tbuckley/cabot-search huggingface dataset:
HER-2/<i>neu</i> overexpression and its effect on survival in solid tumors
Authors: K. Tendulkar, A. K. Ganti, V. Koka, M. Koch, A. Potti
Journal: Journal of Clinical Oncology (2004)

9559 Background: Overexpression of HER-2/neu in breast cancer is associated with an adverse outcome. Little definitive data exists in other solid tumors. We studied the prevalence and predictive role of overexpression of HER-2/neu in >1200 samples obtained from patients with extensive stage small cell lung cancer (ESSCLC), malignant melanoma, pancreatic carcinoma, hepatocellular carcinoma, malignant brain tumors and soft tissue sarcomas (STS). Methods: HER-2/neu overexpression was assessed by immunohistochemistry (IHC) (DAKO Hercep test) performed on archival paraffin-embedded tissue specimens. A trained pathologist, who was blinded from the clinical history, interpreted all the results. An IHC score of >/= 2+ was considered positive for overexpression. Results: HER-2/neu overexpression by tumor type and its effects on survival are shown in Table 1. Studying large cohorts of patients with pancreatic adenocarcinoma and STS [except malignant fibrous histiocytoma (MFH), dermatofibrosarcoma (DFS) and carcinosarcomas (CS)] did not reveal a role for HER-2/neu testing. However in ESSCLC, the median survival for patients who were HER-2/neu +ve was 8 months (range: 1–25.5) while that in the HER-2/neu -ve group was 16 months (range: 2–34) (p<0.001, Mann Whitney U test). Furthermore, amongst patients with glioblastoma multiforme (GBM), median survival for patients who were HER-2/neu +ve was 4 months compared to 8 months in those who were HER-2/neu -ve. In addition, HER-2/neu overexpression increased the odds of early mortality (<3 months) (p<0.01). Conclusions: HER-2/neu overexpression seems to be associated with a poor prognosis in ESSCLC, STS and GBM. HER-2/neu overexpression is not uniform in all STS. Unlike other sarcomas, MFH, DFS and CS are more likely to overexpress HER-2/neu. HER-2/neu overexpression is not seen/has no clinical value in hepatocellular carcinoma, pancreatic adenocarcinoma or malignant melanoma. No significant financial relationships to disclose.
Phase II study of oblimersen sodium and rituximab in patients with recurrent B-cell non-Hodgkin’s lymphoma
Authors: B. Pro, M. R. Smith, B. Leber, A. Younes, L. Fayad, F. B. Hagemeister, P. McLaughlin, A. M. Rodriguez, Y. Caddick, J. A. Zwiebel
Journal: Journal of Clinical Oncology (2005)

6611 Background: Oblimersen sodium (Genasense;GNS) is an 18-mer oligonucleotide that targets the mRNA of Bcl-2, a protein that inhibits apoptosis and confers treatment resistance. GNS has shown marked activity in xenograft models of non-Hodgkin’s lymphoma (NHL) and enhances the antitumor activity of rituximab (RIT). We are conducting a phase II study to determine the efficacy and toxicity of GNS + RIT in patients (pts) with recurrent B-cell NHL. Methods: GNS (3mg/kg/d) was administered as continuous IV infusion for seven days in weeks 1,3, and 5 (d1–7,15–21,29–35). RIT (375 mg/m2) was given weekly for 6 doses (d3,8,15,22,29,36). Patients whose disease did not progress were allowed to receive one additional cycle. Prior exposure to rituximab was permitted. Results: To date 29 have been enrolled. Thirteen pts had follicular lymphoma (FL), 5 large cell lymphoma (LCL), 5 small lymphocytic lymphoma (SLL), 3 mantle cell lymphoma (MCL), 2 mucosa-associated lymphoid tissue (MALT) lymphoma, and one B-cell lymphoma not further classified (NOS). Median number of prior treatments was 2 (range 1–3). Twenty-one pts are evaluable for response and toxicity. Eight pts (38%) responded to the combination therapy, 2 pts achieved a CR (1 MALT, 1 FL), 1 pt achieved an unconfirmed CR (FL), 5 pts achieved a PR (1 MCL, 2 FLCL, 1 SLL, 1FL). Two of the responses (1 CR,1 PR) were observed in rituximab-refractory pts. Common grade 3–4 toxicities included: reversible neutropenia in 7 pts (33%), thrombocytopenia in 2 pts (9%), non-neutropenic fever in 4 pts (19%). Conclusions: GNS can be safely combined with RIT and appears to be an active combination in recurrent B-cell lymphomas. Patients accrual is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech
Role of autologous stem cell transplant after induction therapy with bortezomib-lenolidomide or bortezomib-thalidomide in newly diagnosed multiple myeloma patients
Authors: N. Shah, D. Weber, R. Orlowski, M. Wang, S. K. Thomas, T. Richards, S. Giralt, M. Qazilbash, R. Alexanian, J. J. Shah
Journal: Journal of Clinical Oncology (2009)

8596 Background: The introduction of novel therapeutic options with bortezomib and immunomodulatory agents in the up-front management of multiple myeloma (MM) has significantly improved induction response rates. However, the role of high dose chemotherapy and autologous stem cell transplant (ASCT) after induction with these highly active agents is not known, especially in patients with only a partial response to induction therapy. Methods: We conducted a retrospective review of 95 newly diagnosed MM patients treated with induction bortezomib-lenolidomide-dexamethasone (BLD) or bortezomib-thalidomide-dexamethasone (BTD) prior to ASCT. Responses were graded according to IMWG criteria. Results: 19 patients received BLD and 76 patients received BTD. All patients were conditioned with a melphalan-based regimen. Of the 19 patients who underwent induction with BLD, complete response (CR), very good partial response (VGPR) and partial response (PR) were achieved in 2 (11%), 8 (42%) and 9 (47%) respectively for an overall response rate (ORR) of 19/19 (100%). After ASCT, CR, VGPR and PR were achieved in 9 (47%), 5 (26%) and 5 (26%) respectively for a continued ORR of 21/21 (100%). Notably, 4/8 (50%) of patients with a VGPR after induction therapy with BLD improved to a CR after ASCT. 3/9 (33%) of patients with an initial PR to BLD improved to a CR and 1/9 (11%) with a PR improved to VGPR after ASCT. Of the 76 patients who underwent induction with BTD, CR, VGPR and PR were achieved in 6 (8%), 37 (49%) and 31(41%) respectively for an ORR of 74/76 (97%). 1 patient had stable disease and 1 patient had progressive disease. After ASCT, 27/76 (36%) achieved a CR, 30/76 (39%) a VGPR and 18/76 (24%) a PR for an ORR of 75/76 (99%). Of the patients who initially had a VGPR to BTD 16/37 (43%) improved to a CR while 5/32(16%)of PR patients improved to a CR and 9/32 (28%) of PR patients improved to a VGPR. Conclusions: Of the 40 patients who only achieved a PR after induction therapy with BLD or BTD, 16 (40%) had further improvement to a CR or VGPR after ASCT. Thus there is a significant benefit of ASCT in these patients who initially demonstrate relative resistance to induction therapy with highly active regimens. [Table: see text]
Final results of a phase III randomized study of concurrent weekly cisplatin-RT versus RT alone in locoregionally advanced nasopharyngeal carcinoma (NPC)
Authors: A. T. Chan, R. Ngan, P. Teo, S. F. Leung, H. Y. Yiu, W. Yeo, T. Mok, F. Y. Cheung, W. Kwan, B. Zee
Journal: Journal of Clinical Oncology (2004)

5523 Background/Objective: NPC is highly radiosensitive and chemosensitive. 3 cycles of 3-weekly chemotherapy concurrent with RT followed by 3 cycles of adjuvant chemotherapy has improved survival over RT alone in a previous randomized study. The regimen was associated with significant toxicities. This randomized phase III study compared concurrent weekly cisplatin-RT with RT alone in patients with locoregionally advanced NPC. Methods: Patients with Ho's N2 or N3 stage or N1 stage with nodal size ≥ 4 cm were randomized to receive cisplatin 40 mg/m2 weekly up to 8 weeks concurrently with RT (CRT) or RT alone. The primary endpoints are progression-free survival (PFS) and overall survival (OS). Results: 350 eligible patients were randomized. Baseline patient characteristics, treatment toxicities and PFS analysis at median follow up of 2.71 years have been published previously. At a median follow up of 5.5 years where 58 and 73 deaths were found out of 174 CRT and 176 RT patients respectively (95th and 5th percentiles ranging from 3.8 to 8.7 years respectively), the 5 year PFS was 62% for the CRT arm and 52% for the RT arm (p=0.0764 with a hazards ratio of 1.33 and a 95% C.I. 0.97 to 1.84). The 5 year OS was 72% for the CRT arm and 59% for the RT arm (p=0.0479) with a hazards ratio of 1.41 (95% C.I. 1.00 to 2.00). Using Cox regression analysis, male sex (p=0.0284), advanced Ho's T (p=0.0002) and advanced age (p=0.0019) had poorer prognoses. The treatment-by-covariate interaction effect was not significant under the Cox model (p=0.1122, 3 d.f.). The treatment effect on OS remains borderline significant in favor of CRT (p=0.0586, with hazards ratio of 1.40 with 95% C.I. 0.99 to 1.97) after adjusting for significant covariates. There were no treatment-related deaths. In the CRT arm, 4.6% of patients had grade 4 mucositis and 12.6% of patients had grade 3 leukopenia. Conclusion: Weekly cisplatin-RT is well tolerated in patients with advanced NPC in endemic areas and is associated with clinically significant improvement in PFS and OS. This regime can be offered as standard treatment in locoregionally advanced NPC. No significant financial relationships to disclose.
Oral vinorelbine in combination with capecitabine in advanced breast cancer
Authors: M. Gil-Delgado, H. Boostan, E. Garcia-Giralt, G. Auclair, F. Biville, D. Khayat
Journal: Journal of Clinical Oncology (2006)

10586 Background: the availability of chemotherapeutic drugs given by oral route represents a step forward in the management of cancer patients (pts). Vinorelbine and capecitabine have demonstrated established efficacy in metastatic breast cancer (MBC) with distinct mechanism of action. Oral vinorelbine (OVRL) interacts with tubulin and capecitabine (XLD) acts through antimetabolite properties of 5FU. OVRL is rapidly absorbed (1.5- 3h) with elimination half-life around of 40h. No pharmacokinetic interaction was found between these two compounds and its metabolites according to a recent phase I trial. Methods: The treatment schedule was 60 mg/m 2 of OVRL on day 1 and 8; XLD 1000 mg/ m 2 bid from day 1 to 14 every 3 weeks. Cycles were repeated if ≥1000/mm 3 neutrophils and ≥100000 platelets. In case of ≥ Grade (G) 3 haematological and non haematological toxicity dose adjustments were planned: OVRL from 60 mg/ m 2 50 or 40 mg/ m 2 and XLD from 1000 mg/ m 2 to 900 mg/m 2 or 750 mg/ m 2 b.i.d. Results: Between June 2003 to December 2005, 29 advanced breast cancer pts were included in this trial. Median age: 64 years [range (42–85)]. PS0: 60, PS1: 40. Eight pts, 9 pts and 12 pts received the combination as 1 st line, 2 nd line and ≥3 rd line treatment respectively. A median of 5 cycles [1–30] was given. No G 3/4 haematological toxicity was observed. One pt. suffered from G3 diarrhoea, G2 mild diarrhoea and abdominal pain was reported after ORVRL lasting 24 hours. No hand-foot syndrome has been observed.Out of 18 evaluable pts, 17 had clinical benefit: 1 CR, 4 PR and 12 SD (90% of tumour control). Conclusion: Oral vinorelbine and capecitabine combination is well tolerated and active in MCB pts allowing long-term treatment in ambulatory setting avoiding central venous line and infusions; therefore, this combination should be investigated in early lines of treatment. Final results will be presented during the meeting. [Table: see text]
Exome Sequencing Identifies a GNPAT Variant Associated with Severe Iron Overload in HFE C282Y Homozygous Men with Extreme Phenotypes; Possible Role in Regulation of Hepcidin Expression
Authors: Gordon D. McLaren, Mary J. Emond, V. Nathan Subramaniam, Pradyumna D. Phatak, James C. Barton, Paul C. Adams, Justin B. Goh, Cameron J. McDonald, Lawrie W. Powell, Lyle C. Gurrin, Katrina J. Allen, Deborah A. Nickerson, Tin Louie, Grant A. Ramm, Gregory J. Anderson, Christine E. McLaren
Journal: Blood (2014)
Molecular analysis-directed individualized therapy (MADeIT) in advanced non-small cell lung cancer (NSCLC)
Authors: G. R. Simon, C. C. Williams, A. A. Chiappori, E. B. Haura, T. Tanvetyanon, S. J. Antonia, G. Bepler
Journal: Journal of Clinical Oncology (2007)

7502 Background: RRM1 (R1) is a crucial gene for nucleotide metabolism, and it is the dominant molecular determinant of gemcitabine efficacy. ERCC1 (E1), a component of the nucleotide excision repair complex, is important for platinum-induced DNA adduct repair. We hypothesized that selection of dual agent chemotherapy based on tumoral R1 and E1 expression would be feasible and beneficial for patients with advanced NSCLC. Methods: A prospective phase II clinical trial in patients with advanced NSCLC was conducted. Patients were required to have a dedicated tumor biopsy for determination of R1 and E1 gene expression by real-time quantitative RT-PCR. The primers and probes had been validated by sequencing of cDNA amplicons. Dual agent chemotherapy consisting of carboplatin (C), gemcitabine (G), docetaxel (D), and vinorelbine (V) was selected based on gene expression as follows: GC for low R1/low E1; GD for low R1/high E1; DC for high R1/low E1; and DV for high R1/high E1. Eligibility included pathologically confirmed advanced NSCLC (stage IV and wet IIIB); PS 0–1; no prior systemic therapy for NSCLC; age ≥18; adequate hematologic, hepatic, and renal function; and measurable or evaluable disease by RECIST. Disease response and patient survival were measured. Results: Sixty eligible patients were enrolled from 2/04 to 12/05. Tumor specimens were collected in all with one minor and clinically insignificant complication. Expression analysis was successful in 55 patients. R1 expression ranged from 0–1,637; E1 expression ranged from 1–8,103; and their expression was correlated (Spearman's rho=0.46, p&lt;0.01). The partial response rate was 44% (95% CI 31–59%). OS and PFS and were 59% and 14% at 12 months with medians of 13.3 and 6.6 months respectively. Conclusion: Therapeutic decision making based on RRM1 and ERCC1 gene expression for patients with advanced NSCLC is feasible and promising for improvement in patient outcome. No significant financial relationships to disclose.
Cytokeratin positive cells in bone marrow, tumor biologic parameters of the primary tumor and survival in breast cancer patients
Authors: G. Gebauer, T. Fehm, H. Maul, P. Baier, A. Scharf, C. Sohn, W. Jaeger
Journal: Journal of Clinical Oncology (2004)

9517 Background: The presence of cytokeratin (CK) positive cells in bone marrow of breast cancer patients is correlated with worse clinical outcome. Therefore these cells were suggested to be derived from the primary tumor and are considered to represent an early metastatic tumor cell spread. Presence of these cells may be associated with highly aggressive breast cancer. We analyzed tumorbiologic parameters in the primary cancer, their correlation to the presence of CK positive cells in bone marrow, and survival of breast cancer patients with locally restricted disease. Methods: Bone marrow aspirates of 508 patients with operable breast cancer were analyzed for the presence of CK positive cells. Tissue samples of the primary tumor of 134 patients were analyzed for Ki-67, S-phase fraction, Her-2, estrogen, and progesterone receptor expression. Follow-up data were available for up to 11.2 years (median 9.5 years). Tumorbiologic factors were correlated to bone marrow status and disease-free and overall survival of the patients using chi square and log rank test. Results: 230 out of 508 patients were 'bone marrow positive' (45%). Presence of CK positive cells was negatively correlated to overall and disease-free survival (p< 0.001). Tumorbiologic parameters such as Ki-67, S-phase-fraction, steroid receptor status was also correlated to survival, however, there was no association of tumorbiologic factors and CK positive cells in bone marrow. Conclusions: Presence of CK positive cells in bone marrow of breast cancer patients is independent from characteristics of the primary cancer. This supports the hypothesis of tumor cell dormancy characterized by persistence of these cells after adjuvant therapy and late tumor relapse. No significant financial relationships to disclose.
An Active Hemovigilance Program Characterizing the Safety Profile of 7,437 Platelet Transfusions Prepared with Photochemical Treatment (INTERCEPT™).
Authors: J.C. Osselaer, J.P. Cazenave, C. Waller, M. Lambermont, O. Garraud, P. Fabrigli, M. Hidajat, D. Dehenau, L. Barbolla, J.L. Arroyo, R. Tardivel, M. Jacquet, D. Sundin, Lily Lin, L. Corash
Journal: Blood (2007)
Phase II study of oxaliplatin-based chemotherapy in patients with advanced gastric cancer
Authors: E. Vattemi, R. Pedersini, B. Kildani, J. Stocker, S. Baier, E. Cretella, M. Petric, M. Lusso, C. Graiff
Journal: Journal of Clinical Oncology (2006)

14119 Background: The aim of the study was to assess the toxicity and the clinical activity of oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks in patients with advanced gastric cancer. Methods: 26 patients with recurrent and/or metastatic gastric cancer were enrolled. They received oxaliplatin 85 mg/mq on day 1, FA 200 mg/mq as a 2 h infusion followed by bolus 5-FU 400 mg/mq repeated for 2 consecutive days (FOLFOX-4). Treatment was repeated every two weeks until disease progression or limiting toxicity. Results: Patients had a median age of 62 years (range, 74–40); 19 patients had a PS of 0–1. Twenty patients had a newly diagnosed metastatic disease and 6 patients had recurrent disease. The median number of sites involved was 2. Four patients had prior adjuvant chemotherapy with cisplatin, 5-FU and epirubicin. So far, 22 of 26 patients are evaluable. The mean number of cycles was 8.6 (range, 2–15). One complete response (4.5%) and 9 partial responses (41%) were observed for an overall response rate of 45%. Stable disease was seen in 8 patients (36%) and disease progression occurred in 4 patients (18%) Median progression free survival was 4.7 months and median overall survival was 9.8 months. No WHO grade IV toxicity occurred and the only grade III toxicity was peripheral neuropaty (10%). The most commonly reported hematologic event was grade II neutropenia (20%) and trombocytopenia (15%). Conclusions: FOLFOX-4 regimen shows good efficacy and accetable safety profile in advanced gastric patients. No significant financial relationships to disclose.
A phase II study of ABT-510 for the treatment of metastatic melanoma
Authors: S. Markovic, V. Suman, R. Rao, E. Creagan, W. Maples, J. Kaur, R. McWilliams, J. Allred, H. Pitot, G. Croghan, R. Humerickhouse
Journal: Journal of Clinical Oncology (2006)

8041 Background: ABT-510 is a synthetic peptide analog of thrombospondin-1 demonstrating inhibition of VEGF/bFGF mediated human endothelial cell migration, proliferation, tube formation, cornea-neovascularization as well as inhibition of tumor growth in vivo (B16F10 melanoma). Having been found to be safe in phase I testing, ABT-510 has entered phase II trials. Presented are the results of a phase II study using ABT-510 for the treatment of stage IV melanoma. Methods: A two stage phase II clinical trial was conducted to assess the anti-tumor activity, safety profile and pharmacodynamics of ABT510 in patients with stage IV melanoma. Patients self-administered 100mg of ABT-510 subcutaneously twice/day. Therapy was continued in the absence of excessive toxicity or tumor progression. Primary endpoint was 18 week progression free survival rate. Enrolled were patients at least 18 years of age with measurable (RECIST) metastatic melanoma, ECOG performance status of 0–2 and normal pre-registration blood tests. Exclusion criteria included: cancer therapy less than 4 weeks prior to registration; failure to recover from prior therapy; brain metastases; significant recent bleeding; uncontrolled hypertension; and ongoing anti-coagulation. Pregnant or nursing women were not eligible. Results: Twenty-one patients (67% male) were enrolled with a median age of 55 years. Most patients had M1c disease (80%) and 62% had prior chemotherapy for stage IV melanoma. None of the patients were ineligible/canceled participation. After the first stage of the trial was complete, only 3 of the first 20 patients enrolled were progression-free at 18 weeks. Having not met the minimal clinical efficacy requirement (at least 7 of the first 20 patients progression-free at 18 weeks) the trial was closed to further accrual. Correlative laboratory studies suggested decreases in some of the measured parameters of angiogenesis (VEGFC, circulating endothelial cells) with no impact on immune homeostasis. Conclusions: Single agent ABT-510 therapy administered at 100mg twice/day to patients with previously treated metastatic melanoma did not demonstrate significant clinical efficacy. However, changes in measured parameters of angiogenesis suggest possible clinical efficacy with higher dosing or in combination with cytotoxic therapy. [Table: see text]
Bilateral prophylactic mastectomy: Complications and subsequent procedures
Authors: C. N. West, M. B. Barton, A. I. Liu, A. M. Geiger
Journal: Journal of Clinical Oncology (2004)

6041 Background: Bilateral prophylactic mastectomy is highly efficacious but little is known about the complications or subsequent procedures needed to rectify complications or cosmetic problems. We therefore studied the complications and procedures occurring after bilateral prophylactic mastectomy. Methods: We used automated hospitalization and cancer registry records to identify women who underwent bilateral mastectomy without breast cancer at one of six health maintenance organizations between 1979 and 1999. Structured medical record reviews confirmed that bilateral mastectomies were done for prophylactic reasons, identified timing of initial reconstruction and ascertained complications and subsequent procedures. Results: During the study period 270 women underwent bilateral prophylactic mastectomy. Median age of women at surgery was 44 years (range 23 to 74) and the majority (90%) were Caucasian. Most women (179, 66%) had simultaneous reconstruction but 36 (13%) had delayed reconstruction and 55 (20%) had none. After bilateral prophylactic mastectomy 466 complications occurred in 171 (63%) women, with a median of two per woman (range 1 to 13). Over half (55%) required repair, including excessive scarring and implant leakage or rupture. About a third (167, 36%) were temporary, including hematoma, hemorrhage and infection. The remaining 42 (9%) complications were permanent or psychological, including lymphedema and depression. A total of 822 subsequent procedures were performed in 167 (62%) women, with a median of 4 per woman (range 1 to 22). Nearly all (766, 93%) were cosmetic in nature. Complications and subsequent procedures were less common in women with no reconstruction (chi square p=0.067 and p=<0.001 respectively) but occurred in nearly identical proportions among women with simultaneous or delayed reconstruction (chi square p=0.764 and p=0.958 respectively). Conclusions: Women undergoing bilateral prophylactic mastectomy are at risk for a range of complications and after reconstruction additional procedures may be required. Women and their physicians need to weigh these risks with the potential benefits of bilateral prophylactic mastectomy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NCI