy is scheduled for at least 12 weeks and have life expectancy &gt;6 months and performance status ECOG 0–2,are treated with Darbepoetin alfa 150 mg per week subcutaneously for at least 12 weeks. Full blood count should be tested at least every 2 weeks and biochemistry every 4 weeks. QoL was assessed before and after treatment using the FACT-An (Functional Assessment of Cancer Therapy-Anemia) scale. Primary endpoint is the correction of anemia (Hb value above 12 g/dl). Frequency of the demographic and clinical characteristics were reported for the categorical variables, while mean and standard deviation were reported for continuous variables, such as age and Hb levels. Results: Fifty-six (56) patients entered the study, 66% of them female. Median age was 64 years. The more common cancers were colorectal (26.8%) ovarian (17.9%), breast (16.1%), lung (12.5%), and bladder (8.9%). Two thirds of the patients had not received previous chemotherapy. A statistically significant increase for Hb was found between week 0 and 12 [1.48; 95% CI 1.07–1.88; p &lt; 0.001]. The increase was significant from 3 rd week onwards. There was no evidence of significant difference in any of the QoL components or for significant change in mean fatigue sub-scale (fatigue, non-fatigue), between the two assessments. Conclusions: Darbepoetin alfa given at 150 mg per week subcutaneously to cancer patients under chemotherapy appears to correct anaemia, but has not positive impact on QoL, within the limits of the sample size of this study. No significant financial relationships to disclose.
Sleep quality, quality of life and their correlative factors in lung cancer patients
Authors: Yanbin Zhou, Yinhuan Li, Wanling Huang, Xingdong Cai, Qingli Zeng, Lixia Huang
Journal: European Respiratory Journal (2011)

Objectives:  To investigate the sleep quality and quality of life in patients with lung cancer.   Methods:  We evaluated the sleep quality and quality of life of 98 lung cancer patients in our hospital by Karnofsky performance status (KPS), the Pittsburgh sleep quality index (PSQI) and the European organization for research and treatment of cancer quality of life questionnaire-core 30 and lung cancer module (EORTC QLQ-C30 and LC13). Then the newly diagnosed patients who had not received any treatment before were reevaluated after a month from the time of diagnosis or the first episode of treatment.   Results:  The respondding rate was 59.8%, and the rate of follow-up in newly-diagnosed patients was 51.5%. Evaluating performance status of lung cancer patients by KPS, 78.6% of them were considered to be able to keep on their normal life or work. The KPS of younger or better educated patients was better than that of older or lower educated ones. Evaluating sleep quality in lung cancer patients by PSQI, 45.9% were classified as poor sleepers. Unmarried patients, patients with college education used sleep medicine more frequently than married patients or patients with primary or high school education. Sleep efficiency was lower in patients with complications than those without complications. Evaluating quality of life in lung cancer patients by EROTC QLQ-C30, Seniles had better emotional and social function and less financial problems than non-senile patients.   Conclusions:  Sleep disturbances did exist in patients with lung cancer, which had a great impact on their quality of life. KPS was still one of the most important factors that influenced quality of life in lung cancer patients.
Implementation of QOPI at Illinois CancerCare, P.C. (ILCC).
Authors: Kendall Howard, Bridgette Heard, Pankaj Kumar, Laura M. Miller
Journal: Journal of Clinical Oncology (2013)

174 Background: ASCO’s Quality Oncology Practice Initiative (QOPI) is a practice based quality improvement program based on retrospective chart reviews. Data collection is performed twice a year. If scores meet a specified level, a practice may apply for certification. In order to achieve certification, a physician practice must meet minimum threshold scores in five areas including: Core, Symptom/Toxicity, Care at End of Life, Breast Cancer, Colon/Rectal Cancer and Non-Small Cell Lung Cancer. A QOPI on-site review is conducted after application. Once the application has been approved, the on-site review includes an audit of chemotherapy preparation and administration, patient education, treatment planning and the review of applicable policies. If acceptable, a 3 year certification is awarded to the practice. Methods: ILCC began QOPI participation in Fall 2011. For the first round, the scores were lower than the required minimum threshold certification score level requirements. The certification areas with lower than desirable scores included: Pain Score Assessed, Emotional Well Being Assessed and Colonoscopy within specified time frame. To improve scores, a committee was formed to identify improvements. Improvements included revising physician templates to include new areas and language. Physicians were also given the appropriate verbiage for assessing a patient’s Emotional Well Being, and employees also were engaged in our improvement efforts by addressing areas that needed to be asked in the first and second visits only. Results: All selected measures show improvement from Fall of 2011 to Spring of 2013. Pain addressed appropriately increased 59% (26% to 80%); patient emotional well being assessed increased 32% (19% to 51%), colonoscopy before or within 6 months of curative colorectal resection improved 35% (50%-86%). Our total certification score went from 72.05% to 87.99%, a 15% improvement. We applied for certification and became a QOPI certified practice in fall of 2012. Conclusions: QOPI is an effective program for evidence based quality improvement within oncology practices.