tbuckley/cabot-search huggingface dataset:
AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study.
Authors: B A Parker, M Santarelli, M R Green, J R Anderson, M R Cooper, D Case, M Barcos, B A Peterson, A J Gottlieb
Journal: Journal of Clinical Oncology (1993)

PURPOSE In an attempt to improve the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphomas, a phase II evaluation of a regimen consisting of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, Oncovin (vincristine; Eli Lilly Co, Indianapolis, IN), prednisone, leucovorin, cytarabine (ara-c), cyclophosphamide, and etoposide (AMOPLACE) was conducted. This regimen includes three additional agents not found in CHOP, uses weekly doses of alternating myelosuppressive and nonmyelosuppressive drugs, and incorporates most single agents active against diffuse lymphomas. PATIENTS AND METHODS Ninety-one previously untreated patients were enrolled and 60 patients were confirmed eligible after central pathology review. Fifty-eight percent of patients had diffuse large-cell lymphoma (DLCL), 83% had stage III or IV disease, and 45% had B symptoms. RESULTS Patients were treated with six to eight cycles of AMOPLACE and analyzed for response and survival. With a median follow-up of 48 months, complete responses (CRs) were seen in 68% of all patients with failure-free survival (FFS) and overall survival (OS) estimates at 4 years of 45% and 54%. In the DLCL subset, the CR rate was 69% and FFS and OS estimates at 4 years were 49% and 60%, respectively. The major toxicity was myelosuppression, with 73% of patients having WBC nadirs less than 1,000/microL; two treatment-related deaths occurred. CONCLUSION We conclude that AMOPLACE is associated with CR and OS rates comparable with those of other third-generation regimens.
A phase II study of single agent depsipeptide (DEP) in patients (pts) with radioactive iodine (RAI)-refractory, metastatic, thyroid carcinoma: Preliminary toxicity and efficacy experience
Authors: Y. B. Su, R. M. Tuttle, M. Fury, R. Ghossein, B. Singh, K. Herman, E. S. Venkatraman, H. Stambuk, R. Robbins, D. G. Pfister
Journal: Journal of Clinical Oncology (2006)

5554 Background: RAI-refractory thyroid cancer carries a poor prognosis, and no effective systemic therapy exists. DEP is a potent histone deacetylase inhibitor with broad in vitro and phase I anti-tumor activity, and has restored sodium-iodide symporter expression and RAI avidity in thyroid cancer cell lines. Methods: Eligible pts have confirmed papillary, follicular, or Hürthle cell carcinoma, progressive measurable disease, and adequate hepatic/renal function. All pts are RAI-refractory by diagnostic RAI whole body scan (WBS). Prior chemotherapy in the recurrent/metastatic setting, and history of significant cardiac disease are exclusions. DEP 13 mg/m 2 IV is given on day 1, 8, and 15, every 28 days. A novel Simon 2-stage design specifies an initial accrual of 21 pts, with expansion to 41 total pts if 2 RECIST responses or 6 pts with PFS at 6 months are observed. Primary outcome is RECIST response rate. Change in RAI avidity (by diagnostic RAI WBS) is a secondary outcome. Results: To date, 14 pts have been enrolled: female 50%, median age 62 (42–78), median Karnofsky 90 (70–100), papillary/follicular/Hürthle histology (7/1/6). Grade 3–5 toxicities possibly related to drug: grade 5 sudden death (1); no grade 4 toxicity; grade 3 toxicity - fatigue (1), dysphagia (1), dyspnea (1). No grade 3 thrombocytopenia (phase I DLT) has been observed. Grade 1 (6) and grade 2 (4) fatigue have been common. As a result of the grade 5 event, protocol accrual and treatment were suspended temporarily. After NCI-CTEP review, more restrictive cardiac exclusions were added and protocol accrual was resumed. Response at 2 months: stable disease (4); progression (2); inevaluable (6, due to protocol suspension); withdrew consent (1); too early (1). In a proof-of-principle event, clinically significant restoration of RAI avidity was observed in a 78 year-old woman with papillary carcinoma. Per protocol, she was taken off study and given treatment-dose RAI; post-therapy WBS confirmed dramatic RAI avidity. Conclusions: Preliminary signs of in vivo reversal of RAI resistance have been observed. Accrual continues with more restrictive cardiac exclusions, and close surveillance for cardiac events. No significant financial relationships to disclose.
A phase II study of XL184 in patients (pts) with progressive glioblastoma multiforme (GBM) in first or second relapse
Authors: J. F. De Groot, M. Prados, T. Urquhart, S. Robertson, Y. Yaron, A. G. Sorensen, A. Norton, T. Batchelor, J. Drappatz, P. Wen
Journal: Journal of Clinical Oncology (2009)

2047 Background: XL184 is a potent orally bioavailable inhibitor of MET, RET, KIT, and VEGFR2. Elevated levels of VEGFR2 and its ligand VEGF are found in GBM, and elevated levels of MET and KIT are correlated with poor prognosis in GBM pts. Treatment with XL184 results in potent inhibition of GBM in preclinical models. Methods: This is a phase II study of 46 pts with recurrent GBM who received XL184 175mg PO qd. Co-primary objectives are 6-month progression-free survival (PFS6) and safety. Secondary objectives include response rate (per MacDonald Criteria), duration of response, overall survival, pharmacodynamic and pharmacokinetic parameters, vascular imaging, and changes in steroid usage. Results: As of January 6, 2009, all 46 pts have been enrolled. At least 1 post-baseline tumor assessment at 4 weeks was available for 26 pts. Of these, 17 pts had not received prior therapy with an anti-angiogenic agent, whereas 9 pts had received prior therapy with bevacizumab (n = 6), vandetanib (n = 2), or VEGF-TRAP (n = 1). Safety: 6 pts have experienced a total of 9 possibly related grade 3/4 SAEs including increased troponin I and myocarditis (n = 1); dehydration, nausea, and fatigue (n = 1); elevated ALT (n = 1); pulmonary embolism (n = 2); and CNS hemorrhage (n = 1). 24/46 (52%) pts have required a dose interruption or reduction due to AEs or SAEs. Based on investigator assessment of bidimensional contrast-enhancing tumor measurements, 10 pts (38%) had a best radiologic response of &gt;= 50% reduction from baseline (including 1 pt with a 100% reduction), 9 pts (35%) had tumor measurement changes ranging from +24% and -49%, and 7 pts (27%) had a &gt;= 25% increase in tumor burden. Of the 17 anti-angiogenic-naïve pts, 9 (53%) had a best radiologic response of &gt;= 50% reduction in tumor burden. 1 pt with prior vandetanib therapy has experienced a best radiologic response of &gt;= 50%. Of the 4 pts with &gt; 6 months follow-up, 3 remain on study with a sustained radiologic response. Conclusions: XL184 at a dose of 175 mg PO qd, has demonstrated substantial activity in pts with progressive or recurrent GBM. Updated safety and efficacy results including centrally reviewed PFS6 and response rate will be reported. [Table: see text]
Using prostate-specific antigen threshold to identify increased 4-year risk of prostate cancer.
Authors: E. Crawford, S. S. Sutton, J. W. Moul, C. A. Pettaway, J. W. Hardin, S. A. Poston, E. J. Kruep
Journal: Journal of Clinical Oncology (2010)

4565 Background: Recent studies have shown a patient's prostate specific antigen (PSA) value can predict risk of future prostate cancer (PCa) development. In the European Randomized Study of Screening for Prostate Cancer (ERSPC), men with PSA ≥1.5 ng/mL had significantly greater risk of developing PCa within 4 years than men with PSA <1.5 ng/mL (9.2% vs 1.5%, respectively; OR=7.466; P<.001). A recent assessment in a Henry Ford population indicated that, across the lower spectrum of PSA values, PSA of 1.5 ng/mL optimally predicted future risk of PCa. The current analysis aimed to assess the PSA threshold value that optimally predicts future risk of PCa in a cohort of veterans. Methods: This is a retrospective analysis of men in the Veterans Health Administration database from 2000-2009. Men ≥40 years with a baseline PSA ≤4.0 ng/mL, not receiving 5-alpha reductase inhibitors, and without a PCa diagnosis prior to first PSA date were included and followed for 4 years. Patients diagnosed with PCa within 6 months of index were excluded. Optimal PSA threshold value for risk of future PCa development was determined by receiver operator characteristic (ROC) curves. Results: Of 150,293 patients identified for the analysis, 33,217 were classified as Caucasian, 20,680 as African American, 440 as Other Race (subsequently excluded due to a small sample size), and 95,956 patients had race missing. At baseline, mean age was 59.5 years and mean PSA was 1.11 ng/mL. Overall, 4-year rates of PCa were ∼1.3% for Caucasians and African Americans, and 0.97% for unknown race. Mean time to PCa diagnosis was 2.01 years across all patients. ROC curves indicated a 2.3 PSA threshold (area under the curve [AUC] = 73.5%) optimally predicted future PCa in Caucasians, and a 1.9 threshold (AUC = 84.3%) optimally predicted PCa in African Americans; across all patients, a 1.9 PSA threshold was optimal. Conclusions: A relatively low PSA threshold optimally predicted future cancer risk and may identify candidates for risk reduction strategies. Previous studies suggested a cutoff value for PSA >1.5 ng/mL as predictive of future PCa development; our results suggest a PSA threshold of ∼2.0 was most optimal in predicting PCa within 4 years. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
SWOG 0514: A phase II study of sorafenib (BAY 43–9006) as single agent in patients (pts) with unresectable or metastatic gallbladder cancer or cholangiocarcinomas
Authors: A. B. El-Khoueiry, C. Rankin, H. J. Lenz, P. Philip, S. E. Rivkin, C. D. Blanke
Journal: Journal of Clinical Oncology (2007)

4639 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Gemcitabine and fluoropyrimidine- based chemotherapy results in occasional responses and a median survival approaching 6 months. Given the presence of b- raf mutations and overexpression of VEGF in biliary cancers, we initiated a study to evaluate the efficacy of sorafenib, a multitargeted tyrosine kinase inhibitor of c and b-Raf, VEGFR-2/3 and PDGFR, in pts with metastatic biliary cancers. Methods: Pt eligibility included adequate organ function and no prior treatment for metastatic disease. The primary end-point was objective response rate (RR). Secondary endpoints were overall survival (OS) and progression free survival (PFS). A two-stage design was used to detect a difference in the null hypothesis of 5% response probability and the alternative 20% response probability. If at least one confirmed response occurred after the first 25 pts, another 25 were to be accrued. Sorafenib was administered at 400 mg PO BID continuously. A cycle was defined as 28 days of therapy, and radiological assessment was done every 2 cycles. Results: 36 pts were enrolled during the first stage of accrual. 5 pts were ineligible. 52% were female. Median age was 57.8 years (range 33.8–81.5). Adverse events: 1 pt died with grade 4 supraventricular tachycardia and venous thromboembolism. Grade 3/4 toxicities were noted in 20 pts (66.7%) and included hand-foot syndrome in 4 pts (13%), while thrombosis/embolism, elevated liver transaminases, and abdominal pain were each seen in 3 pts (10% for each). Reversible posterior leukoencephalopathy syndrome, GI perforation, and GI hemorrhage were each seen in 1 pt (3% for each). 2 pts (6%) had an unconfirmed partial response and 9 pts (29%) had stable disease. 27 pts have progressed. Median PFS was 2 months (95% CI: 2–4 months). 14 pts have died, with a median survival estimate of 6 months (95% CI: 4–10 months). Conclusions: Sorafenib did not result in a clinically significant objective RR in pts with gallbladder and cholangiocarcinoma but demonstrated an impact on survival that may be comparable to commonly used chemotherapy regimens. No significant financial relationships to disclose.
P2.17 Proteomics and Gene Expression Profiling of Melanoma Chemotherapy Response in Tumors
Authors: C. Hertzman Johansson, A. Azimi, M. Pernemalm, Y. Pawitan, M. Frostvik Stolt, V. Lazar, J. Lundeberg, J. Lehtiö, S. Egyhazi, J. Hansson
Journal: Annals of Oncology (2012)
Use of the combination of raltitrexed (R) and oxaliplatin (O) as a salvage treatment for patients with advanced colorectal cancer (ACRC) refractory to 5-fluorouracil (5-FU) based chemotherapy and with hyperexpression of thymidylate synthase (TS): Final report
Authors: A. M. Murad, R. Guimaraes, A. O. Scalabrini-Neto, N. Ourives
Journal: Journal of Clinical Oncology (2004)

3727 Background: TS is an important target for fluoropyrimidine based TS inhibitors and its hiperexpression has been correlated with resistance to 5-FU, but not necessarily to R, a folate-based TS inhibitor, which appears to be more correlated to FPGS activity (van Triest et al, 1999; Cheradame et al, 1999). O is a novel diaminocyclohexane platinum agent also active in ACRC and obviously not related to TS status. Methods: 21 patients with ACRC not responsive to a first line 5-FU based chemotherapy: 14(67%) to IFL(Saltz) regimen, 4(19%) to 5-FU/LV- (Mayo Clinic) regimen and 3(14%) to capecitabine) and high expression of TS (determined by IHC technique-grades 2+ and 3+) and age less than 70 Y/O, measurable disease, WHO PS 0–2, life expectancy ≥ 2 months, adequate renal and liver functions and informed consent were accrued to receive: T – 3.0 mg/m2 and O – 120mg/m2 every 21 days until progression. Results: Thirteen were male and 8 female; median age: 58(39–67); median PS: 1 (1–2). Number of cycles administered: 98 (median per patient: 4). There were 7 PR (33%), 3 SD(14%) and 11(53%) PD. Clinical benefit based upon weight gain, PSand analgesic consumption was observed in all 7 responders (33%). The median PFS was 6.5 months (1–12) and the median overall SV was 8 months (2–12+). The 1 year SV was 17%. The regimen was well tolerated. WHO grade 4 diarrhea occurred in one patient, grade 3 in 12(12%) cycles; grade 2 vomiting in 10(10%) cycles; grades 3 and 4 neutropenia in 16(16%) cycles; reversible febrile neutropenia in 2 patients: (onedied due to sepsis); grade 3 thrombocitopenia in 6(6%) cycles; anemia grades 2 and 3 in 21(21%) cycles and grade 2 oral mucositis in 3 (3%) of the cycles. Grades 1 and 2 neuropathy was observed in 61% of the cycles. Conclusions: These favorable results suggest that this combination might be effective in the treatment of patients with ACRC with high expression of TS and should be also explored as a first line regimen for this subset of patients with predictable resistance to fluoropyrimidine based chemotherapy. No significant financial relationships to disclose.
Prognostic relevance of epilepsy at presentation in glioblastoma patients
Authors: Sharon Berendsen, Meri Varkila, Jérôme Kroonen, Tatjana Seute, Tom J. Snijders, Frans Kauw, Wim G.M. Spliet, Marie Willems, Christophe Poulet, Marike L. Broekman, Vincent Bours, Pierre A. Robe
Journal: Neuro-Oncology (2015)

Epileptogenic glioblastomas are thought to convey a favorable prognosis, either due to early diagnosis or potential antitumor effects of antiepileptic drugs. We investigated the relationship between survival and epilepsy at presentation, early diagnosis, and antiepileptic drug therapy in glioblastoma patients. Multivariable Cox regression was applied to survival data of 647 consecutive patients diagnosed with de novo glioblastoma between 2005 and 2013 in order to investigate the association between epilepsy and survival in glioblastoma patients. In addition, we quantified the association between survival and valproic acid (VPA) treatment. Epilepsy correlated positively with survival (HR: 0.75 (95% CI: 0.61–0.92), P < .01). This effect is independent of age, sex, performance status, type of surgery, adjuvant therapy, tumor location, and tumor volume, suggesting that this positive correlation cannot be attributed solely to early diagnosis. For patients who presented with epilepsy, the use of the antiepileptic drug VPA did not associate with survival when compared with patients who did not receive VPA treatment. Epilepsy is an independent prognostic factor for longer survival in glioblastoma patients. This prognostic effect is not solely explained by early diagnosis, and survival is not associated with VPA treatment.
Conventional-dose versus high-dose chemotherapy in relapsed or refractory male germ-cell tumors: A retrospective study in 1,594 patients.
Authors: A. Lorch, C. Mollevi, A. Kramar, L. H. Einhorn, A. Necchi, C. Massard, U. DeGiorgi, A. Flechon, K. A. Margolin, J. Beyer
Journal: Journal of Clinical Oncology (2010)

4513 Background: Salvage treatment in male patients (pts) with relapsed or refractory germ-cell tumors (rr-GCT) can be administered using conventional-dose (CDCT) or high-dose (HDCT) chemotherapy. Methods: We retrospectively compared the results of CDCT (n=773) and HDCT (n=821) within five well-defined prognostic categories of 1,594 pts with rr-GCT (Lorch ASCO 2009). All pts received first salvage treatment with modern type cisplatin-based CDCT or carboplatin-based HDCT after January 1, 1990, at 38 expert centers worldwide. We compared the estimated 2-year progression-free (PFS) and 5-year overall survival (OS) between the two treatment groups using the univariate log-rank statistic and the multivariate Cox model. Results: Reliable classification into the five prognostic categories was limited to the 1,435 pts (90%) with non missing values in the relevant disease characteristics. The two treatment groups were similarly distributed within each of the five prognostic categories despite slight differences in age and specific disease characteristics. PFS and OS differed significantly between CDCT and HDCT in all risk groups except for OS in the low-risk group. Conclusions: This analysis of treatment effects within five prognostic groups suggests that there may be a benefit from using HDCT as first salvage treatment in pts with rr-GCT, which is more pronounced for PFS than for OS. PFS OS Risk category Events 2 years HR Deaths 5 years HR All pts (n=1,594) CDCT (773) 572 27.8% 1 423 40.8% 1 HDCT (821) 418 49.6% 0.48* 362 53.2% 0.68* Very low (n=76) CDCT (37) 16 58.4% 1 13 64.5% 1 HDCT (39) 4 91.6% 0.18* 4 88.7% 0.24* Low (n=257) CDCT (122) 78 40.0% 1 40 66.2% 1 HDCT (135) 50 64.3% 0.45** 45 64.5% 1.06** (ns) Intermediate (n=646) CDCT (318) 229 31.9% 1 158 45.5% 1 HDCT (328) 156 53.5% 0.46** 129 58.3% 0.61** High (n=351) CDCT (152) 122 17.2% 1 109 23.0% 1 HDCT (199) 131 33.3% 0.47** 123 35.2% 0.61** Very high (n=105) CDCT (54) 53 1.9% 1 48 3.4% 1 HDCT (51) 39 22.0% 0.36** 33 27.0% 0.44** * Univariate log-rank test. ** Adjusted Cox model. No significant financial relationships to disclose.
Validation of Cytokeratin 19, Mammaglobin A and B in detection of breast cancer cells in the bone marrow using a nested reverse transcriptase polymerase chain reaction (RT-PCR) assay
Authors: F. Janku, J. Novotny, Z. Kleibl, P. Tesarova, L. Petruzelka, B. Matous, M. Safanda, M. Zemanova, P. Mares
Journal: Journal of Clinical Oncology (2004)

9672 Background: Early hematogenous spread of occult tumor cells is a crucial event in tumor progression and formation of distant metastases. Several markers mainly cytokeratins have been validated to date using immunohistochemistry (IHC) or more sensitive reverse transcriptase polymerase chain reaction (RT-PCR). The role of Cytokeratin 19 (CK-19) remains controversial regarding it's sensitivity and specificity. In contrast Mammaglobin was reported as a breast specific marker with very high specificity. In this feasibility study we validated expression of CK19, Mammaglobin A and B in the bone marrow samples of patients with breast cancer. Methods: We obtained bone marrow aspirates of 48 patients with stage I (38%), II (58%) and III (4%) breast cancer who underwent either immediate complete resection of the tumor or neoadjuvant therapy with subsequent curative surgery. mRNA was isolated using QIAamp RNA blood mini kit (Qiagen ®). Subsequently two-step nested RT-PCR for the expression of CK-19, Mammaglobin A and B was performed. Results: CK-19 was detected in all 48 samples. Mammaglobin A was detected in samples from 6 (12,5%) out of 48 patients. Two samples (4%) were positive for Mammaglobin B. Only one patient had both Mammaglobin A and B transcripts in the bone marrow. With a median follow-up of 20 (4–33) month we observed only 2 recurrences, both in patients without occult tumor cells in the bone marrow. Conclusions: CK-19 showed neither diagnostic nor prognostic value as a mRNA marker in the RT-PCR detection of occult tumor cells in the bone marrow. Mammaglobin A may be a useful tool for detection of occult breast cancer cells in the bone marrow but it's clinical and prognostic relevance should be further investigated. Mammaglobin B showed lower sensitivity and should be further validated. Acknowledgement: Supported by a grant IGA MZ CR NC/6672–3 and MSMT CR CEZ: J13/98 1111 0000 4. No significant financial relationships to disclose.
A phase II study of the PARP inhibitor ABT-888 plus temozolomide in patients with heavily pretreated, metastatic colorectal cancer.
Authors: M. J. Pishvaian, R. Slack, A. Witkiewicz, A. R. He, J. J. Hwang, A. Hankin, K. Dorsch-Vogel, D. Kuda, T. McAndrew, L. M. Weiner, J. Marshall, J. R. Brody
Journal: Journal of Clinical Oncology (2011)

3502 Background: Inhibitors of poly(ADP-ribose) polymerase (PARP), such as ABT-888 are potent sensitizing agents for, and have been safely combined with DNA-damaging chemotherapeutic agents such as temozolomide (TMZ). The sensitizing effects of PARP inhibitors are magnified when cancer cells harbor underlying defects in DNA repair mechanisms. Methods: We performed a single arm, open label phase II study. Patients with metastatic, unresectable colorectal cancer (CRC) whose disease had progressed on all standard therapies were eligible. Patients received TMZ (150mg/m2 orally daily) days 1-5, and ABT-888 (40mg orally twice-a-day) days 1-7 of each 28-day cycle. Restaging studies were performed every 8 weeks. The primary endpoint was the disease control rate (DCR), defined as complete response, partial response (PR), or stable disease (after two cycles). This trial followed a Simon’s two-stage optimal design using p0=0.10 and p1=0.25 and type I and II errors of 0.10. Secondary clinical endpoints included response rate (RR) and time to progression (TTP). Archived tumor specimens were used for immunohistochemistry (IHC) to assess mismatch repair enzyme (MMR) and PTEN protein expression. Results: Between 09-2010 and 01-2011, 47 patients received treatment. The median age was 54, and most patients had an ECOG PS of 1. The average number of prior therapies was 4. The combination of ABT-888 plus TMZ was very well tolerated. There were only five grade 3 adverse events, all related to myelosuppression, which resolved with a one week treatment delay. The primary endpoint was successfully met, with a DCR of 23%. There were two confirmed PRs, for a RR of 5%. The median TTP was 11 weeks overall, but was 23 weeks in the patients who had disease control. 45 archived tumor samples were obtained, and the results of IHC for the MMR and PTEN proteins will be reported. Conclusions: In this heavily pretreated CRC patient population, the combination of ABT-888 and TMZ was very well tolerated and exhibited clinical activity. Further molecular analyses of patients’ tumor samples, and enrollment of a 20 patient MMR-deficient expansion cohort may help identify which patient subgroups are most likely to respond to therapy.