tbuckley/cabot-search huggingface dataset:
Association between exposure to bevacizumab (BV) beyond first progression (BBP) and overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Results from a large observational study (BRiTE)
Authors: A. Grothey, M. Sugrue, E. Hedrick, D. Purdie, J. Yi, W. Dong, M. Kozloff
Journal: Journal of Clinical Oncology (2007)

4036 Background: While BV prolongs OS when used with standard 1 st - or 2 nd -line chemotherapy (CT) in mCRC, no data exist on the effects of BBP. A previous report from BRiTE showed favorable median OS (27.1 mo, 95% CI 24.8-NE), with 1 st line PFS (median 10.1 mo, 95% CI:9.7–10.4) comparable to historical mCRC trials, suggesting significant impact of post-progression survival on OS. This exploratory analysis evaluates the association of various pre- and post-treatment variables with OS in BRiTE. Methods: Pt population and methods have been described previously (Kozloff, ASCO 2006). All pts in BRiTE received BV as part of 1 st -line therapy. The use of BBP and choice of CT were at investigator’s discretion. Kaplan-Meier methods were used to estimate PFS and OS. Cox’s proportional hazard model was used to assess the independent effects of pre- and post-treatment pt- related factors on OS, including age, ECOG PS, albumin, alkaline phosphatase, site of primary tumor, 1 st -line CT regimen, 1 st -line PFS, exposure to all 3 active CT agents, receipt of any 2 nd -line CT, exposure to cetuximab, and BBP. Though there was variability observed in patterns of BBP, including continuous and discontinuous use, for the purpose of this analysis, BBP was defined as any exposure to BV after 1 st progression (PD). Results: A total of 1,953 pts were treated in BRiTE. At median follow-up of 17.5 mo, there were 1,369 1 st PD and 839 deaths. Among pts with 1 st PD, 65.2% received any 2nd-line CT, 34.8% received cetuximab, and 53.8% received BBP. In a multivariate analysis, BBP and exposure to any 2 nd -line CT were independently associated with increased OS (both p&lt;0.0001). Age ≥65, PS ≥1, low albumin, elevated alkaline phosphatase, colon primary, and use of IFL were associated with inferior OS. Conclusions: BBP appears to be associated with longer OS in BRiTE. This finding supports the evaluation of BBP in prospective randomized clinical trials. Other factors that may have impacted this finding, including physician-related variables, will be investigated in future analyses. [Table: see text]
Phase I and pharmacokinetic study of vinflunine (VFL) in combination with carboplatin (CBDCA) for treatment of advanced non-small cell lung cancer (NSCLC) in chemonaive patients (pts): Final results
Authors: J.-M. Tourani, M.-C. Pinel, D. Planchard, V. Aslanis, S. Gouva, G. Robinet
Journal: Journal of Clinical Oncology (2005)

7271 Background: VFL (Javlor) is a novel fluorinated semi-synthetic vinca-alkaloid. The combination of VFL and cisplatin has shown significant antitumour activity in advanced NSCLC (ASCO 2004, abstract 7110). Methods: This trial was designed to determine the recommended dose (RD) of the combination in pts with advanced NSCLC. Were defined as dose limiting toxicity any of the following adverse event occurring during the cycle 1: neutrophils < 0,5 x 109/L for ≥ 7 days or < 0,1 x 109/L for ≥ 3 days; platelets < 25 x 109/L or thrombocytopenia with bleeding or requiring platelet transfusion; febrile neutropenia or any grade (G) 3 or 4 major organ toxicity according to the NCI-CTC scale; withdrawal of any patient after the 1st cycle due to delayed recovery from toxicity. Pharmacokinetic blood sampling was performed to investigate potential drug-drug interaction. Results: Three dose-levels of the combination were investigated in 21 pts; 20 pts are evaluable so far (19 males); WHO performance status 0: 9 pts, 1: 11 pts, median age: 57.9 years (range 46.6–79.8). Patients were presenting with stage IIB (1 pt), IIIA (2 pts), IIIB (1 pt) or IV (15 pts) NSCLC (initial stage unknown in 1 pt). The first 6 patients received VFL 280 mg/m2 and CBDCA AUC 5: one of them experienced G3 constipation.In the second dose level, vinflunine 320 mg/m2/CBDCA AUC 5, 2 pts out of 6 experienced DLT: 1 had febrile neutropenia and the other experienced G4 fatigue together with G3 constipation. The maximum tolerated dose was established in the third dose level explored in 3 pts treated with VFL 320 mg/m2 and CBDCA AUC 6: 1 pt had febrile neutropenia and 1 pt G3 abdominal pain. Preliminary pharmacokinetic analysis did not detect any drug-drug interaction when the two drugs are combined. Conclusions: The RD of the combination is established at vinflunine 320 mg/m2 in combination with CBDCA AUC 5. According to the protocol 6 additional pts were required to confirm this RD and are under analysis. The combination of VFL 320 mg/m2 and CBDCA AUC 5 is safe in pts with previously untreated NSCLC; final results including the antitumour activity of the combination will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pierre Fabre
A retrospective review of adenosquamous carcinoma of the uterine cervix
Authors: Y. Kawakami, K. Takehara, M. Kumagai, M. Hanaoka, Y. Akimoto, T. Mizunoe, F. Saji
Journal: Journal of Clinical Oncology (2007)

16049 Background: Adenosquamous carcinoma (ASC) of the uterine cervix is a rare mixture of malignant squamous and glandular epithelial elements. Clinical analyses of this disease were hardly performed independently from those of adenocarcinoma (AC) of the uterine cervix since both of the patients with these diseases show poorer outcome, compared with those with squamous cell carcinoma, which is present in the majority of cervical cancer. In this study, we investigated clinical features including diagnosis and treatment of this disease. Methods: During 1980–2006, total of 270 patients, who were diagnosed as carcinoma of the uterine cervix, were included in our analysis. A retrospective review of patients with ASC were preformed in their age, stage, lymph node metastasis, tumor markers (SCC, CEA, CA125 and CA19–9), treatment, relapse rate and its location, and survival. Results: There were total of 17 and 34 patients, who were histologically confirmed as having ASC (6.3%) and AC (12.6%) of the uterine cervix, respectively. All the ASC patients underwent surgery. The average age of the patients was 45.0 (26–78). The distribution of illness stages among the patients were IA, 4; IB, 8; IIA, 2; IIB, 2; IIIB, 1. Lymph node metastasis was seen in two patients (11.8%). There were no significant difference in these indexes between ASC and AC. Elevation of serum CA125 was observed in two ASC patients but no AC patients. The recurrence rates were 17.6% and 14.7% in ASC and AC, respectively. Five-year survival were 77.8% in ASC and 78.0% in AC, whereas 92.2% in SCC. Conclusions: These analyses indicate that clinical behavior and its outcome of ASC is similar to those of AC. The treatment based on these clinical features may be a useful to improve the prognosis of this disease. No significant financial relationships to disclose.
Is minimal residual disease in the peripheral-blood stem-cell transplantation of chronic myelogenous leukemia important?
Authors: E C Besa
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.9.3166 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9294481 Is minimal residual disease in the peripheral-blood stem-cell transplantation of chronic myelogenous leukemia important? E C BesaxE C BesaSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.9.3166 PDF "Is minimal residual disease in the peripheral-blood stem-cell transplantation of chronic myelogenous leukemia important?." Journal of Clinical Oncology, 15(9), pp. 3166–3167© 1997 by American Society of Clinical Oncology
Cardiac safety of nonpegylated liposomal doxorubicin in patients with advanced breast cancer treated with myocet plus vinorelbine or myocet plus cyclophosphamide in a randomized phase II trial.
Authors: V. Lorusso, G. A. De Giorgi, M. Ciccarese, V. E. Chiuri, F. Giotta, R. Bordonaro, E. Maiello, S. Pisconti, S. Cinieri, G. Colucci
Journal: Journal of Clinical Oncology (2010)

1119 Background: Treatment with nonpegylated liposomal doxorubicin (Myocet, M) has already shown a reduced level of cardiotoxicity as compared to traditional doxorubicin. We are reporting the cardiac safety of M evaluated in a multicenter randomized phase II trial comparing M plus vinorelbine (V) versus M plus cyclophosphamide (C). Methods: Patients must have LABC or MBC, PS (ECOG≤ 2) and measurable disease. Previous anthracyclines as adjuvant, or endocrine therapy for advanced disease were allowed. They received M 60 mg/m2 plus C 600 mg/m2 iv on day1 of a 21 day cycle (arm A), or M 50 mg/m2 plus V 25 mg/m2 iv on day 1 and V 60 mg/m2 orally on day 8 of a 21 day cycle. Primary objective was ORR, secondary endpoint was safety. Cardiotoxicity was monitored by echocardiogram, performed every 3 cycles for the first 6 cycles and every other cycle afterwords. Results: Between July 2006 and November 2009 178 women were enrolled, 137 are actually evaluable for efficacy and safety (41 pts too early). Patient characteristics: arm A 88 pts, median age 59 (range 37-70), ER status ±/unk 70/26/4%, Her-2 status ±/unk 8/81/11%, PS 0/1/2 70/25/5%, prior anthracyclines 22 pts (25%), visceral site of disease 59 pts (67%). Arm B 90 pts, median age 56 (range 25-70), ER status ±/unk 73/23/4%, Her-2 status ±/unk 9/81/10%, PS 0/1/2 60/34/6%, prior anthracyclines 31 pts (34%), visceral site of disease 58 pts (64%). Median PFS was 55 (95% CI, 35-70) and 39 (95% CI, 25-57) weeks respectively for arm A and arm B. Overall response rate was 49% and 51% for arm A and B respectively. With regard to toxicity, MV showed a slight increase of haematological and non hematological toxicity. Cardiotoxicity as asymptomatic decrease of LVEF of >10% under basal evaluation, was observed in one patient in arm A after 8 cycles, and in 2 pts of Arm B, one of whom was pretreated with anthracyclines. No discontinuation due to adverse events neither treatment-related death was seen in both arms. Conclusions: The combination of M plus C or V is a good alternative for patients with advanced breast cancer, devoid of cardiac toxicity also in pts pretreated with antracyclines as adjuvant. No significant financial relationships to disclose.
Vinorelbine (VRB) plus gemcitabine (GEM) as first-line treatment for elderly patients (p) with advanced non-small cell lung cancer (NSCLC): Molecular correlates
Authors: I. Maestu, D. Isla, P. Diz, J. Muñoz, J. Oramas, R. Garcia, S. del Barco, M. Provencio, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2007)

18040 Background: The clinical benefit of non-cisplatin doublets vs a single agent in elderly or unfit p is still controversial. The present study focuses on clinical outcome with VRB/GEM in elderly p and the role of functional status and comorbidities. Genetic predictive markers of response to VRB/GEM will also be examined in genomic and cDNA from tumor and circulating tumor DNA. Methods: 145 chemonaive p with stage IIIB (pleural effusion or supraclavicular lymph nodes)-IV or recurrent NSCLC and age &gt; 70 years were accrued at 32 sites between April 2004 and January 2006. Treatment consisted of VRB 25 mg/m 2 IV or 60–80 mg/m 2 oral plus GEM 1200 mg/m 2 , days 1, 8 every 21 days. Activities of daily living (ADL), instrumental activities of daily living (IADL) and comorbidities were evaluated. DNA samples were collected from primary tumors for the assessment of microtubule associated protein 4 (MAP4) and from serum for the checkpoint with forkhead-associated and ring finger (CHFR) methylation. Results: Data on 130 p is available. Median age 76 years (69–83); males: 86.8%; smokers: 70.5%; PS 0–1: 83.9%; adenocarcinoma: 34.4% / squamous: 48%; stage IIIB: 22.7%, IV: 77.3%. Self-sufficiency in ADL and IADL was 77.4% and 45.2% of the p analyzed. 68% of the p had comorbidities. Median cycles: 3 (1–8). Hematological toxicities (%p): grade 3/4 neutropenia, 7.8%/4.7%; grade 3/4 thrombocytopenia, 2.3%/0.8%; grade 3 anemia, 3.1%. Efficacy in evaluable population: PR, 23.2% (95% CI, 15.1% to 32.9%); SD, 41.1%. 24 p died during the treatment period (non toxicity related) and 21 p were not evaluable. With a median follow up of 5.8 months, median survival for the whole population was 4.97 months (m), progression free survival 4.53 m, event free survival 3.43 m, 1-year survival 26.6%. Statistically significant differences in median survival were observed among subgroups: PS 0–1/2, 6.5/2.3 m (p&lt;0.001); sex male/female, 4.5/9.7 m (p 0.027); ADL &lt;6/=6, 3.4/7.1 m (p 0.023). Conclusions: This trial confirms that VRB/GEM is effective, presenting a favorable toxicity profile in elderly p with advanced NSCLC. Complete data on genetic markers will be presented. No significant financial relationships to disclose.
Tumor suppressor gene CpG site methylation and outcome in surgically treated stage I-II non-small cell lung cancer patients
Authors: L. Buckingham, L. P. Faber, A. W. Kim, K. Kaiser, C. Barger, S. Basu, M. J. Liptay, P. D. Bonomi, J. S. Coon
Journal: Journal of Clinical Oncology (2008)

11035 Background: Five year survival in completely resected non small cell lung cancer (NSCLC) stage I-II patients approximates 60%. Presently, no adequate prognostic indicators accurately predict outcome. To explore epigenetic influences, promoter methylation (silencing) at multiple CpG dinucleotides of tumor suppressor genes with roles in metastasis and survival was analyzed. Methods: Methylation was quantified at specific CpG sites in p16, MGMT, DAPK, RASSF1, ECAD, LET7–3-a, NORE1(RASSF5) and PTEN promoters in assessable tumor tissue from 88 surgically treated NSCLC patients by pyrosequencing. Results: Overall average promoter methylation ranged from 9.27+6.04% (DAPK) to 71.3+10.5% (LET7–3-a). Of the genes analyzed, RASSF1 showed significant association between overall average promoter methylation and increased recurrence (p=0.024). Upon comparison of methylation at specific CpG sites and any recurrence, MGMT methylation at CpG position 17 in exon1 and DAPK methylation at CpG site -1503 (A of the first ATG codon = +1) were significantly associated with higher recurrence (p=0.030, p=0.031, respectively). NORE1 methylation at -224 and -244 were significantly associated with no recurrence (p=0.024, p=0.030, respectively). Kaplan-Meier survival analysis revealed significantly lower time to regression [TTR; 9.80 vs. 55.2 months (mo), Log Rank p=0.003] and overall survival (OS, p=0.001) with MGMT methylated at exon 1 position 17. Significantly lower TTR and OS were also observed with MGMT methylated at exon 1 position 24 (p=0.020, p=0.017, respectively). In contrast, methylation at -224 in the NORE1 promoter was associated with longer median TTR (p=0.053). Conclusions: These data support an influence of specific CpG site methylation and outcome after surgical resection for stage I and II NSCLC. Methylation was generally associated with shorter TTR and OS, however methylation of particular NORE1 sites was associated with better outcome in this patient group. The effects of methylation of specific promoter sites may reflect accessibility to methylases and/or an interaction of transcription factors required for control of expression of these genes, phenotypically impacting metastatic potential and recurrence. No significant financial relationships to disclose.
13-cis-Retinoic acid does not increase the true remission rate and the duration of true remission (induced by cytotoxic chemotherapy) in patients with chronic phase chronic myelogenous leukemia.
Authors: Z A Arlin, R Mertelsmann, E Berman, T Gee, E Kurland, R S Chaganti, S C Jhanwar, M A Moore, B D Clarkson
Journal: Journal of Clinical Oncology (1985)

Treatment of chronic phase chronic myelogenous leukemia with hydroxyurea or busulfan rarely induces cytogenetic (true) remissions. Intensive chemotherapy induces brief true remissions in approximately 50% of patients. We added 13-cis-retinoic acid to daunorubicin, cytosine arabinoside, and thioguanine to determine if it could increase the incidence and duration of remission induced by cytotoxic chemotherapy. Of the 17 evaluable patients, one patient (6%) achieved complete remission, and seven patients (41%) achieved partial remissions. The median duration of remission was 1.6 months. We conclude that 13-cis-retinoic acid does not increase the incidence and duration of remission in chronic phase chronic myelogenous leukemia.
Cediranib (AZD2171) is an active agent in recurrent epithelial ovarian cancer
Authors: U. A. Matulonis, S. T. Berlin, C. N. Krasner, K. Tyburski, J. Lee, M. Roche, S. P. Ivy, C. Lenahan, M. King, R. T. Penson
Journal: Journal of Clinical Oncology (2008)

5501 Background: Angiogenesis is important for ovarian cancer growth; blocking angiogenesis can lead to ovarian cancer regression. Cediranib (AZD2171) is a highly selective and potent oral tyrosine kinase inhibitor (TKI) of VEGFR1, VEGFR2, VEGFR3, and c-Kit. Methods: CTEP-sponsored phase II study of single agent Cediranib for recurrent ovarian, peritoneal, or tubal cancer. Eligibility: up to 2 prior lines of chemotherapy for recurrence, ECOG PS of 0 or 1, and normal organ function. Primary endpoint is response rate measured either by RECIST or modified GCIG CA125 criteria; other endpoints are PFS, toxicity, and pharmacodynamic endpoints. Results: 29 patients (pts) have been enrolled thus far; 27 are evaluable. 1 pt never started. 24 pts have ovarian cancer; 5 with peritoneal cancer. Of the 28 pts receiving drug, 12 pts had plat-sensitive and 16 had plat-resistant cancer. Starting phase II dose was 45 mg PO, but because of toxicities seen in the first 11 pts, the dose was lowered to 30 mg for subsequent pts. Thus far, grade 3 toxicities include: HTN (n=13; 5 pts on 45 mg and 8 pts on 30 mg), fatigue (n=5), diarrhea (n=3), vomiting (n=2), hyponatremia (n=2), oral cavity pain (n=2), and nausea, constipation, abdominal pain, headache, and hypothyroidism (all n=1). Gr 4 toxicities include: CNS hemorrhage (1 pt., 45 mg dose), lipase (1 pt) and hypertriglyceridemia (1 pt). No cardiac toxicities, bowel perforations, fistulas have been reported. Grade 1 or 2 abnormalities of thyroid function tests were reported in 10 pts and responded to thyroxine replacement therapy. 2 pts had grade 1 thyrotoxicosis. Tumor responses: 5 pts have had confirmed PR's (2 pts with plat-sens and 3 plat-resis) lasting 8, 11, 11, 12, and 25 weeks (overall RR of 18.5%), and 3 SD lasting 30, 27+, and 24 weeks. Of the remaining 19 pts, 2 pts had 28% decrease (lasting <16 weeks) and 27% decrease in disease after 2 cycles, 1 too early, 9 were removed for toxicities, and 7 had PD. Conclusions: Cediranib is an active drug in recurrent ovarian cancer; cediranib has predictable toxicities observed with other TKI's and warrants further study. No significant financial relationships to disclose.
CT perfusion as index of activity of antiangiogenic treatment of metastatic carcinoma
Authors: S. Vignot, J. Spano, J. Bloch, R. Mouawad, J. M. Foult, V. Adam, C. Soubrane, D. Buthiau, D. Khayat
Journal: Journal of Clinical Oncology (2008)

3548 Background: the aim of this study was to evaluate the different Computed Tomography (CT) parameters, characterizing tissue perfusion by contrast medium in metastatis to define their relation with activity of an antiangiogenic compound, targeting the VEGF receptors 1 and 2, using this qualitative and quantitative method. Methods: 113 patients with metastatic renal cell, pancreatic, colonic carcinoma and melanoma treated with antiangiogenic compound, were studied by dynamic CT (64 slices, GE) : calculation of time to peak (TTP), positive enhancement integral (PEI), maximum slope of increase (MSI), maximum slope of decrease (MSD), blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS) were performed. Value distributions in the normal and neoplastic wall, their variation after antiangiogenic therapies and their relation to mono and bidimensionnal or volume measurement and pathological vessel density (MVD) were evaluated. Results: BF, TTP, and especially PEI and PS were highter in tumor than in normal liver, respectively in 68, 76, 100 and 100%; PS was > 20 ml/min/100g in 100% of patients. PEI and PS decrease in 78% and 82% of patients submitted to antiangiogenic treatment at the first course. Decreased tumor perfusion (TP) was observed in patients responding to therapy, including liver metastasis. Furthermore, in 40 out of 60 patients with stable or progressive disease by RECIST, decreased TP was strongly correlated with clinical improvement. Significant correlation between PEI in tumor/PEI in the aorta and PS was found (R=0,679). Conclusion: CT perfusion could be reliable in the study of the neo-angiogenic process, characterized by an increase in vessel number, vascular permeability and flow into extra vascular spaces, better than direct measurement of the tumor or MVD count. Imaging will gain a role in monitoring targeted therapies, in the assessement of the evaluation of the antiangiogenic therapy and in the selection of patients eligible to be treated by this method. PEI in the tumor/PEI in the aorta and PS seem to be the most discriminative and predictive parameters. Others parameters (TTP, MSI, MSD) are operator and patient dependant. MTT is under evaluation as a good criterium of intersticial pressure around tumors No significant financial relationships to disclose.