tbuckley/cabot-search huggingface dataset:
Phase II study of erlotinib given daily for patients with metastatic melanoma (MM)
Authors: K. Wyman, M. Kelley, I. Puzanov, K. Sanders, F. Hubbard, P. Krozely, D. Sturgeon, V. Viar, J. A. Sosman
Journal: Journal of Clinical Oncology (2006)

18002 Background: Erlotinib is a small molecule tyrosine kinase inhibitor (TKI) that targets epidermal growth factor receptor (EGFr). The EGFr is a potential therapeutic target because it is expressed by a number of malignancies, including melanocytic lesions, and in some plays an important role in the biology of the cancer. Our aim was to conduct a phase II study evaluating erlotinib in patients (pts) with measurable metastatic melanoma. Methods: Eligibility criteria included measurable disease, ECOG PS = 0–1, and adequate organ function. Pts were eligible if they received up to one prior therapy for metastatic disease. Pts received a daily dose of erlotinib 150 mg. The primary outcomes were overall response rate and response duration. The study had a two-stage design with closure at 14 pts if there were no objective RECIST responses. Secondary outcomes included overall safety and tolerability of erlotinib. Results: Between August 2003 and August 2004, a total of 14 pts with MM were accrued. The majority of pts were male 12:2 = M, median age = 57.5 yrs (range 38 to 80 yrs). Stage of disease included M1a (n = 7), M1b (n = 5), M1c (n = 2) and performance status was equally divided between 0 and 1 (7 pts each). Seven pts (50%) had prior adjuvant therapy and six pts (43%) had at least one prior therapy for metastatic disease. Four pts (29%) had no prior therapy. No objective responses were observed. Four pts (29%) had stable disease at their initial 8-week evaluation of which only 2 had SD&gt;6 months (228 and 365 days). One pt with SD withdrew from the study on day 68 for grade II toxicities. There were no Grade III/IV hematological or biochemical toxicities. Grade III toxicities were diarrhea and anorexia, each in a single patient. Most pts (n = 12) experienced at least a grade I dermatological toxicity manifested as an acneiform rash and/or pruritis. The median progression free survival (PFS) of all 14 pts was approximately 60 days with a range of 35 to 365 days. The median PFS of those with SD was 192.5 days. Conclusions: Erlotinib given daily at 150 mg is well tolerated in pts with MM. However, it has minimal to no single agent activity. Any further investigation of this drug should be pursued in combination with other agents only if a strong scientific/clinical rationale exists. No significant financial relationships to disclose.
Long-term results after consolidation radiotherapy on residual disease < 1 cm in 106 stage III ovarian cancer patients
Authors: T. Petit, M. Velten, A. Dhombres, C. Marchal, P. Quetin, J.-P. Gérard, F. Mornex, P. Romestaing, S. Schraub, C. Carrie
Journal: Journal of Clinical Oncology (2004)

5039 Background: Attempts to increase survival of stage III ovarian cancer patients (pts), with macroscopic complete response at second-look laparotomy, have included prolonged chemotherapy, dose intensification, and consolidation radiotherapy. We present long term survival of 106 pts treated between 1983 and 1993 for stage III ovarian adenocarcinoma with first-look debulking, cisplatin-based chemotherapy, second-look surgery with a residual disease < 1 cm and consolidation radiotherapy. Method: Median age was 52 years (range 16–73). Residual disease after first look surgery was < 1 cm for 40,5 % of pts. Residual disease < 1 cm was obtained in all pts after second look surgery, with 33% of pts without residual disease. Radiation was performed using a linear accelerator. The whole abdomen dose was 22 Gy with antero-posterior fields and a maximal kidney dose of 20 Gy. 71 pts received a 25 Gy pelvic boost. 33 patients received an additional 12 Gy lombo-aortic boost. Results: Median follow-up was 14 years. Radiation was stopped for acute toxicity in 11 pts. Long term toxicities included radiation enteritis in 21 pts with 9 pts requiring surgery for bowel obstruction, radiation cystitis in 4 pts, acute leukemia in 2 pts, dysmyelopoiesis in 1 pt, skin cancers in the radiation field in 1 pt, bilateral femoral head necrosis in 1 pt. 4 pts died because of radiation complications. Second cancer was diagnosed in 12 pts with 7 breast adenocarcinomas, 3 colon adenocarcinoma, 1 non-small cell lung cancer, and 1 pancreatic cancer. Overall survival (OS) at 5 and 10 years was respectively 53% and 36 %. The main prognostic factor was residual disease after initial surgery, with a 10-year survival of 54 % with no or microscopic residual disease, 48 % with < 1 cm residual disease, 25 % with 1–2 cm residual disease. Conclusion: Long term survival of our patients compares favorably to those of similar patients treated in phase II studies with consolidation high-dose chemotherapy (5 year survival < 40%), at the price of high toxicity incidence (3,7 % of toxic deaths). No significant financial relationships to disclose.
Japanese prostate cancer outcome study of permanent I-125 seed implantation (J-POPS study): Interim results of a prospective cohort study assessing efficacy, safety and QOL
Authors: S. Saito, T. Kiba, M. Aoki, K. Ito, H. Koga, T. Yamashita, S. Kitagawa, T. Daimon, T. Dokiya, H. Yamanaka
Journal: Journal of Clinical Oncology (2008)

16137 Background: Brachytherapy with permanent iodine-125 (I-125) seed implantation has been approved in Japan in July 2003. Multi-institutional cohort study (J-POPS study) assessing the treatment feature, efficacy, safety and health related quality of life (QOL) has begun in July 2005. Over 2,700 patients from 49 institutes are enrolled in this study until the end of October 2007 and finally 8,000 patients in total is expected to be enrolled until the end of 2010. The interim results of this ongoing study have been evaluated. Methods: Forty-three institutions combined data on 1,217 cases treated between July 2005 and February 2007 are analyzed for this interim study. Patient’s background, cancer character, treatment feature such as combined therapy of external beam or hormone, post implantation dosimetric information, treatment efficacy with PSA level, voiding symptoms with IPSS and treatment related adverse events according to NCI- CTCAE are characterized. PSA was measured every 3 months and symptoms accompanied to the treatment were assessed 3 and 12 months after the treatment. The primary end point of the study is biochemical or clinical failure. Results: Average age was 67.8 and 99.2% of the cases were performance status (PS) 0. PSA level on cancer diagnosis was 2.48 to 260 (mean 7.04) ng/ml, clinical stage T2a or less was in 89.56%, T2b-T2c in 9.78%, and T3a-T3b in 0.66%. Gleason score less than 7 was in 52.5%, 7 in 43.3%, and above 7 in 4.2%. Preoperative hormone therapy was performed in 53.16% and external beam (total dose of 45 Gy) was combined in 28.4%. CT based first post therapeutic month dosimetry revealed that prostatic mean V100 and D90 for the cases treated with seed alone were 94.7% and 161.2 Gy, respectively. As for adequate control of radiation dose at rectum (mean R100 = 0.28 cc) and urethra (mean D5 = 220 Gy), toxicities at 3 month over grade 3 was 0%, and grade 3 toxicity was seen only in miction pain (0.26%), pollakisuria or urgency (0.38%), and dysuria (0.38%). Only toxicity over grade 2 seen at 12 month was dysuria (2.14%). Conclusions: Nationwide cohort study for prostate brachytherapy has been executed in Japan to clarify the racially original evidence of the treatment. No significant financial relationships to disclose.
Pharmacogenetic analysis of paclitaxel in breast cancer
Authors: S. Marsh, G. Somlo, H. L. McLeod, X. Li, P. Frankel, C. R. King, W. D. Shannon, T. W. Synold
Journal: Journal of Clinical Oncology (2005)

3058 Background: Paclitaxel is one of the most active single agents in the treatment of breast cancer and is an important component of many commonly used combination regimens. Despite its clinical activity, variability in toxicity and response remain a major problem for patients receiving paclitaxel. Significant variability (4–10 fold) in paclitaxel clearance may contribute to the unpredictability of clinical outcomes. Methods: To determine the contribution of inherited differences in drug metabolism and excretion to the pharmacokinetics and progression-free survival in patients receiving paclitaxel, genomic DNA was isolated from the plasma of 93 patients with high-risk primary (84% stage II with ≥ 10 axillary nodes, stage IIIA or stage IIIB inflammatory carcinoma) or stage IV (16%) breast cancer. Patients received paclitaxel 575–775 mg/m2 infused over 24 hours, doxorubicin 165 mg/m2 as a continuous infusion over 96 hours, and cyclophosphamide 100 mg/kg. Median overall follow-up was 52 months. Ten polymorphisms in 6 genes associated with metabolism (CYP2C8, CYP1B1, CYP3A4 and CYP3A5) and transport (ABCB1 and ABCG2) of paclitaxel were analyzed using Pyrosequencing. Results: In a preliminary analysis of genotype versus phenotype, we found no association between ABCB1, ABCG2, CYP1B1, CYP3A4, CYP3A5 and CYP2C8 genotypes and paclitaxel clearance. However, the CYP1B1*3 (4326 C>G; L432V) allele was associated with survival. Patients homozygous for the Leucine allele (45% frequency) had a significantly longer progression free survival (median: 56 months) than patients with at least one Valine allele (median: 30 months; p = 0.037). This association was independent of stage or estrogen/progesterone receptor status. Conclusions: The CYP1B1*3 allele was significantly associated with progression free survival in patients receiving paclitaxel. This finding could reflect altered paclitaxel metabolism. Alternatively, the role of CYP1B1 in estrogen metabolism may influence the risk of invasive or paclitaxel resistant breast cancer in patients carrying the CYP1B1*3 allele. Additional loci and phenotypes are currently being investigated to determine the role of pharmacogenetics on outcome in breast cancer. Supported by CA 33572, CA 62505 and U01 GM63340. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Neopharm, Orion Genomics, Sanofi-Synthelabo, Veridex Merck Bristol
Extended safety and efficacy data on S-1 plus cisplatin in patients with advanced gastric carcinoma in a multi-center phase II study
Authors: H. Lenz, F. C. Lee, D. G. Haller, D. Singh, A. B. Benson, D. Strumberg, R. H. Yanagihara, J. C. Yao, A. T. Phan, J. A. Ajani
Journal: Journal of Clinical Oncology (2006)

4083 Background: We obtained additional phase II safety and efficacy data in a multi-center setting on an active regimen of S-1 plus cisplatin; the experimental arm of the global phase III First-Line Advanced Gastric cancer Study (FLAGS). Methods: Eligible patients had untreated advanced gastric cancer (AGC), histologic proof, KPS ≥70%, adequate organ function, and gave written consent. Patients received S-1 (25mg/m 2 p.o. bid on days 1–21) plus cisplatin (75mg/m 2 i.v. on day 1) every 28 days. All reported confirmed overall response rate (C-ORR), response durations, and time-to-progression (TTP) are externally reviewed. Results: All 72 patients were assessed for safety and 64 for efficacy. The median age was 56 years and median KPS was 90%. Median no. of cycles was 4. C-ORR was 50% (95% CI, 37%-63%). Median duration of response is &gt;6 months. At 6 months, only 35% of patients have had cancer progression. Median survival (n=72) is 10.5 months (95% CI, 9.3 to NR). At least one SAE occurred in 43% of patients. The frequent grade 3 or 4 adverse events (occurring in &gt;10% of patients) included: fatigue/asthenia (26%), vomiting (21%), nausea (18%), diarrhea (17%), neutropenia (18%), anorexia (11%), and dehydration (11%). Febrile neutropenia (1.4%) and grade 4 diarrhea (1.4%) were rare. Conclusions: These extended data confirm that S-1 plus cisplatin has a very desirable safety profile and impressive efficacy data in AGC. FLAGS will complete accrual of &gt;700 patients by March of 2007. (Supported by Taiho Pharma-USA). [Table: see text]
Randomized phase II study of cetuximab in combination with cisplatin (C) and vinorelbine (V) vs. CV alone in the first-line treatment of patients (pts) with epidermal growth factor receptor (EGFR)-expressing advanced non-small-cell lung cancer (NSCLC)
Authors: R. Rosell, C. Daniel, R. Ramlau, A. Szczesna, M. Constenla, B. Mennecier, W. Pfeifer, M. Mueser, I. Montaner, U. Gatzemeier
Journal: Journal of Clinical Oncology (2004)

7012 Background: NSCLC is a tumor with high EGFR-expression in the majority of cases. Since there is still a need for improvement in the outcome of patients with NSCLC, we evaluated the addition of cetuximab (Erbitux), an IgG1 monoclonal antibody targeting the EGFR, to CV, a standard chemotherapy in NSCLC, in first-line treatment of patients with NSCLC. Combinations of cetuximab and chemotherapy have shown to be effective and safe in several EGFR-expressing tumors such as colorectal cancer and head and neck cancer. Methods: Neither of the patients had received prior chemotherapy. All patients were treated with C 80 mg/m2 d1 and V 25 mg/m2 d1 and 8, q3 and were randomized to either receive additional cetuximab 400 mg/m2 week 1 and 250 mg/m2 weekly thereafter (arm A) or no additional treatment (arm B). Results: 101/112 (90%) of pts screened had EGFR-expressing tumors. Enrollment was completed with a total of 86 pts: 43 (10 f, 33 m) in arm A and 43 (12 f, 31 m) in arm B. The following patient/tumor characteristics were similar in both treatment arms: median age of 58 y (34–75), median KPS of 90, 92% of patients had stage IV NSCLC, 42% had adenocarcinoma and 42% had squamous cell carcinoma. Relevant grade 3/4 adverse events in arm A (B) were: leucopenia 64.3% (51.2), nausea/vomiting 16.7% (14.0), asthenia/fatigue 16.7% (2.3), infection 11.9% (4.7), fever/chills 9.5% (7.0), thrombocytopenia 7.1% (4.7), acne-like rash 4.8% (0), diarrhea 2.4% (0). Confirmed response rates based on preliminary assesment of 41 pts in arm A were 31.7% (C.I.: 17.5 - 46.0) [13 PR, 18 SD, 3 PD], and of 40 pts in arm B: 20.0% (C.I.: 7.6 –32.4) [8 PR, 17 SD, 13 PD], TTP based on 79% of events is 4.7 months in arm A and 4.2 months in arm B. Conclusions: Cetuximab can safely be added to the regimen of cisplatin and vinorelbine, with evidence suggesting enhancement of activity. No significant financial relationships to disclose.
P05 B-cell epitope mapping of anti-ro-52 responses in patients with primary biliary cirrhosis
Authors: M G Mytilinaiou, W Meyer, L Komorowski, C Probst, E Davies, D Vergani, D Bogdanos
Journal: Gut (2010)

Introduction  Up to 40% of patients with primary biliary cirrhosis (PBC) show reactivity against Ro-52 ( Hepatology  2009), a Sjogren9s syndrome (SS)-associated autoantibody. Previous studies have shown that anti-Ro-52 in SS targets the central, coiled-coil sequence of the 475-aa of the antigen. No study has dissected anti-Ro-52 reactivity in PBC.  Aim  To investigate anti-Ro-52 B-cell responses in patients with PBC and compare them with those obtained in patients with SS.  Method  Human recombinant full-length Ro-52 and 3 constructs spanning the whole protein were expressed in  E. coli  and tested for reactivity by a line immunoassay. Construct 1 (C1: aa1–129) contained the RING finger and the B-Box domains, construct 2 (C2: aa125–268) contained the coiled-coil domain and construct 3 (C3:aa 268–475) contained the B30.2/SPRY domain. Twenty-three 18-mer peptides overlapping by 12aa were synthesised and tested by an in house ELISA to better define the core epitopes within the highly immunogenic C2 region. Overall, 122 serum samples (68 from Ro-52 positive PBC patients, 39 from Ro-52 positive SS patients without liver disease and 15 from Ro-52 negative healthy blood donors) were tested.  Results  Reactivity to the C2 construct of Ro-52 was present in all Ro-52 positive sera from PBC and SS patients and in none of the controls (p  Conclusion  This is the first systematic B-cell mapping approach of anti-Ro-52 responses in PBC patients showing that the antigenicity of this protein lies within its coiled coil region. Two new epitopes, one of which dominant, have being discovered, both in PBC and SS. The fact that the fine epitope specificity of anti-Ro-52 is virtually identical in PBC and SS suggests a common mechanism of tolerance breakdown to this autoantigen in the two conditions.
Laparoscopic treatment of endometrial cancer: A cost-effectiveness analysis
Authors: L. N. Abaid, J. Boggess, J. Wu
Journal: Journal of Clinical Oncology (2006)

6127 Background: Endometrial cancer has traditionally been staged using an open abdominal incision. Laparoscopic staging offers the benefits of a minimally invasive approach and may also be economically advantageous. Methods: A decision model was developed to determine the cost-effectiveness of laparoscopy versus laparotomy for surgical staging of a hypothetical cohort of women, aged 35 to 80 years, with early-stage endometrial cancer. The analysis was performed from a societal perspective with a time horizon of six weeks. The primary outcome was cost-effectiveness, measured as cost per complete staging procedure. Parameters in the decision model included rates of mortality, intraoperative complications (bowel, bladder, or vascular injury and intraoperative hemorrhage), deep venous thrombosis (DVT), blood transfusion, and length of hospitalization. Assumptions included that laparoscopy and laparotomy were equally effective for staging, and that the length of hospitalization was one day for laparoscopy versus three days for laparotomy. Probability estimates were obtained from a review of the medical literature and from institutional data. Results: The cost for laparoscopic staging per subject was $14,616 compared to $16,184 for laparotomy. Thus, the incremental cost-effectiveness ratio (ICER) was $1,568 per complete staging procedure, and laparoscopy was more cost-effective than laparotomy. Based on one-way sensitivity analyses, the factor that had the greatest influence on the model was length of hospital stay after laparotomy. The ICER was insensitive to changes in the rates of mortality, intraoperative complications, and blood transfusions. Conclusions: Laparoscopic surgery for endometrial cancer is a cost-effective alternative to laparotomy, primarily because it reduces the length of the postoperative hospitalization. No significant financial relationships to disclose.
Are cisplatin and carboplatin equivalent in the treatment of non-small cell lung carcinoma (NSCLC)? Results of a comprehensive review of randomized studies in over 2300 patients
Authors: N. J. Zojwalla, H. Raftopoulos, R. J. Gralla
Journal: Journal of Clinical Oncology (2004)

7068 Background: Meta-analysis of the initial 8 trials of chemotherapy vs BSC (BMJ 1995) showed a small (6 week median) but significant (p=.001) benefit for chemotherapy. Cisplatin was the only agent identified contributing to improved survival. Standard chemotherapy for NSCLC is now considered to be a platinum-based two-agent regimen. Phase III comparisons of newer agent doublets (with paclitaxel, docetaxel, gemcitabine, vinorelbine) fail to show almost any survival differences among the newer drugs. (Schiller NEJM 2002, Kelly JCO 2001). However, some large phase III studies have recently indicated significant survival differences favoring cisplatin over carboplatin (Rosell Ann Oncol 2002, Fosella JCO 2003). Methods: To investigate these varying results, we conducted a comprehensive review of randomized studies which used the same new agent with only the platinum drug differing among the treatment arms. Inclusion criteria: all randomized trials published from 1992 to 2003. Median survivals for cisplatin and carboplatin arms in each study were calculated. Results: Five studies met the criteria, including 2306 patients randomized to either cisplatin (1154) or carboplatin (1152) with taxanes (paclitaxel in 2 studies, docetaxel in 1) and gemcitabine (2 studies). Prognostic factors were similar between platinum arms. For all studies, median survival for patients randomized to cisplatin regimens was 9.8 months (95% CI: 8.8–10.7 months), for carboplatin regimens 8.7 months (95% CI: 7.9–9.9 months). Conclusions: A modest but useful survival benefit favors cisplatin. This 5 week benefit is: 1) similar to the benefit of chemo over BSC with older regimens, 2) represents 25% of the chemo benefit over BSC in newer trials (Bria Proc ASCO 2002), and 3) comprises a more important benefit than the choice of the new agent in a doublet. Studies have not shown patient determined quality of life differences between platinums, and new antiemetics reduce acute emesis rates to <10%. These survival benefits warrant confirmation in a meta-analysis using individual patient results. No significant financial relationships to disclose.
Disenrollment from Medicare managed care: Does a cancer diagnosis make a difference?
Authors: E. B. Elkin, N. M. Ishill, G. F. Riley, P. B. Bach, M. Gonen, C. B. Begg, D. Schrag
Journal: Journal of Clinical Oncology (2008)

6582 Background: Medicare managed care (MMC) plans offer enrollees reduced cost-sharing and provide benefits that are not available in the traditional fee-for-service (FFS) program. However, MMC plans may restrict choice of providers in an effort to control costs. Access to specific providers may be of particular concern to enrollees with cancer. We compared rates of voluntary MMC disenrollment to FFS in beneficiaries with and without a new cancer diagnosis. Methods: We identified MMC enrollees aged 65 and older diagnosed with a first primary breast (n=28,331), colorectal (n=26,494), prostate (N=29,046) or lung (n=31,243) cancer in 1995–2002 from Surveillance, Epidemiology and End Results (SEER) cancer registry records linked with Medicare enrollment files. Cancer patients were pair-matched to cancer-free enrollees by age, sex, race and geographic location. We estimated rates of voluntary MMC disenrollment in the two years following each cancer patient's diagnosis. Hazard ratios for disenrollment, comparing beneficiaries with and without cancer, were stratified by matching characteristics and adjusted for plan type, plan tax status, county- level MMC penetration and year of diagnosis. Results: In the two years following diagnosis, cancer patients were less likely to disenroll from MMC than their matched cancer-free peers. Crude two-year disenrollment probabilities and adjusted hazard ratios for disenrollment are shown in the Table. Results were consistent across strata of age, sex, race, SEER registry and cancer stage. Beneficiaries in independent practice assocication plans and for-profit plans had an increased risk of disenrollment, regardless of cancer status. Conclusion: A new cancer diagnosis between 1995 and 2002 did not precipitate voluntary MMC disenrollment to FFS. These findings suggest that Medicare beneficiaries with cancer were satisfied with their managed care plans or were reluctant to change their insurance enrollment. Medicare Managed Care Disenrollment, Cancer vs. Cancer-Free Breast Colorectal Prostate Lung 2-yr % disenroll - cancer 10% 10% 13% 5% 2-yr % disenroll - cancer-free 13% 14% 14% 14% Adjusted HR, disenrollment (95% CI) 0.78 (0.74–0.82) 0.84 (0.80–0.88) 0.86 (0.82–0.90) 0.81 (0.76–0.86) No significant financial relationships to disclose.