tbuckley/cabot-search huggingface dataset:
A phase I/II study of arsenic trioxide, bortezomib, and ascorbic acid in relapsed or refractory multiple myeloma
Authors: J. R. Berenson, J. V. Matous, D. Ferretti, R. A. Swift, R. A. Mapes, B. Morrison, H. S. Yeh
Journal: Journal of Clinical Oncology (2006)

7611 Background: The combination of arsenic trioxide (ATO) and bortezomib (B) has shown synergistic anti-tumor activity against human multiple myeloma (MM) cells in preclinical studies, suggesting that this combination may effectively treat patients with MM. In addition, ascorbic acid (AA) can sensitize MM cells to the cytotoxic effects of ATO. Methods: Patients with relapsed or refractory MM were enrolled in this phase I/II dose-escalation trial in 6 cohorts. Patients were given ATO (0.125 or 0.250 mg/kg), B (0.7, 1.0, or 1.3 mg/m 2 ), and a fixed dose of AA (1000 mg) IV on days 1, 4, 8, and 11 of a 21-day cycle for a maximum of 8 cycles. The planned sample size was a maximum of 27 evaluable patients. The primary endpoint was safety and tolerability of the ATO/B/AA regimen in patients with relapsed or refractory MM. Results: At the time of this interim analysis, 22 patients (median age, 63 years) have been enrolled, and accrual has been completed on all cohorts. This group had failed a median of 4 (range, 3–9) prior therapies. One occurrence of grade 4 thrombocytopenia was observed. One occurrence of asymptomatic arrhythmia led to patient withdrawal. All other adverse events were grade 1 or 2. For the 21 patients evaluable for efficacy, objective responses were observed in 10 patients (43%), including 2 complete (CR), 2 partial (PR), and 5 minor (MR) responses. Only 1 (1 MR) of 6 patients receiving the lowest dose of B (0.7 mg/m 2 ) showed a response, whereas 8 (2 CR, 2 PR, and 4 MR) of 15 patients receiving the higher doses (1.0 or 1.3 mg/m 2 ) responded. Conclusions: The ATO/B/AA regimen was well tolerated by the majority of patients, and produced objective responses in 43% of the patients in this heavily pretreated group. The results of this phase I/II study warrant further clinical evaluation of the ATO/B/AA combination regimen for the treatment of patients with relapsed or refractory MM. [Table: see text]
The Role of Scheduled Ct Follow-Up in Patients with Curatively Resected Colorectal Cancer
Authors: Mina Kato, Hidekazu Yamaura, Yozo Sato, Masataka Kashima, Hiroshi Kawada, Shinichi Murata, Koji Komori, Yoshitaka Inaba
Journal: Annals of Oncology (2014)
In situ bioluminescent imaging of xenograft progression in an orthotopic mouse model of HNSCC
Authors: R. A. Madero-Visbal, I. C. Hernandez, J. N. Myers, C. H. Baker, T. D. Shellenberger
Journal: Journal of Clinical Oncology (2008)

17006 Background: An orthotopic model of human tongue cancer in nude mice offers valuable insight to the biologic behavior of squamous cell carcinoma in vivo. After injection of cultured human cancer cell lines into the dorsal tongue, mice predictably develop xenografts. However, an endophytic pattern of growth in the mouse tongue limits access to monitoring progression of xenografts in situ and relies solely on investigation of harvested specimens ex vivo at an arbitrary time point. Therefore, we sought to investigate xenograft progression in situ at various time points to correlate with ex vivo parameters. We report a novel technique using human cell lines, tagged with firefly luciferase, and bioluminescent imaging to monitor growth, invasion, and metastasis of xenografts in situ. Methods: Assays of in vitro growth of OSC-19 cells were performed at 24, 48, 72, and 96 hours after plating. Athymic nude mice were injected into the dorsal tongue with 2.5 × 105 OSC-19 cells tagged with luciferase. Four days after inoculation, all mice received intraperitoneal injections of D-Luciferin, 333 μg/g body weight, and xylazine/ketamine anesthesia. Animals were then imaged using the Kodak In-Vivo Imaging System to detect bioluminescence emitted from engrafted tumors. Subsequently, mice were imaged weekly with in vivo through Day 54. Body weights were measured every 4 days. All mice were sacrificed and necropsied. Tongue and regional node specimens were embedded in paraffin, serially sectioned at 200 μm, and stained with hematoxylin and eosin. Results: In triplicate experiments xenograft tumors formed in 90% of animals. By in situ imaging, bioluminescence was detected in the majority of animals within four days of inoculation. Bioluminescence was detected in all xenografts histologic analysis. Bioluminescence intensity correlated strongly with histologic tumor areas and volumes. In 20% of animals, secondary foci of bioluminescence set apart from the primary tumor were found to represent lymphatic metastasis. Conclusions: Bioluminescent imaging is a sensitive means of detecting xenografts derived from labeled cell lines. This novel approach analyzes the progression of xenografts in vivo by serially recording bioluminescent intensity and topography of tumors in situ. *Sponsored by ASCO YIA. No significant financial relationships to disclose.
Brachial plexopathy in breast cancer
Authors: S. Terstriep, K. Amrami, R. Spinner, T. Moynihan
Journal: Journal of Clinical Oncology (2006)

10601 Background: Brachial plexopathy is a well-recognized complication of breast cancer, most attributed to late effects of radiation. However, direct involvement of brachial plexus by recurrent breast cancer occurs. Misdiagnoses may lead to inappropriate attribution of the plexopathy to radiation, and therefore inappropriate therapy. Methods: We report fourteen cases of brachial plexopathy secondary to breast cancer diagnosed at the Mayo Clinic-Rochester from 2003 to 2005. Results: Thirteen of fourteen primary tumors and 12/14 recurrences were ER/PR positive. Only 1/14 patient had Her 2 neu overexpression. The median time from the original breast cancer diagnosis to first brachial plexus symptom was 14 years. The median time from the development of symptoms to diagnosis was 8 months with the range being 1 month to 8 years. MRI revealed a distinct mass in 3/13 patients, plexus thickening in 5/13, and was normal in 5/13. Only 5/13 original MRI interpretations suggested tumor. In four patients that the 1.5 T MRI was either interpreted as normal or unlikely cancer the 3 Tesla MRI revealed abnormal uptake suggestive of malignancy. PET scan suggested malignancy in 3/6 patients. Two of these cases had other metastatic disease. In the other three cases that PET scans were done the uptake was mild, suggesting inflammation rather than malignancy. Reinterpretations of the PET scan and MRI in combination by an experienced musculoskeletal radiologist was highly suggestive of malignancy in all cases. Definitive diagnosis was eventually obtained by biopsy of the brachial plexus (7/14) or another site of metastasis in (4/14). Conclusions: The often slowly progressive nature of hormonally driven breast cancer can mimic radiation induced brachial plexopathy. In the cases reviewed, PET was not reliable in differentiating inflammation from tumor. MRI findings are nonspecific and higher resolution 3T MRI may be needed to detect an abnormality. Interpretation of MRI and PET together is useful. Patients with a history of breast cancer, and brachial plexus symptoms should be carefully evaluated with consideration for recurrent disease as a cause. Biopsy of the brachial plexus can be done safely and has an important role in diagnosis. No significant financial relationships to disclose.
Tamoxifen discontinuance among women aged 65 years and older with estrogen receptor positive breast cancer
Authors: C. Owusu, D. Buist, T. Field, T. L. Lash, S. Thwin, R. Silliman
Journal: Journal of Clinical Oncology (2006)

648 Background: Five years ofadjuvant tamoxifen therapy in estrogen receptor (ER)-positive breast cancer is more effective than two years of use. However information on adjuvant tamoxifen therapy discontinuance is scanty. We aimed to identify predictors of tamoxifen discontinuance in older women with early stage breast cancer. Methods: Within six healthcare delivery systems, we identified 1080 women ≥65 years with stage I-IIb breast cancer diagnosed from 1990 to 1994 with ER-positive or indeterminate tumors who had been prescribed tamoxifen. We then followed them for five years post initial tamoxifen prescription. Data sources included tumor registries, administrative data, and medical records. We used automated pharmacy records to validate tamoxifen prescription information collected from medical records. The primary endpoint was tamoxifen discontinuance, operationalized as ever discontinuing tamoxifen during follow-up. We excluded women who discontinued tamoxifen due to recurrence, death or disenrollment from this definition. Independent variables included demographic characteristics, comorbidity, tumor characteristics, and primary therapy. We used Cox proportional hazards to determine predictors of tamoxifen discontinuance. Results: Of the 1080 women who were prescribed tamoxifen, 974 women did not have a recurrence, die or disenroll during follow-up. Of these 974 women, 489 (50%) stopped taking tamoxifen during the five years of follow-up. Discontinuers were more likely to be women aged 80 years and older (versus aged 65–69, hazard ratio (HR)= 1.96, 95% confidence interval (CI)=1.51–2.56); have a Charlson Comorbidity Index of 1 (versus a Charlson Comorbidity Index of 0, HR=1.31, CI=1.07–1.61); have indeterminate receptor status (versus ER-positive, HR=1.49, CI=1.12–2.00); and to have not received breast-conserving surgery with radiation therapy or mastectomy (HR=1.37, CI=1.10–1.71). Conclusion: Attention to non-adherence among women at risk of discontinuance, particularly not receiving guideline care, might improve breast cancer outcomes for these women. No significant financial relationships to disclose.
Temozolomide (TMZ) and radiation (XRT) for brain metastasis of solid tumors
Authors: R. Addeo, L. Montella, R. Guarrasi, A. Dello Russo, V. Faiola, S. Del Prete
Journal: Journal of Clinical Oncology (2006)

1543 Background: Whole Brain Radiotherapy (WBRT) remains the mainstay of therapy for brain metastasis of solid tumours not amenable to surgical resection. Temozolomide (TMZ) is a new orally administered imidazo-tetrazine with a mechanism of action and efficacy similar to dacarbazine (DTIC). It has been already used alone or in combination with radiotherapy in the treatment of primary brain tumours is currently used in the therapy of malignant glioblastomas also as single agent. Methods: Patients with solid cancers and recurrent or progressive brain metastases (BM) were eligible. We have treated 59 consecutive patients (32 F and 27 M, mean age: 56.2 ± 23.8 yrs; median age: 58.5 yrs) affected by brain metastases from different solid tumours (21 breast adenocarcinoma, 22 non small lung cancer, 16 other primitive cancers type) with WBRT at 3 Gy/day administered over a two-week period (on wks 1–2), total dose 30 Gy, and an induction with TMZ 75 mg/m 2 /day during this period, following TMZ 750mg/m 2 fractionated in 5 days every 28 days, for up to 6 cycles. Pts who received at least one cycle of TMZ were assessable for response. Results: All patients were subjected to the induction therapy and 154 cycles were performed, mean cycles 3,7. Fifteen grade II and ten grade I neutropenia (CTC), 2 grade II hand and foot syndrome, seven grade I and four grade II thrombocytopenia and nine grade I alopecia were recorded. Fourteen grade I nausea and vomiting were observed, moreover, liver or renal toxicity were never recorded in our series being the schedule well tolerated in all patients. Five CR, in patients with breast cancer and NSCLC, and 21 PRs were recorded in 11 patients with breast tumours, 9 patients with NSCLC and 3 in other cancers, while a clinical benefit was achieved in other 18 patients. Seventeen still alive pts. (breast, NSCLC and colorectal cancer respectively), who achieved a PR and a SD, had an OS between 17 and 8 months, respectively. At the present, in our series, overall survival was 59% at 1 year. Patients continue to be followed to evaluate long term effects of the treatment. Conclusions: The schedule was safe and well tolerated (also in old pts.) and has suggested an encouraging activity in brain metastases from breast and lung cancer. No significant financial relationships to disclose.
A phase I/II trial of clofarabine in patients with relapsed T-cell or NK-cell lymphomas.
Authors: D. A. Mulford, B. L. Pohlman, P. A. Hamlin, F. Young, E. Pamer, S. M. Horwitz
Journal: Journal of Clinical Oncology (2010)

8046 Background: Peripheral T-cell lymphomas (PTCL) are a heterogeneous and poor prognostic subset of non-Hodgkin's lymphoma. Clofarabine is a nucleoside analog which blocks DNA synthesis via inhibition of ribonucleotide reductase and DNA polymerases, and induces apoptosis. In early phase trials, complete responses (CR) were seen among patients with T/NK-cell lymphomas treated with clofarabine. Methods: In 2006, we began a phase I/II trial to examine the use of clofarabine in patients with relapsed and refractory T or NK lymphomas. The objective of the phase I portion was to identify the maximum tolerated dose (MTD) and determine its toxicities. The phase I portion started at a dose of 4 mg/m2 iv for 3 consecutive days every 3 weeks. The cohort was expanded at the MTD. Results: 29 patients (median age was 54; range, 23-82) have been enrolled. The trial will be closed to accrual in 2 months. The most common histologies include: PTCL-NOS (n=8), transformed mycosis fungoides (tMF) (n=5), ALK- anaplastic large cell lymphoma (n=4), angioimmunoblastic T-cell lymphoma (AITL) (n=4), HTLV-I associated lymphoma (n=4) and NK-lymphoma (n=3). Patients received a median of 3 (range, 1-12) prior chemotherapy regimens. Eleven patients had refractory disease and 12 had received pralatrexate. Pleural effusion (n=1) and prolonged thrombocytopenia (n=1) were seen at the 28 mg/m2 dose level. The 20 mg/m2 dose was then determined to be the MTD. 17% (5/29) of all patients and 21% (5/24) of evaluable patients responded. 2 pts had a CR and 3 had a PR. 7 pts had stable disease and 12 patients progressed. Two out of 4 pts with AITL had a CR. Responses were also seen in pts with NK lymphoma, PTCL, and tMF. Tumor reduction was observed at the following dose levels (mg/m2): 8, 13.2 and 20. Conclusions: Clofarabine can be administered to relapsed and refractory patients with T or NK-lymphoma at a dose of 20 mg/m2 using the schedule outlined above. Responses were seen in 17% of this heavily pretreated group. Clofarabine is tolerable in this patient population and produces responses in a group of patients with few options. No significant financial relationships to disclose.
Flow Cytometric Diagnosis of the Cell Lineage and Developmental Stage of Acute Lymphoblastic Leukemia by Novel Monoclonal Antibodies Specific to Human Pre–B-Cell Receptor
Authors: Keiko Tsuganezawa, Nobutaka Kiyokawa, Yoshinobu Matsuo, Fujiko Kitamura, Noriko Toyama-Sorimachi, Keisuke Kuida, Junichiro Fujimoto, Hajime Karasuyama
Journal: Blood (1998)
Molecular markers in extragonadal germ cell tumors (EGCTs): A matched-case control study
Authors: M. Nikolaou, C. Valavanis, I. Lekka, G. Aravantinos, G. Fountzilas, D. Skarlos, H. Kalofonos, V. Kostopoulou, P. Arapantoni Dadioti, D. Pectasides
Journal: Journal of Clinical Oncology (2005)

9700 Background: The role of markers that regulate apoptosis (p53, bcl-2, bax), proliferation (MIB-1) and cell growth (c-kit, cyclooxygenase-2), has been controversial in germ cell tumors. Methods: 18 archival paraffin blocks from EGCT patients (10 retroperitoneal, 5 mediastinal, 2 pineal, 1 ventricular) and 36 out of 157 available paraffin blocks from testicular cancer patients, matched for age and histology, were included in the study. Immunohistochemical staining for p53, bcl-2, bax, MIB-1, c-kit and cox-2, was performed and the percentage of positive cells was calculated. Conditional logistic multivariate analysis was used to test whether the expression of the above markers differ between extragonadal and testicular germ cell tumors. One way ANOVA and t-test were used to detect the correlations between p53, MIB-1 and the clinical characteristics of the entire population. Results: Overall, 21 seminomas and 33 non-seminomas were identified. All specimens revealed a negative expression for bcl-2 and an aberrant positive expression for the proapoptotic protein bax. Almost all seminomas expressed positive staining for c-kit. Higher mean p53 values were correlated with poorer risk group (11.77 for good risk, vs 23.05 for intermediate and poor risk patients, p=0.04) and with non-seminomatous histology (9.86 for seminomas vs 19.88 for non-seminomas, p=0.038). Mean p53 values were also higher in the chemoresistant group of patients (21.67 vs 14.72), but this difference failed to prove statistical significance (p=0.28). Higher mean MIB-1 values were correlated with poor prognostic risk group (33.03 for good risk, vs 31.66 for intermediate risk, vs 50.77 for poor risk patients, p=0.054). Conditional logistic multivariate analysis revealed that p53, MIB-1 and cox-2 differ significantly between extragonadal and testicular germ cell tumors (odd ratio:1.24, 95% CI:1.0028–1.5376, p=0.047 for p53, odd ratio:1.08, 95% CI:1.0012–1.1743, p=0.047 for MIB-1, odd ratio:-0.89, 95% CI:0.8091–1.0011, p=0.052 for cox-2). Conclusions: P53 overexpression is associated with an aggressive phenotype in germ cell tumors and along with MIB-1 and Cox-2 can be used as adjunct markers to identify the origin of a germ cell tumor. No significant financial relationships to disclose.
A randomized controlled trial (RCT) comparing best supportive care (BSC), 5-FU plus folinic acid (FUFA) and, gemcitabine plus oxaliplatin (Gem-Ox) in management of unresectable gallbladder cancer (GBC)
Authors: A. D. Dwary, A. Sharma, B. K. Mohanti, S. Pal, P. Garg, V. Raina, N. K. Shukla, S. V. Deo, S. Thulkar, V. Sreenivas
Journal: Journal of Clinical Oncology (2009)

4521 Background: GBC is common in females residing in the northern part of India. Surgery is the only curative treatment. Unfortunately most patients present in advance and unresectable stage (median survival 3–4 months). Chemotherapy regimens for GBC are not yet standardized. Studies are few and mostly retrospective with small sample size and usually combine heterogeneous malignancies. Adequately powered RCT are not available. This was rationale to undertake study. Methods: It was single center, open label, three armed RCT. Ethical clearance was taken. Planned sample size was 81 to have type I &amp; type II error probabilities of 0.05 &amp; 0.2 respectively. Primary end point was to compare OS in unresectable GBC between BSC vs. FUFA vs. Gem-Ox arms. Secondary end points were to compare PFS in three arms and toxicity analysis of chemotherapy arms. Inclusion criteria were: proven unresectable GBC, performance state ≤2, adequate bone marrow reserve and normal biochemical profile (bilirubin≤3 mg % &amp; liver enzymes within 5 times of upper limit). Patients in BSC group received symptomatic treatment without anticancer therapy. In FUFA group, weekly bolus doses of 5-FU (425mg/m2) plus Folinic acid (20 mg/m2) were given for a maximum of 30 weeks. In Gem-Ox group patients received gemcitabine (900 mg/m2) plus oxaliplatin (80 mg/m2) days 1 and 8 q3 weekly till maximum of 6 cycles. Results: Eighty one patients were randomized (BSC=27, FUFA=28, Gem-Ox=26). Median OS in BSC, FUFA and gem- Ox arms was 4.5 (CI 0.2–8.8), 5.3 (CI 3–6.2) and 9.3 (CI 5–14) months respectively (p= 0.039)). Median PFS was 2.8 (CI 1.8–3.8), 3.5 (CI 3.2–3.8) and 8.5 (CI 5.7–11.3) months in BSC, FUFA and Gem-Ox arm respectively (p= 0.0001). Chemotherapy arms were generally well tolerated. There was no difference in grade 3/4 toxicities in FUFA and Gem-Ox arm except for deranged liver function test, which was more in Gem-Ox arm (p=0.04). There was no toxic death. Conclusions: Probably this is the first RCT confirming efficacy of chemotherapy (Gem-Ox) compared to BSC in improving OS and PFS in unresectable GBC. Both chemotherapy arms were well tolerated. No significant financial relationships to disclose.
Targeting PIK3CA mutant breast cancer with the combination of PIK3CA-specific inhibitor, BYL719, and IGF1-R antibody, ganitumab.
Authors: Z, Alexander Cao, Maria Pinzon-Ortiz, Yan Chen, Xiaoyan Li, Pedro J. Beltran, Jennifer L. Gansert, Malte Peters, Robert Schlegel, Karl Maria Schumacher, Alan Huang
Journal: Journal of Clinical Oncology (2013)

e13525 Background: PI3K/AKT signaling is a critical growth and survival pathway in many human cancers. PI3Ks are lipid kinases that are important in controlling signaling pathways involved in cell proliferation, motility, cell death and cell invasion. The α isoform of PI3K (PIK3CA) is linked upstream mainly to receptor tyrosine kinases and is commonly mutated in various solid tumor types. The existing scientific evidence strongly supports the concept of targeting PIK3CA in human cancers, especially those harboring PIK3CA mutations. Sustained PIK3CA inhibition may lead to aberrant RTK signaling to attenuate PIK3CA inhibition. IGF1R is a RTK commonly expressed in human neoplasia. Its signaling has been implicated in tumor cell survival. Additionally, IGF1R/IRS signaling has been shown to be a feedback pathway to down-modulate mTOR inhibition by RAD001 in cancer cells. We reason that the efficacy of PIK3CA inhibition would be enhanced if PIK3CA inhibitor is combined with a targeted agent against a key RTK in pAKT signaling. Methods: We set out to examine whether PIK3CA inhibition would also trigger IGF1-R/IRS signaling. In addition, we explored the combination of PIK3CA-specific inhibitor, BYL719, and a fully human antibody against IGF1-R, ganitumab, preclinically against a PIK3CA mutant breast cancer model, MCF7. Results: Our data indicate that IGF1-R/IRS signaling is activated upon PIK3CA inhibition. BYL719 exhibited concentration-dependent tumor growth inhibition in vitro. Ganitumab alone had modest inhibitory activity. The combination of BYL719 and ganitumab inhibited MCF7 growth synergistically in vitro. This combination was further tested in an MCF7 xenograft in mice. BYL719 monotherapy resulted in tumor stasis. Ganitumab alone had marginal growth inhibition. The combination of BYL719 and ganitumab led to tumor regression. Conclusions: Our data suggest that the combination of BYL719 and ganitumab would act synergistically to inhibit PIK3CA mutant breast cancer cells by blocking two inter-connected pathways. The combination of BYL719 and ganitumab has now entered into clinical trial (NCT01708161). It represents a promising approach against PI3KCA mutant breast cancers.