tbuckley/cabot-search huggingface dataset:
Results of pooled analyses from two phase III trials of 1,085 patients (pts) with advanced melanoma: Oblimersen (OBL) plus dacarbazine (DTIC) versus DTIC alone.
Authors: A. Y. Bedikian, C. Lebbé, C. Robert, S. S. Agarwala, J. Wu, C. Garbe, J. J. Grob
Journal: Journal of Clinical Oncology (2010)

8573 Background: We conducted two phase III trials (GM301 and AGENDA) of DTIC ± OBL in pts with advanced melanoma. Overall survival (OS) was a primary or co-primary endpoint in both studies. The AGENDA analysis plan prospectively specified a “pooled analysis” of OS in both studies. As AGENDA data on OS and durable response are still being collected, we conducted exploratory analyses of early OBL effects using data available from both trials. Methods: A total of 771 and 314 chemotherapy-naïve pts were randomized in GM301 and AGENDA, respectively. Entry criteria were similar in both studies. AGENDA was a double-blind study limited to pts with low-normal baseline LDH levels (≤ 0.8 × ULN), whereas GM301 was open-label and had no LDH restriction. All pts received DTIC ± OBL every 3 weeks. Data from AGENDA were pooled with data of (1) the ITT group in GM301 and (2) the 274 pts with low-normal baseline LDH in GM301 and compared by treatment. PFS was assessed by the log-rank test; ORR was assessed by the Cochran-Mantel-Haenszel test. Results: In DTIC-OBL-treated pts, the ITT ORR in GM301 and AGENDA was 13.5% and 17.2%, respectively, and 20.8% in the GM301 low-normal LDH group. In DTIC-treated pts, the ITT ORR in GM301 and AGENDA was 7.5% and 12.1%, respectively, and 7.2% in the GM301 low-normal LDH group. Response data combined from both trials show an ITT ORR of 14.5% in DTIC-OBL pts vs. 8.9% for DTIC pts (p = 0.004) and a low-normal LDH ORR of 19.0% vs. 9.9% (p = 0.002), respectively. PFS hazard ratio for the ITT group in GM301 and AGENDA was 0.75 and 0.85, respectively, and for the GM301 low-normal LDH group, 0.58. In DTIC-OBL-treated pts, PFS data combined from both trials show a median increase in PFS of 1 month in ITT pts (HR = 0.78; p = 0.0004) and of 1 month in the low-normal LDH group (HR = 0.71; p = 0.0004). Conclusions: Pooled analysis confirms OBL + DTIC is associated with an increase in ORR and modest improvement in PFS, compared with DTIC alone. In the ITT analysis, absolute and proportional improvement in ORR is 5%-6% and 42%-80%, respectively. As ORR and PFS are not established as clinical benefit endpoints in this population, pt follow-up for OS and durable response is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genta Abraxis BioScience, Bristol-Myers Squibb, Genta, ImClone Systems, Novartis Genta Genta, ImClone Systems Genta Genta
The effect of chemotherapy on cognitive and cerebellar function in patients with acute myeloid leukemia
Authors: D. E. Kuczynski, M. Minden, S. M. H. Alibhai
Journal: Journal of Clinical Oncology (2005)

6692 Background: Standard treatment of patients with Acute Myeloid Leukemia (AML) includes cytarabine (Ara-C). Some patients receiving Ara-C have described confusion, incoordination and poor balance, suggesting possible cerebellar and/or cognitive dysfunction. However, there are no published data investigating this phenomenon. We therefore evaluated performance on fine motor tasks and other areas of cognition. Methods: Patients with AML receiving Ara-C either during induction (200 mg/m2/day for 7 days) or first consolidation (3 g/m2 every 12 hours on days 1, 3, and 5) were eligible. Induction patients underwent computer-based testing on days 1, 14, and 28 of their cycles. Consolidation patients underwent testing on days 1, 3, 5, 8, 14, and 28. The computer tests used were the Amsterdam Neuropsychological Tasks (ANT), testing fine motor skills, and 5 of 6 tasks from the IMPACT concussion management test, examining verbal, visual and spatial memory. Results: Eight patients (5 induction, 3 consolidation; mean age 43, range 20–73) were enrolled in July and August 2004. Of the three cerebellar tasks (tracking, tapping, and pursuit), the induction group showed evidence of mild decline by day 28 in the tapping task and, to a lesser extent, in the tracking task. Changes were more noticeable in the non-dominant hand. The pursuit task did not show any worsening over time. Memory-based tasks either showed no change or mild improvement, likely due to practice effects. Although consolidation patients could not be compared directly to induction patients, they did not demonstrate worse function at baseline and did not deteriorate on either cerebellar or memory-based tasks over the 4-week period. Conclusions: Ara-C may be associated with adverse cerebellar effects, particularly in repetitive fine motor tasks. Cerebellar dysfunction may preferentially affect the non-dominant side. Further studies with larger patient samples are warranted. No significant financial relationships to disclose.
Phase Ib study of the anti-neovascular agent MBT-0206 to evaluate safety and efficacy in patients with metastatic breast cancer
Authors: K. Bartelheim, N. A. Ognerubov, V. F. Semiglazov, O. M. Vtoraya, C. Kaletta, I. Reichenberger, U. Michaelis, K. Naujoks, M. Clemens
Journal: Journal of Clinical Oncology (2004)

3079 Background: MBT-0206 is a highly innovative anti-neovascular cytostatic compound designed to target and destroy newly formed tumor blood vessels. Its superior anti-tumor activity based on this new concept has been shown in several animal models. In addition MBT-0206 (lipid-complexed paclitaxel) was shown to be effective in paclitaxel-resistant tumors. This phase Ib clinical study was conducted to evaluate safety and anti-tumor efficacy of MBT-0206 in patients with metastatic breast cancer and tumor progression after anthracycline based chemotherapy. Methods:MBT-0206 was administered as intravenous short infusion in two different dosages to 18 patients each group. Dose group A: 0.55 mg/kg body weight lipid-complexed paclitaxel and dose group B: 1.1mg/kg on day 1, 3, 5 of a 3 week cycle. Safety was assessed on the basis of reported adverse events and efficacy was measured as objective tumor response according to RECIST criteria. Results: The main toxicities in group A were vomiting 28%, nausea 22% anemia 17% and infusion related reactions 56% and in dose group B: thrombocytopenia 44%, neutropenia 33%, asthenia 22% and infusion related events 28%. No neuropathy and only 11% of alopecia have been observed. The overall assessment of tumor response showed 6% PR and 28 % SD in dose group A and 56% SD in dose group B. Four patients continued treatment in an amendment. After in total 6 treatment cycles 2 patients showed SD and 1 patient PR. No cumulative toxicities have been observed. Conclusions: The favourable safety profile together with promising efficacy data of MBT-0206 evaluated in phase Ib studies justify subsequent phase II studies. Good tolerability as well as the different mechanism of action of MBT-0206 offer the possibility of prolonged treatment or combination therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Munich Biotech AG Munich Biotech AG
Quality measures for the diagnosis and management of colorectal cancer
Authors: M. B. Patwardhan, G. P. Samsa, M. A. Michael, R. G. Prosnitz, D. A. Fisher, C. R. Mantyh, D. C. McCrory
Journal: Journal of Clinical Oncology (2006)

16031 Background: The huge burden of illness from colorectal cancer (CRC) can be reduced by improving the quality of care for CRC patients. Identifying appropriate quality measures that can assess the processes of care is the first step in this process. Therefore we conducted a comprehensive literature search to identify process measures available in the United States to assess the quality of care for diagnosing and managing patients with CRC and the extent to which they were field-ready. Methods: We conducted a standard literature search using MEDLINE and the Cochrane Database; also explored gray literature, and identified 3771 abstracts. By sequential exclusion, 74 of them were finally included. We included quality measures from traditional QI literature, and supplemented them with those included in studies where these measures were used as part of their research agenda. All measures were abstracted into evidence tables and evaluated using a set of standard criteria regarding their importance, usability, and scientific acceptability. In order to assess the extent to which they were field-ready, we devised a summary rating scale for each quality measure using three criteria: importance and usability, scientific acceptability, and extent of testing. Results: Overall, the coverage of general process measures in CRC is extensive. Process measures are available for diagnostic imaging, staging, surgical therapy, adjuvant chemotherapy, adjuvant radiation therapy, and colonoscopic surveillance. The highest rated measures were those related to chemotherapy (abstract submitted by Morse et al) and pathology reporting. There were no process measures for assessing the quality of: polyp removal, surgical management of stage IV rectal cancer, hepatic metastasis, chemotherapy for stage II colon cancer, stage IV rectal cancer, radiation for stage IV rectal cancer, and notes for endoscopy, surgery, chemotherapy and radiology - all because of lack of guidelines. Conclusions: Our evidence report suggests that we need to actively pursue the task of developing scientifically accurate quality measures for leverage points in the diagnosis and management of CRC; so we can evaluate the quality of care delivered by providers and initiate quality improvement activities, with the aim of providing better patient care. No significant financial relationships to disclose.
Multidisciplinary system for detecting medication errors in antineoplastic chemotherapy
Authors: D. Almenar-Cubells, V. Jimenez Torres, A. Serrano Fabia, A. Albert Mari, C. Molins Palau, C. Bosch Roig, S. Olmos Anton, V. Jimenez Arenas, J. Muñoz Langa, R. Llorente Domenech
Journal: Journal of Clinical Oncology (2006)

6136 Background: The aim of this study is to quantify medication errors (ME) in a multidisciplinary system with a Computerized Pharmacotherapy Process (CPP) in cancer patients. Methods: Longitudinal, prospective, and cohorts study during 2 years (January, 2003-December, 2004) in adult patients who received antineoplastic treatment in Oncology and Haematology services. ME were identified by double cross-validation of every stage of the pharmacotherapy process (prescription, preparation, dispensation, administration and follow-up) carried out by the multidisciplinary team (physician, pharmacist, nurse) with CPP assistance. Variables: number of ME for 1000 patients-day, % according to the stage of the process and severity (scale to 1 -not damage in the patient- to 5 -irreversible damage-) of ME intercepted. Results: 638 patients were on treatment and ME were identified in 225 (35%). On a total of 18,785 preparations and 13,206 patients-day, 276 ME were detected, equivalent to 20.9 ME by 1000 patients-day (95%CI: 18.5–23.5); of these 16.8 ME for 1000 patients-day (80.1%) were intercepted and did not reach a patient (95%CI: 14.6–19.1). ME detected distribution according to the stage were: prescription 75.7% (95%CI: 70.2–80.7), preparation 21.0% (95%CI: 16.4–26.3), dispensation 1.8% (95%CI: 0.6–4.2), administration 1.1% (95%CI: 0.2–3.1), and follow-up 0.4% (95%CI: 0.01–2.0). ME distribution according to the severity were: grade 1: 15.9% (95%CI: 11.8–20.8), grade 2: 49.6% (95%CI: 43.6–55.7), grade 3: 33.7% (95%CI: 28.1–39.6), grade 4: 0.7% (95%CI: 0.1–1.6) and none of grade 5. The system intercepted 98.9% (95%CI: 94.3–99.9) of ME with severity equal or greater than 3 -ME with potential to damage the patient- and 70.2% (95%CI: 62.9–76.7) of severity equal or minor to 2, ME without clinical significance. Conclusions: The multidisciplinary system with well-established CPP detects 20.9 ME for 1,000 patients-day and intercepts 98.8% of ME with potential to damage the oncology patient. No significant financial relationships to disclose.
Tissue levels of cisplatin in previously traumatized tissue without adhesion formation in a rabbit sidewall adhesion and intraperitoneal delivery model
Authors: C. S. Awtrey, K. E. Greenawalt, J. M. Colt, R. L. Corazzini, M. Philbrook, M. R. Santos, R. E. Bristow
Journal: Journal of Clinical Oncology (2009)

5525 Background: It has been hypothesized that the presence of extensive adhesions after ovarian cancer resection may limit the distribution of intraperitoneal (IP) chemotherapeutics. The objective of this study was to determine if using a hyaluronate/carboxymethylcellulose (HA/CMC) barrier to prevent adhesions during a simulated tumor resection surgery would increase tissue drug levels following subsequent IP chemotherapy. Methods: A sidewall defect/cecal abrasion model was used to induce adhesion formation and simulate tumor resection trauma in 22 rabbits. Seven rabbits received HA/CMC at the end of the surgery. Four weeks after surgery, cisplatin (2.5mg/kg) was administered IP to HA/CMC treated and untreated animals or IV to untreated controls. Animals were sacrificed 24hrs after infusion and tissue samples were collected from inside the defect (with or without adhesions) and outside the defect on the contralateral sidewall. Samples were cryosectioned and analyzed for platinum content by ICP/MS. Results: Platinum tissue levels in the uppermost peritoneal layer (0–1mm) were significantly higher for IP delivery than IV and were the highest for IP delivery when no adhesions were present inside the defect. Platinum levels were significantly higher in the previously traumatized tissue inside the defect than in untraumatized tissue outside the defect. This was consistent for both IP or IV and HA/CMC treated or untreated animals. The benefit of HA/CMC was underscored by the fact that samples under adhesions could not be obtained for that group due to the significant reduction in adhesion formation compared to untreated controls. Conclusions: Recently traumatized tissue without adhesions had the highest platinum levels following IP cisplatin in this model. The previously traumatized tissue had significantly higher platinum levels than untraumatized tissue likely due to both increased peritoneal diffusion and systemic delivery components. [Table: see text] [Table: see text]
Changes in FDG-PET in response to rapamycin (R) correlated with Akt pathway inhibition and not with clinical outcome
Authors: W. Ma, D. Song, H. Jacene, F. Vilardell, X. Zhang, W. Messersmith, C. Endres, A. Jimeno, M. Pomper, M. Hidalgo
Journal: Journal of Clinical Oncology (2008)

3511 Background. FDG-PET is increasingly been used to measure antitumor effects in clinical trials with novel agents. Here we investigated the role of FDG-PET in predicting response to R in refractory solid tumor (RST) patients (pts) and the basis for the observed results in a preclinical cancer model (PCM). Methods. RST pts were treated with R (2 to 9 mg daily) in a phase I trial. FDG-PET/CTs were done at baseline and after 8 weeks of R. Five areas with the highest FDG uptake at baseline (SUVmax) were selected as target lesions. Percent change in mean SUVmax between baseline and after 8 weeks of R were compared for each patient, categorized by EORTC (1999) PET response criteria and correlated with tumor response by RECIST criteria. Tumors from 4 pts with pancreatic cancer were xenografted onto nude mice, expanded and treated with the R analog temsirolimus (TEM). Preclinical FDG-PET scans were obtained on day 0 and after 1 week of TEM. Drug efficacy was determined on day 28 by the T/C ratio. Changes in the Akt activation and glycolytic pathway were studied by Western Blot and immunohistochemistry. Results. Serial FDG-PETs were evaluated in 19 pts with gastrointestinal, uterine, and neuroendocrine carcinomas and sarcomas. Ten (53%) had partial metabolic response (PMR) and 9 (47%) had stable metabolic response (SMR). There was no relationship between R dose and FDG-PET response. In the PMRs, 5 had progressive disease (PD) and 5 had stable disease (SD). In the SMRs, 4 had PD and 5 had SD. Puzzled by the disconnection between FDG-PET and objective response, we studied TEM’s effects in a PCM. In the 4 TEM-resistant (T:C ratio ≥ 50%) xenograft models, 2 had stable/increased SUVmax (PET-R) and 2 had reduced SUVmax (PET-S) from baseline, similar to the clinical observation. Biomarkers studied indicated suppressed Akt and glycolitic pathway in the TEM-treated PET-Ss but persistence in the PET-Rs. Conclusions. FDG-PET response does not predict tumor proliferative response to mTOR inhibitor therapy in ST pts. PCMs suggest that FDG-PET is a pharmacodynamic marker for Akt activity in this setting. We hypothesized that, in a subset of tumors, R suppresses TORC2 complex resulting in inhibition of Akt and glycolysis, thus FDG-PET response, but this is independent of the effects on tumor proliferation. No significant financial relationships to disclose.
Palliative effect of metaiodobenzylguanidine in metastatic carcinoid tumors.
Authors: B G Taal, C A Hoefnagel, R A Valdes Olmos, H Boot, J H Beijnen
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate the therapeutic effect of iodine-131-labeled metaiodobenzylguanidine (131I-MIBG) and unlabeled MIBG in patients with carcinoid tumor. MATERIALS AND METHODS A therapeutic dose of 7.4 GBq (200 mCi) 131I-MIBG infused over 4 hours was administered to 30 patients with either carcinoid syndrome (n = 20) or tumor symptoms such as pain and fever due to carcinoid tumor (n = 10). In general, two courses were given, 6 weeks apart. Due to radioactivity, patients had to be isolated for 5 to 7 days. Subsequently, we studied the effect of unlabeled MIBG based on the possible pharmaceutic activity of MIBG and to avoid the isolation procedure. A doseescalation study of 8.5, 17, and 34 mg/m2 MIBG infused over 4 hours at 4-week intervals was performed in 20 patients with carcinoid syndrome who were not suitable for treatment with the radioactive compound. RESULTS Following 131I-MIBG treatment, symptomatic responses were observed in 60% of patients (median duration, 8 months; maximum, 2 years). Side effects were mild and rapidly reversible in 16 patients, and were related to the isolation procedure in seven of these patients. Unlabeled MIBG resulted in symptomatic improvement in 60% of patients (median duration, 4.5 months). Side effects, which included changes in blood pressure, were mild and transient. Symptomatic responses were not accompanied by biochemical responses. CONCLUSION Both MIBG treatment regimens were equally effective in the palliation of symptoms, but duration of response tended to be much longer with the radioactive compound. However, the unlabeled compound provided a simpler treatment, eg, in elderly patients and those in poor condition, without the need for isolation.
Radiation with cisplatin or carboplatin for locally advanced cervix cancer: The experience of a tertiary cancer center.
Authors: George Au-Yeung, Linda R. Mileshkin, David Bernshaw, Srinivas Kondalsamy-Chennakesavan, Danny Rischin, Kailash Narayan
Journal: Journal of Clinical Oncology (2012)

e15541 Background: Definitive treatment with concurrent cisplatin and radiation is the standard of care for locally advanced cervical cancer. The optimal management of patients with a contraindication to cisplatin has not been established. We conducted a retrospective audit of the impact of concurrent chemoradiation in a cohort of patients (pts) with locally advanced cervical cancer. Methods: All pts with locally advanced cervical cancer treated with definitive radiation were entered into a prospective database. Information regarding their demographics, stage, histology, recurrence and survival were recorded. Pharmacy records were reviewed to determine concurrent chemotherapy use. The primary endpoint was overall survival, and secondary endpoints were disease free survival and rates of primary, nodal or distant failure. Univariate and multivariate analyses were performed, incorporating known prognostic factors of age, FIGO stage, uterine body involvement, tumour volume on MRI and nodal involvement. Results: 442 pts were treated from Jan 1996 to Feb 2011. Median age was 59 (range 22-94); 89% had squamous histology and 64% node-negative disease. 269 pts received cisplatin, 59 received carboplatin because of a contraindication to cisplatin and 114 received no concurrent chemotherapy (most prior to 1999). Overall survival adjusted for other prognostic factors was significantly improved with use of concurrent cisplatin compared to radiation alone (HR 0.53, p=0.001), as was disease free survival and the rate of distant failure. Use of concurrent carboplatin was not associated with any significant benefit compared to radiation alone in terms of overall survival or disease free survival on univariate or multivariate analyses. Conclusions: The results of this audit are consistent with the known significant survival benefit with concurrent cisplatin chemoradiation. However, there did not appear to be any significant benefit associated with concurrent carboplatin although there are potential confounding factors in this small cohort. The available evidence in the literature favors the use of non-platinum chemotherapy rather than carboplatin in pts with contraindications to cisplatin.
Models predictive for survival in untreated patients with CLL at initial presentation and initial treatment
Authors: W. G. Wierda, S. M. O’Brien, X. Wang, A. Ferrajoli, S. H. Faderl, F. Ravandi-Kashani, K.-A. Do, H. Kantarjian, S. Lerner, M. J. Keating
Journal: Journal of Clinical Oncology (2005)

6593 Clinical characteristics of patients with chronic lymphocytic leukemia (CLL) have been correlated with meaningful clinical endpoints such as time-to-treatment, response, progression-free survival (PFS) and overall survival (OS). Identification of such characteristics enables informed discussion about treatment options, planning, and can provide insight into basic biology of CLL. Rai and Binet staging incorporate physical and laboratory data including presence of adenopathy, organomegaly, anemia, and thrombocytopenia. To increase the power of current staging, we identified 1607 previously untreated patients with CLL at initial presentation to MDACC for analyses. Based on significant characteristics identified in univariate analyses, a multivariate model was developed for OS. Characteristics evaluated included age, gender, Rai and Binet stage, performance status (PS), # of affected node sites, WBC count, absolute lymphocyte count (ALC), HGB, PLT, ALB, serum alkaline phosphatase (AP), % BM lymphocytes, spleen and liver size, and beta-2 microglobulin (β2M). In addition to age and stage, multiple characteristics significantly correlated with OS. A multivariate Cox proportional hazards regression model was developed that identified the following combination of covariates associated with OS: age (p<0.0001), Rai stage (p=0.0002), ≥3 affected node sites (p=0.007), ALC (p=0.001), β2M (p<0.0001), and AP (p=0.001). A nomogram was developed using these characteristics to predict OS in untreated patients initially presenting to MDACC. A 561 patient subgroup went on initial therapy upon presentation to MDACC and was analyzed for predictors of OS. In addition to age and Rai stage, multiple characteristics were significantly correlated with survival. The multivariate Cox proportional hazards regression model included the following combination of covariates as significant predictors of OS: age (p<0.0001), AP (p=0.005), β2M (p=0.05), and PS (p=0.05). Nomograms have been developed for both PFS and OS in this population. These nomograms are powerful tools for predicting important clinical endpoints including survival, for counseling patients, and developing and analyzing clinical trials. No significant financial relationships to disclose.