tbuckley/cabot-search huggingface dataset:
HER-2, Hormone Receptors, and clinicopathologic characteristics in Uruguayan breast cancer patients
Authors: L. B. Delgado, R. Fresco, G. Santander, S. Aguiar, N. Camejo, L. Ferrero, V. González, S. Heinzen, A. Martinez, G. Sabini
Journal: Journal of Clinical Oncology (2009)

e22202 Background: Few Latin-American studies and none Uruguayan study have evaluated HER-2, estrogen receptor (ER) and progesterone receptor (PR) in breast cancer (BC). The purpose of the study was to investigate the frequency of these markers and the relationship between them and with clinicopathologic features in Uruguayan BC patients (pts). Methods: We retrospectively reviewed clinical records from pts who underwent curative surgery for stage I-III invasive BC at the Oncology Units of 4 institutions in Montevideo between march 2006 and march 2008. We obtained the following data: age, TNM, ER/PR status by immunohistochemistry (IHC) and HER2 status by IHC and FISH in HER2 IHC 2+. Fisher's exact test was used to analyze the data. Results: 427 pts were included. Median age was 60 years-old (range: 24–93 y), postmenopausal 75%, stages: I 33%, II 42%, III 23%, unknown 2%. ER/PR status was known in 94,6% of cases: ER+/PR+ 66,1%, ER+/PR- 11,1%, ER-/PR+ 3,5%, ER-/PR- 19,3%. HER2 status was known in 47% (199/427) of cases, being positive (IHC 3+ or FISH+) in 13.6%. Triple negative tumors were found in 32 of 199 pts (16%). HER2 was positive in 8% of pts with ER+ and/or PR+ tumors, and in 18% of pts with ER-PR- disease (p=0.08). We did not find a significant association between axillary lymph node status and HER2 status. Besides, triple negative BC did not correlate with axillary lymph node status. When analized by menopausal status, the frequency of triple negative pts was 14% in the premenopausal group and 4% in the postmenopausal group (p=0.005). In addition, the rate of triple negative BC was 0% in pts with histologic grade 1 and 10% in pts with histologic grade 2–3 (p = 0.0005). Conclusions: Our data from Uruguayan pts show a lower prevalence of HER2 positive but a similar prevalence of ER+ and PR+ operable BC than the prevalence reported in most American and European studies. In accordance with previous reports, triple negative BC correlated with younger age and higher histologic grade. No significant financial relationships to disclose.
Phase I/feasibility trial of dose-dense carboplatin (C) and paclitaxel (P) in patients (pts) with ovarian cancer: A Gynecologic Oncology Group study
Authors: A. Tiersten, M. Sill, F. Muggia, C. Elera, A. Garcia, P. Fracasso, R. Swensen, D. Warshal, R. Mannel
Journal: Journal of Clinical Oncology (2009)

5544 Background: Dose-dense regimens improve outcome for women with breast cancer. We investigated the feasibility of dose-dense CP for women with ovarian cancer. Methods: Pts with untreated stage III/IV ovarian cancer received C AUC 5 and P 175 mg/m2 day 1, pegfilgrastim 6 mg day 2 every 2 weeks for 6 cycles. Dose-limiting toxicity (DLT) was defined as: febrile neutropenia, grade 4 neutropenia ≥7 days, grade 4 thrombocytopenia (tcp), grade 3 tcp with bleeding, dose delay &gt;2 weeks, grade 3/4 non-hematologic toxicity (excluding fatigue, hypersensitivity, nausea/vomiting, alopecia, constipation, diarrhea or bone pain), and any treatment related death. The study utilized a 2-stage sequential design (20 pts/stage) with DLTs in 6 cycles determining regimen feasibility. Results: Between September 2006 and September 2008, 43 pts enrolled. Twenty and 17 patients were evaluable for toxicity over 6 cycles in stages 1 and 2 respectively. Six DLT's were observed for both stages. Thirty pts completed treatment and 12 did not [DLTs (6), paclitaxel hypersensitivity reactions (2), progression (1), patient choice (1), infection (1) and death unrelated to treatment (1)]. One pt remains on treatment. The 6 DLTs resulting in treatment discontinuation included grade 3 neuropathy (2), grade 4 neuropathy (1), grade 4 tcp (1), grade 4 tcp/grade 3 febrile neutropenia (1), and grade 4 SVT (1). Six other DLTs not preventing treatment completion included grade 3 infection (1), grade 3 AST/ALT elevation (1), grade 3 confusion (1), grade 3 dehydration (1), grade 3 neuropathy (1) and grade 4 tcp (1). Other toxicities resulting in treatment delays included grade 3 tcp (1), grade 3 fatigue (1) and grade 2 neuropathy (2). There were 5 P dose reductions and 4 C dose reductions. Conclusions: Seventy-two percent pts completed 6 cycles of dose-dense CP. Based on DLTs (at least 12 in 37 evaluable pts), this regimen is not feasible. Given the neuropathy and tcp, we do not recommend further investigation in a phase III trial. No significant financial relationships to disclose.
Combination Versus Sequential Doxorubicin and Docetaxel as Primary Chemotherapy for Breast Cancer: A Randomized Pilot Trial of the Hoosier Oncology Group
Authors: Kathy D. Miller, Worta McCaskill-Stevens, Judy Sisk, David M. Loesch, Frank Monaco, Roopa Seshadri, George W. Sledge
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the efficacy and toxicity of combination and sequential dose-dense chemotherapy with doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as primary chemotherapy of breast cancer. PATIENTS AND METHODS: Patients with newly diagnosed stage II or noninflammatory stage III breast cancer were randomly assigned to receive the same total doses of doxorubicin and docetaxel over a 12-week period before definitive surgery. Patients in arm A received sequential therapy with doxorubicin 75 mg/m 2 every 2 weeks for three cycles followed by docetaxel 100 mg/m 2 every 2 weeks for three cycles. Patients in arm B received combination therapy with doxorubicin 56 mg/m 2 plus docetaxel 75 mg/m 2 every 3 weeks for four cycles. Granulocyte colony-stimulating factor was administered on days 2 to 12 of each cycle in both groups. RESULTS: Forty patients were entered onto the trial. Pretreatment tumor size averaged 5.7 cm with clinicallypositive axillary lymph nodes in 23 patients (57%). As expected, myelosuppression was severe in both groups; however, ≥ 80% of planned dose-intensity was delivered. Hand-foot syndrome was more common after sequential therapy. Clinical responses were similar in both groups, with an overall response rate of 87%, including 20% clinical complete remissions. Pathologic complete remission or residual in situ disease only was confirmed in five patients (12.8%). Patients who received sequential therapy had fewer positive lymph nodes (mean, 2.17 v 4.81; P &lt; .037) at definitive surgery. CONCLUSION: Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active. A sequential treatment schedule increases toxicity but may result in more substantial lymph node clearance than combination therapy.
Sequential therapy for locally advanced larynx and hypopharynx cancer: Subgroup analysis from the TAX 324 Study
Authors: M. R. Posner, C. M. Norris, R. B. Tishler, L. J. Wirth, R. I. Haddad
Journal: Journal of Clinical Oncology (2008)

6031 Background: The Phase III Tax 324 trial compared sequential therapy (ST) with induction docetaxel, cisplatin and 5-fluorouracil (TPF) to cisplatin and 5-fluorouracil (PF) with both followed by chemoradiotherapy (CRT) with weekly carboplatin. Locally advanced larynx (LX) and hypopharynx (HPX) cancers represent an important subgroup in which laryngectomy free survival (LFS), as well as overall survival (OS), and progression free survival (PFS), are cardinal endpoints. Methods: All patients (pts) with LX or HPX cancer enrolled in TAX 324 were identified. Data were extracted from Case Report Forms and analyzed as described. LFS was defined as pts with operable disease and alive with no primary site surgery. Details of treatment and overall safety have been previously reported (Posner et al, NEJM, 2007). Results: Of 501 evaluable pts, 89 and 77 had LX or HPX cancer, respectively. Of these 166, 90 were randomized to TPF and 76 to PF. There were no significant differences between the two arms with regard to age, sex, site of disease, PS, resectability, or nodal stage. With 41 months (mo) median follow-up, median OS is 59 (31-NR) vs. 24 (13–42) mo and the Hazard Ratio (HR) for mortality is 0.62 (0.41- 0.94, p= 0.02); the median PFS is 21 (12–58) vs. 11 (8–14) mo and the HR is 0.66 (0.45–0.97, p = 0.03), for TPF and PF, respectively. Among 67 and 56 operable pts in the TPF and PF arms, respectively, LFS was significantly greater with TPF; the HR is 0.59 (0.37–0.95, p = 0.03). The 3-year LFS is 52% (39–65%) vs. 32% (19–45%) favoring TPF. Conclusions: Among pts with locally advanced LX and HPX cancer, ST with TPF results in a significant reduction in mortality (p =0.02) and improvement in PFS (p = 0.03), compared to PF. Among operable pts, there is a significant improvement in LFS with TPF (p = 0.03). With the results of previous phase III trials showing equivalence for LFS and OS with PF or CRT, these results support the use ST with TPF and carboplatin/CRT as another acceptable treatment option for organ preservation in LX and HPX cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis
A phase I/II study of telomerase peptide vaccination in combination with chemotherapy in patients with stage IV malignant melanoma
Authors: S. Aamdal, S. Dueland, O. Engebraaten, K. Owre, M. Dyrhaug, S. Trachsel, G. Gaudernack
Journal: Journal of Clinical Oncology (2006)

8031 Background: A phase I/II feasibility study was conducted to investigate the safety, tolerability and immunological response to vaccination with the telomerase peptide GV1001 (hTERT: 611–626) in combination with temozolomide (T). Methods: Twenty-five patients with malignant melanoma (15 stage M1c,10 stage M1b) received T day 1–5 every four weeks for 1–9 cycles. During the first cycle (4 weeks) they received i.d. injections of 560 μg GV1001 with local GM-CSF in week 2,3 and 4, followed by injections in week 6 and 7 in the second cycle and week 11 in the third cycle. The treatment period was 12 weeks (3 cycles). Booster vaccinations with 560 μg GV1001 were offered every third month. Monitoring of blood samples, clinical examination were performed regularly with radiological staging every 12 th week. Immune responses were measured as DTH and in vitro T-cell proliferation. Results: The treatment was generally well tolerated with only grade 1–2 toxicity in most patients. Of 14 patients, 4 developed grade 3 toxicity and one grade 4 toxicity (neutropenia). Immune responses against GV1001 were detected in 17/21 patients (81%) at 12 weeks. Patients receiving up to 9 cycles of T exhibited stable proliferative responses to GV1001 throughout the treatment period. None of the patients had DTH response at trial entry and no DTH responses were observed in patients receiving T. This was not due to a shift in the cytokine profile since cloned GV1001-specific CD4+ T cells displayed a Th1 cytokine profile. Upon evaluation in week 12, 6 patients had SD, 10 PD. One patient had a PR with shrinkage or disappearance of multiple lung metastases. A patient continuing on vaccine alone developed significant DTH response when T therapy was stopped. Conclusions: Telomerase vaccination of patients receiving concomitant T treatment is feasible. The unexpected high proportion of patients showing an immune response indicates that regulatory T-cells may have been removed by T treatment. The chemotherapy may also have influenced effector cells required for development of skin reactions. In spite of lacking DTH response however, the majority of the patients demonstrated significant immune response indicating different regulation of DTH and T-cell response. No significant financial relationships to disclose.
R-CHOP-14 in patients with diffuse large-B-cell lymphoma (DLBCL) younger than 70 years: A multicentric and prospective study
Authors: A. Rueda, P. Sabin, J. Rifá, M. Llanos, J. Gómez-Codina, F. Lobo, R. García-Arroyo, J. Herrero, M. Provencio, C. Jara
Journal: Journal of Clinical Oncology (2006)

7592 Background: Several studies have shown that the addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisona), or shortening the interval between cycles of chemotherapy to two weeks, improves survival of patients with DLBCL. These studies prompted our group (GOTEL) to evaluate in a prospective study, the feasibility and efficacy of R-CHOP-14 in patients (pts) with DLBCL. Methods: Patients (younger than 70 years) with stage II bulky, III or IV DLBCL, and no significant co-morbidities were included in the study. R was administered on day 1 before chemotherapy. R-CHOP was recycled every 14 days. No antimicrobial prophylaxis was administered. All pts received filgrastim (5 μg/kg) from day +3 to +10. Pts received 6 cycles if CR was achieved after 3 cycles; those in PR, and those pts with bone marrow disease at diagnosis, received 8 cycles. Involved field radiation therapy was permitted for pts with stage II bulky disease. Results: From May 2002 to august 2004, 77 pts were included. Median age was 54 years (range, 15–70); 55 patients were younger than 60 years. According to the age adjusted International Prognostic Index (aaIPI), 13 pts (17%) had low risk disease, 27 pts (35%) low-intermediate risk, 29 pts (38%) high-intermediate risk, and 8 pts (10%) high risk disease. Grade 3–4 toxicity occurred as follow: neutropenia in 15 pts (19%), anaemia in 7 pts (9%), thrombocytopenia in 4 pts (5%), mucositis in 4 pts (5%) and peripheral neurotoxicity in 4 pts (5%). Ten pts were hospitalized (febrile neutropenia: 8 cases, one case of gastric perforation and one pulmonary embolism). After therapy, 61 pts (79%) achieved a CR/CRu (C.I. 95%: 57%-90%) and 14 pts (18%) a PR. 2 pts (3%) had refractory disease. With a median follow-up of 20 months, progression-free and overall survival at 24 months were 68% and 87%, respectively. Conclusions: Administration of R-CHOP-14 (with filgrastim support) is feasible and effective in patients younger than 70 years. [Table: see text]
Darbepoetin alfa administered at varying intervals compared with weekly epoetin alfa for treating chemotherapy-induced anemia: A pooled analysis of 20 clinical trials
Authors: J. Glaspy, D. Henry, J. L. Canon, H. Lam, T. Lillie
Journal: Journal of Clinical Oncology (2006)

18508 Background: Cancer patients (pts) often develop chemotherapy-induced anemia (CIA), resulting in an increased risk for transfusions and fatigue. The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) can reduce transfusion requirements, raise hemoglobin (Hb) levels, and decrease fatigue in pts with CIA. The 74-hour half-life of DA allows for flexible dosing with weekly (QW), every-2-week (Q2W), or every-3-week (Q3W) administration. This study evaluated if the dosing interval used to administer DA affected its efficacy. Methods: Data from 20 clinical trials in the CIA setting were pooled, including single-arm, active-controlled, and placebo-controlled trials (a full description of these studies will be presented). Six studies contributed data for DA QW, 7 studies for DA Q2W, and 5 studies for DA Q3W. Controlled studies used either a placebo or EA as the comparator. Logistic regression with treatment as a random effect was used to analyze the clinical trials. Endpoints included the percentage of pts requiring transfusions (from week 1 to end of the treatment period [EOTP] and from week 5 to EOTP), reaching a target Hb of ≥ 11 g/dL, and achieving ≥ 3 point change in FACT-F score from baseline (BL). Percentages were adjusted for BL Hb levels (&lt; 10 vs ≥ 10 g/dL), whether pts received platinum chemotherapy (no vs yes), and for dosage adjustments. Results: The type of ESA used (EA or DA) did not appear to affect the percentage of study pts who achieved clinically meaningful endpoints (see Table ). The results from these analyses also suggest that the dosing interval at which DA was administered did not affect its efficacy in study pts (see Table ). Conclusions: DA administered at dosing intervals of QW, Q2W, or Q3W has comparable efficacy to EA QW. This flexibility allows DA administration to be synchronized with common chemotherapy schedules, which may increase pt convenience by reducing the number of clinic visits. [Table: see text] [Table: see text]
<i>In vitro</i> chemosensitivity to gemcitabine, oxaliplatin and zoledronic acid predicts treatment response in metastatic gastric cancer - a case report
Authors: J. Trojan, S. Z. Kim, K. Engels, S. Kriener, P. S. Mitrou, K. U. Chow
Journal: Journal of Clinical Oncology (2005)

2122 Background: Individual response of disseminated cancer to chemotherapy is unpredictable. In vitrochemotherapy induced apoptosis can be measured and might be a method to evaluate in vivoactivity of tested drugs. Methods: In this report, tumor cells of a patient with signet-cell carcinoma of the stomach and diffuse bone marrow infiltration were cultured and tested for in vitrochemosensitivity. Tumour cells were selected by a ficoll gradient, cultured and incubated with cytotoxic agents in various concentrations and combinations for 24 hours. The percentage of apoptotic cells was assessed by flow-cytometry using Annexin V. Results: The drugs gemcitabine, oxaliplatin and zoledronic acid were found to induce in vitrotumor cell apoptosis synergistically. According to the results of the in vitro chemosensitivity testing, the patient started a combination chemotherapy with a fixed-dose rate regimen of gemcitabine (1000 mg/m2 as a 10 mg/m2/min infusion on day 1) and oxaliplatin (100 mg/m2 as a 2-hour infusion on day 2), which was repeated every 2 weeks. Additionally, the patient received a biweekly infusion of the bisphosphonate zoledronic acid (4 mg, day 1). An initially existing disseminated intravascular coagulopathy quickly resolved, and after 6 months of treatment a still lasting complete response was induced, thus confirming the results of in vitrochemosensitivity testing. Conclusions: In vitrochemosensitivity testing might be very helpful to predict chemotherapy response in selected patients with metastatic gastric cancer. No significant financial relationships to disclose.
Detection of rearranged immunoglobulin DNA in plasma
Authors: L. Lin, C. Gocke, R. F. Ambinder
Journal: Journal of Clinical Oncology (2006)

17518 Background: Tumor DNA is increasingly recognized as a marker in plasma or serum. B cells are characterized by immunoglobulin heavy chain rearrangements (IgH-R)and B cell malignancies by clonal IgH-R. We hypothesized that detection of clonal IgH-R DNA (a DNA spike) might reflect the presence of malignancy. Methods: We used a PCR and capillary electrophoresis. DNA from plasma of 6 healthy donors, 5 patients treated with rituximab, 5 persons with AIDS (PWA) but not lymphoma, 5 patients with AIDS-related lymphoma (ARL) and 5 patients with Hodgkin’s lymphoma (HL) was studied. In some cases matched peripheral blood mononuclear cells (PBMC) and followup specimens were available. Results: In plasma from healthy donors there was a normal (bell-shaped) distribution of IgH-R. In patients treated with rituximab (including a patient with an autoimmune disorder but no malignancy), IgH-R in plasma decreased by at least 100-fold. In PWA, there was a normal distribution of IgH-R. In pretreatment plasma from 2 of 5 patients with ARL, a DNA spike was detected superimposed on the background of IgH-R. The DNA spike was not detected in PBMC. In both ARL patients the spikes disappeared with therapy. However, in 1 it reappeared, and shortly thereafter the patient relapsed. Clinical relapse was associated with an increase in spike amplitude. The spike disappeared again with salvage chemotherapy. Identity of the pretreatment and relapse spikes was confirmed by sequencing. In 1 of 5 patients with HL a pretreatment DNA spike was detected in plasma. It decreased in serial specimens during the first month of combination chemotherapy. Conclusions: A normal distribution of rearranged Ig DNA is readily detected in plasma from healthy donors and patients. This normally distributed rearranged Ig DNA consistently disappears with rituximab therapy. A DNA spike can be detected in the plasma of some patients with B lineage lymphoma even when that spike is not evident in PBMC consistent with the possibility that this DNA is not derived from circulating tumor cells. The reappearance of a DNA spike may presage relapse. Further investigation will be required to determine the sensitivity and specificity of detection of such Ig DNA spikes and to confirm a tumor origin. No significant financial relationships to disclose.
Examining minimal perceptible clinical improvement criteria in patients treated with hylan G-F-20 for knee osteoarthritis
Authors: N. Bellamy, M. J. Bell, C. H. Goldsmith, G.W. Torrance, J. Raynauld, P. Tugwell, R. Polisson, D. Pericak, V. Walker
Journal: Annals of the Rheumatic Diseases (2004)
Preclinical development of orally available sphingosine kinase inhibitors
Authors: C. D. Smith, L. W. Maines, Y. Zhuang, C. L. Green, S. N. Keller, V. Beljanski, C. Knaak, W. Wang
Journal: Journal of Clinical Oncology (2009)

e14615 Background: Sphingolipid-metabolizing enzymes control the dynamic balance of important bioactive lipids, including apoptotic ceramide and proliferative sphingosine 1-phosphate (S1P). Several growth factors and inflammatory cytokines promote the cleavage of sphingomyelin and ceramide leading to rapid elevation of S1P levels through the action of sphingosine kinases (SKs). SK1 is oncogenic and is markedly overexpressed in a variety of human cancers, making this enzyme a potential molecular target for cancer therapy. Methods: SK inhibitors were synthesized and evaluated in a variety of cellular and in vivo models. Antitumor activity was assessed in an allogeneic model utilizing murine JC mammary adenocarcinoma cells growing in Balb/c mice, and a xenograft model of human Bxpc pancreatic adenocarcinoma cells growing in scid-mice. Results: The lead SK inhibitors, called ABC294640 and ABC294735, inhibit SK1 and SK2 at low micromolar concentrations, and are nontoxic to rodents at acute doses up to at least 1000 mg/kg (po). ABC294640 is orally-available, and has excellent pharmacokinetics, with serum levels exceeding the effective SK inhibitory concentration for at least 8 hours. Acute- and chronic- toxicology studies indicate that ABC294640 induces a transient minor decrease in the hemotocrit of rats and mice receiving 100 and 250 mg/kg/day; however, this normalizes by 28 days of treatment. No other changes in hematology parameters, or gross or microscopic tissue pathology result from treatment with ABC294640. Oral administration of ABC294640 to mice bearing JC adenocarcinomas results in dose-dependent antitumor activity associated with depletion of S1P levels in the tumors and progressive tumor cell apoptosis. ABC294735 is also orally-active in both JC and Bxpc tumor models, and demonstrates synergistic antitumor activity when combined with cisplatin or gemcitabine. Conclusions: These newly developed SK inhibitors provide orally-available drug candidates for the treatment of pancreatic cancer and other diseases. IND-enabling CMC and toxicology work is currently underway, and an SK inhibitor is expected to enter clinical trials in early 2010. [Table: see text]