tbuckley/cabot-search huggingface dataset:
Chemotherapy versus hormonal treatment in patients with platinum and taxane resistant ovarian cancer: A NSGO study
Authors: G. Kristensen, J. Kaern, M. Baekelandt, T. Skeie-Jensensen, R. dePont Christensen, E. Åvall-Lundqvist, M. Bergdahl, R. Sandvei, T. Hoegberg, S. Grenmann
Journal: Journal of Clinical Oncology (2008)

5508 Background: For patients with early relapse of ovarian cancer response to further treatment is low and comparison to best supportive care is by far lacking. While the primary endpoint in the study is quality of life, progression free survival (PFS) is also important. Methods: 236 patients with platinum- and taxane resistant ovarian cancer were randomized 1:2 to either tamoxifen (40 mg daily) or chemotherapy. Before randomization, the treating clinician had to choose chemotherapy; either weekly paclitaxel (80 mg/m2q1w) or pegylated doxorubicin (Caelyx [C]) (40 mg/m2 q 4w). Patients were treated until progression or unacceptable toxicity. Response was evaluated every 8 week. Results: Out of 236 randomized patients, 21 never started treatment for various reasons. 73 received treatment with tamoxifen, 68 with weekly paclitaxel and 74 with C. Before randomization, 131, 63 and 42 had received one, two and three lines of chemotherapy, respectively. Dose reduction occurred in 4 (6%) and 7 (9%) patients receiving paclitaxel and C, respectively. For patients treated with tamoxifen, weekly paclitaxel and C, respectively, the following toxicity was reported: Nausea grade (G) 2–3 by 6, 6 and 19 patients, mucositis G 2 by 1, 1 and 8 patients, neuropathy G 2–3 by 1, 7 and 4 patients, PPE G 2–3 by 0, 0 and 15 patients, while other toxicity G 2–3 was reported by 0, 0 and 15 patients, respectively. Febrile neutropenia was noted in 2 patients treated with C. Median progression free survival was 62 and 87days for patients given tamoxifen and chemotherapy, respectively. (p=0.0405). For the 3 groups tamoxifen, paclitaxel and C the median time to progression was 62, 99 and 84 days respectively. Conclusions: For patients with platinum-and taxane resistant ovarian cancer chemotherapy, with weekly paclitaxel or pegylated doxorubicin, induce a small but statistically significant improvement of PFS, compared with tamoxifen. The given chemotherapy was well tolerated. Patients treated with C reported more toxicity than patients treated with weekly paclitaxel. No significant financial relationships to disclose.
Secondary cytogenetic changes in acute promyelocytic leukemia--prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: a Cancer and Leukemia Group B study.
Authors: J L Slack, D C Arthur, D Lawrence, K Mrózek, R J Mayer, F R Davey, R Tantravahi, M J Pettenati, S Bigner, A J Carroll, K W Rao, C A Schiffer, C D Bloomfield
Journal: Journal of Clinical Oncology (1997)

PURPOSE To examine, in newly diagnosed patients with acute promyelocytic leukemia (APL), the prognostic significance of secondary cytogenetic changes and the relationship between such changes and the two major promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) mRNA types. PATIENTS AND METHODS One hundred sixty-one patients with t(15;17)(q22;q11-12) enrolled onto Cancer and Leukemia Group B (CALGB) protocol 8461, a prospective study of cytogenetics in acute myeloid leukemia (AML), were studied. Eighty of these 161 patients were treated solely with chemotherapy and evaluated for response to treatment and survival. PML-RAR alpha mRNA type was determined using reverse transcriptase polymerase chain reaction (RT-PCR) in 56 patients. RESULTS The incidence of secondary cytogenetic abnormalities was 32%. Among 80 patients treated with chemotherapy, the presence of a secondary chromosome abnormality was associated with longer complete remission (CR) duration (median, 29.9 v 15.7 months; P = .03) and longer event-free survival (EFS) duration (median, 17.0 v 12.2 months; P = .03). There was no difference in overall survival (P = .28). In a separate group of 56 patients with both cytogenetic and molecular data, 32 had the type L PML-RAR alpha transcript (intron 6 PML breakpoint). Of these 32 patients, four (12.5%) had chromosome changes in addition to t(15;17), whereas 12 of 20 patients (60%) with the type 5 PML-RAR alpha transcript (intron 3 PML breakpoint) had secondary cytogenetic changes (P &lt; .001). CONCLUSION (1) Secondary cytogenetic changes do not confer a poor prognosis in APL patients treated with anthracycline/cytarabine (Ara-C)-based chemotherapy; and (2) A highly significant relationship exists between the PML-RAR alpha 5 isoform (intron 3 PML genomic breakpoint) and secondary cytogenetic changes in APL.
Intraoperative radiotherapy (IORT) as a boost during breast conserving surgery (BCS) using low kV X-rays: The first 5 years of experience with a novel approach
Authors: F. K. Wenz, G. Welzel, E. Blank, B. Hermann, V. Steil, M. Suetterlin, U. Kraus-Tiefenbacher
Journal: Journal of Clinical Oncology (2009)

626 Background: Recently, the concept of IORT during BCS has been introduced using linear accelerators, brachytherapy or dedicated mobile IORT devices generating fast electrons or low energy X-rays. Here, we report the first 5 years of a single center experience after introduction of a novel approach to deliver IORT as a tumor bed boost during BCS for breast cancer. Methods: 155 breast cancers in 154 women (median age 63 yrs, range 30 - 83 yrs, T1/T2 = 110/45, N0/N+ = 104/51) were treated between February 2002 and December 2007 at the University Medical Center Mannheim/University of Heidelberg, in whom IORT as tumor bed boost was applied using 50 kV X rays (20 Gy, INTRABEAM, Carl Zeiss Oberkochen, additional OR time about 45 - 60 min) followed by 46 - 50 Gy external beam whole breast radiotherapy (EBRT). Chemotherapy was given before EBRT. The median interval between BCS+IORT and EBRT was 10 wks. Median follow-up was 34 mon (max 79.6 mon, 1 pt lost to f/u). Overall survival (OS), local relapse free survival (LRFS) and disease free survival (DFS) were calculated at 5 yrs using the Kaplan Meier method. 81 patients were evaluated at 3 yr f/u for normal tissue effects using the LENT SOMA scoring system. Results: Ten patients have died, 2 pts suffered from in breast relapse and 8 pts developed distant metastases yielding a 5yr OS of 87.0%, a 5yr LRFS of 98.4% and a 5 yr DFS of 73.9%. Grade 3 fibroses of the tumor bed were detected in 6% of the patients after 3 yrs. Skin toxicity was mild (teleangiectases and hyperpigmentations in 6% each). Conclusions: IORT as a tumor bed boost using the INTRABEAM system yields low recurrence and toxicity rates when followed by external beam whole breast radiotherapy. [Table: see text]
Central assessment of ER, PgR and HER2 in BIG 1–98 evaluating letrozole (L) compared to tamoxifen (T) as initial adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer
Authors: B. B. Rasmussen, M. M. Regan, A. E. Lykkesfeldt, P. Dell’Orto, B. Del Curto, K. L. Henriksen, M. G. Mastropasqua, B. Thürlimann, G. Viale
Journal: Journal of Clinical Oncology (2007)

538 Background: The BIG 1–98 trial, a randomized double-blind Phase III trial, showed that L significantly improved disease-free survival (DFS) as compared with T. It is uncertain whether benefit of aromatase inhibitors vs. T differs according to PgR and/or HER2 status of the tumor. A central assessment of ER, PgR and HER2 was undertaken for BIG 1–98 to investigate this question. Methods: Paraffin-embedded primary tumor material was evaluable for 3650 (74%) of the 4922 patients (pts) randomized to the 2 monotherapy arms (L or T for 5 years; 51 months median follow-up). ER and PgR were measured by immunohistochemistry (IHC) and positivity was defined as =1% immunoreactive cells. HER2 expression was determined by IHC and positivity was confirmed by FISH. Cox modeling estimated hazard ratios (HR) comparing L vs. T on DFS and assessed treatment-by-covariate interactions. Results: By central assessment, 86% and 10% of tumors were classified as ER+/PgR+ and ER+/PgR-, respectively. Among these (n=3533), 7% were ER+/HER2+. DFS was superior in pts with ER+/PgR+ vs. ER+/PgR- tumors and in pts with ER+/HER2- vs. ER+/HER2+ tumors. The benefit of L vs. T did not differ by PgR (P=.48) or HER2 status (P=.55). Conclusion: In postmenopausal patients with ER+ tumors (=1% immunoreactive cells), of which 10% were PgR- and 7% HER2+, both PgR- and HER2+ status were associated with poorer DFS. The benefit of L over T was observed in all ER+ patients irrespective of PgR or HER2 status. In patients with ER+ tumors, PgR and HER2 status do not appear to be selection criteria for treatment with L vs. T. [Table: see text] No significant financial relationships to disclose.
An acute oncology model of care for the management of emergency admissions with previously undiagnosed cancer.
Authors: J. W. King, P. C. Leonard, R. M. Jennings, C. Ingham-Clark
Journal: Journal of Clinical Oncology (2010)

e19618 Background: A retrospective audit of inpatients found to have a diagnosis of cancer during their emergency admission in 2008 demonstrated that these patients had a poor prognosis (29/33 were treated palliatively). Despite this, they underwent multiple investigations (median 3) and blood tests (median 42), and had a prolonged length of stay (LOS) (median 19 days), as referral to Oncology was made only upon histological confirmation of cancer. The aim of this study was to improve the quality of the patient experience for inpatients diagnosed with cancer, by reducing unnecessary investigations and LOS. Therefore, an innovative patient pathway was developed, incorporating referral to Oncology within 24 hours of radiological evidence of cancer, prior to biopsy. Methods: The new pathway was piloted for 6 months. Primary endpoints: LOS, number of blood tests and investigations. Data was collected prospectively from electronic request forms for all inpatients diagnosed with cancer; costings were provided by the finance department. Endpoints were compared to the previous audit population (group 1) using Mann Whitney U (MW U) analysis of non parametric data. Results: Of 18 inpatient cancer diagnoses, 12 (group 2) were referred to Oncology under the new protocol. Median LOS in groups 1 and 2 was 19 (range 4-97) and 10.6 (range 5-29), respectively; the distributions in the two groups differed significantly (MW U = 278, n1 = 33 n2 = 12, p <0.05 two-tailed). Median number of blood tests was significantly different between groups 1 and 2 at 42 (range 6-215) and 29 (range 9-82), respectively (MW U = 467, p <0.05 two-tailed). The number of investigations was not significantly different: median was 3 and 2.5 for groups 1 and 2, respectively (p >0.05). The median cost per admission for groups 1 and 2 was £6613 and £4462, respectively (p >0.05) Conclusions: In a patient population for whom prognosis is poor and quality of life is paramount, LOS can be reduced, blood tests avoided and the quality of the patient experience improved by earlier Oncology input. This also translates into a saving of over 200 bed days per year, which may also incur cost savings. No significant financial relationships to disclose.
Preliminary results of an open-label study to evaluate the efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with carboplatin-containing chemotherapy regimen in patients with ovarian cancer
Authors: P. F. Timmins, D. Kredentser, K. C. Hancock, M. Messing, K. A. Boehm, S. Mull, D. Ilegbodu, L. Asmar
Journal: Journal of Clinical Oncology (2007)

19652 Background: The use of aprepitant has been shown to offer an advantage in preventing acute and delayed chemotherapy- induced nausea and vomiting (CINV). This study integrates palonosetron and dexamethasone into the regimen to determine the efficacy and safety of this combination. Methods: 50 patients (pts) have enrolled; data has been submitted for 43. Main inclusion criteria were: diagnosis of ovarian (OV), primary peritoneal (PP), fallopian tube (FT) carcinoma Stage I-IV, or papillary serous cancer of the uterus (UPSC); naive to emetogenic chemotherapy Hesketh ≥Level 4, is scheduled to receive paclitaxel 175 mg/m 2 IV and carboplatin AUC=6 IV; is able to read and understand the Functional Living Index - Emesis (FLIE) questionnaire. Results: Median age was 61 years, 60% ECOG=0, 86% prior surgery; 68% OV, 14% PP cancers, 7% UPSC, and 5% FT. Metastases were noted in 30% of pts, 21% had visceral metastasis. To date, 70% of patients (32/46) have reported no vomiting, or use of rescue medications during the study and are deemed as complete responders. Based on the 35 pts for whom complete patient diaries have been submitted thus far, the complete response rate is 91% (32/25), compared to 50% (aprepitant alone [The MEC Trial]). No Grade 3–4 treatment related adverse events were reported; Grade 1–2 toxicities included neutropenia (10.5%); anemia, constipation, and nausea (7.9%, each), and fatigue, dyspepsia, and arthralgia (5.3%, each). Some of the toxicities may be related to the chemotherapy, and are not treatment-related to the aprepitant, palonsetron, or dexamethasone. Conclusions: The addition of aprepitant to palonsetron and dexamethasone appears to be very well tolerated. This combination is effective in the prevention of chemotherapy-induced nausea and vomiting when used with emetogenic therapy such as paclitaxel and carboplatin. This research was supported, in part, from a research grant from Merck &amp; Co., Inc. Whitehouse Station, NJ. No significant financial relationships to disclose.
Humoral shift and increased early recurrence with GM-CSF + vaccine versus vaccine alone
Authors: M. B. Faries, R. Essner, X. Ye, M. Hoban, D. L. Morton
Journal: Journal of Clinical Oncology (2008)

3013 Background: Vaccines are currently under evaluation in melanoma, and many vaccine strategies use GM-CSF as an immune adjuvant. There are few randomized data yet available to determine the clinical impact of the addition of GM-CSF to vaccination. We conducted a randomized, prospective trial of an allogeneic melanoma vaccine with or without GM-CSF to determine the immune and clinical effects. Methods: 95 patients were stratified by stage and randomized to Canvaxin vaccine (with bacille Calmette-Guerin [BCG]) or Canvaxin (+BCG) and GM-CSF (200 mcg/m2/d) injected at the vaccine sites after vaccination for 5 days. Antibody titers against a urinary tumor-associated melanoma antigen were measured by ELISA, and DTH skin testing was done using PPD and unadulterated vaccine cells. Results: There was a significant early rise in both IgG and IgM titers in the GM-CSF arm with an early high plateau at about 8 weeks for both. The rise in antibody titer was slower in the non-GM-CSF arm with IgG rising throughout the study period and IgM peaking at 20 weeks. Conversely there was a delay in PPD responsiveness in the GM-CSF arm. PPD conversion percentage surpassed 90% in the non-GM-CSF arm at 6 weeks and peaked at 100% at 12 weeks. In the GM-CSF arm, only 76% converted at 6 weeks and only 87% were ever sensitized. A trend toward diminished DTH response was noted in the GM-CSF arm as early as 4 weeks and became significant at 16 weeks (p=0.01) and when considered throughout the trial. There was a marked increase in early recurrences in the GM-CSF arm leading to a significant survival difference when examined at 2 years (96% versus 72%; log-rank p=0.0017). Conclusions: When given at the site of vaccination, GM-CSF appears to accelerate the onset of a humor immune response while delaying cellular responses. In addition there appears to be evidence of adverse clinical effects in terms of early recurrence and possibly survival. Recent reports of increased myeloid suppressor cells with GM-CSF treatment may provide an immune mechanism for our findings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration CancerVax
Frontline gemcitabine and cisplatin based chemotherapy in patients with NSCLC inoperable brain metastases
Authors: V. Quadvlieg, L. Bosquee, M. Gustin, N. Barthelemy
Journal: Journal of Clinical Oncology (2004)

7117 Background: Inoperable brain metastases in NSCLC treated with whole brain radiotherapy (WBR) reach a median survival shorter than 6 months. We have proposed in this situation, a frontline chemotherapy association. The purpose of this study is to evaluate the efficacy of gemcitabine and cisplatin in the treatment of NSCLC patients with unresectable brain metastases. Patients and methods: Patients with NSCLC and unresectable CNS metastasis, after signed informed consent, received gemcitabine 1000 mg/m2 and cisplatin 50 mg/m2, both delivered on days 1 and 8, every 3 to 4 weeks. Results: 40 consecutive patients were enrolled in our institution. 35 chemotherapy-naïve had synchronous brain metastases. 5 patients were enrolled after brain relapse following previous chemotherapy (disease free interval: mean: 13.2 months, range: 9–26). 3 patients are not evaluable because of early death, after 0, 6 and 8 weeks, respectively. After 2 cycles, the response rate (RR) in brain metastases was 62% in 36 evaluable patients. After 4 cycles the RR was 86% in 21 evaluable patients . With 9 complete responses and 14 partial responses, the overall RR was 64%. 2 patients had stable disease. All but 3 of the responding patients had a response on their primary lung tumor lesion. The mean duration of response was 6.8 months and the overall mean survival is 6.0 months overall and 7,2 months in responding patients. Toxicity: no infection, no bleeding, no non-hemato toxicity > gr2 was seen; no particular CNS toxicity post RT was noticed (46% of the patients received WBR) . Conclusions: This chemotherapy regimen shows encouraging activity in NSCLC patients with inoperable CNS metastases. We will present the general characteristics and prognostic factors of these patients in june 2004. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly
Angiotensin-(1–7), a small molecule inhibitor of glioblastoma growth
Authors: G. J. Lesser, K. A. Carver, S. J. Newton, E. A. Tallant, P. E. Gallagher
Journal: Journal of Clinical Oncology (2009)

2024 Background: Recent studies suggest that anti-angiogenic therapies may be effective in patients with glioblastoma multiforme (GBM), a highly vascular tumor. We have previously demonstrated that angiotensin-(1–7) [Ang-(1–7)], an endogenous heptapeptide with anti-angiogenic properties, significantly reduced the serum-stimulated growth of three human glioblastoma cell lines which contained mRNA for the AT (1–7) receptor mas. We now provide the first evidence that Ang-(1–7) markedly decreases the proliferation and growth of human glioblastomas in vivo using a xenograft model. Methods: Athymic mice with tumors resulting from injection of human U87 glioblastoma cells were treated for 18 days with saline or 1000 μg/kg Ang-(1–7), delivered by subcutaneous injection every 12 h. Results: The average volume of the tumors from mice treated with the heptapeptide was approximately 3-fold less than the size of the tumors from control animals (586.1 ± 94.5 mm 3 vs 1845.5 ± 238.1 mm 3 ; n = 6, p &lt; 0.05). Further, the tumors from mice injected with Ang-(1–7) weighed almost 50% less than the tumors from mice treated with saline (1.31 ± 0.12 g vs. 2.45 ± 0.23 g; n = 6, p &lt; 0.05). The Ang-(1–7)-mediated reduction in tumor growth was associated with a significant decrease in immunoreactive Ki67, a proliferation marker. In addition, a marked down-regulation of cyclooxygenase 2 (COX-2), prostaglandin E synthase (PGES-1) and vascular endothelial growth factor (VEGF) was observed in tumors from Ang-(1–7)-injected mice compared to saline-treated controls (COX-2: 1.00 ± 0.06 vs 0.55 ± 0.07 relative gene expression; PGES-1: 1.03 ± 0.08 vs. 0.40 ± 0.06; VEGF: 1.05 ± 0.07 vs. 0.59 ± 0.09; n = 6, p &lt; 0.05) with no effect on COX-1 or PGI synthase mRNA. Conclusions: These results suggest that Ang-(1–7) may reduce the concentration and ratio of proliferative and anti-proliferative prostaglandins to decrease glioblastoma growth as well as attenuate angiogenesis through a reduction in VEGF. Thus, Ang-(1–7) may be a new, first-in-class small molecule inhibitor for the treatment of glioblastoma, providing combination therapy as a selective COX-2/PGES-1 and angiogenic inhibitor, targeting a specific AT (1–7) receptor mas. No significant financial relationships to disclose.
Relationship of Injury to Chemical Carcinogenesis in the Lungs of Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W. K. Blenkinsopp
Journal: JNCI Journal of the National Cancer Institute (1968)

Carcinogen was deposited in the lungs of rats, with or without various types of lung damage, to assess the significance of lung damage in the etiology of lung cancer. Rats given a depot injection of 5 mg 3-methyl-cholanthrene (MCA) directly into the lung developed lung cancer. When MCA was suspended (partly dissolved) in hexachlorotetrafluorobutane (which produces pulmonary infarction) and given by intravenous injection, large doses, 2.2 mg MCA, induced lung cancer but smaller doses, 1.6 mg MCA, did not. When MCA in arachis oil was injected intravenously and lung damage was produced separately, lung cancer did not develop. It was concluded that induction of lung cancer in rats depends on an adequate local dose of carcinogen and that epithelial proliferation produced by lung damage plays little or no part. The mechanism of lung cancer induction in man appears to be similar.
Intratumoral injection of oncolytic adenovirus H101 in combination with vinorelbine/cisplatin chemotherapy in patients with advanced non-small cell lung cancer
Authors: C. Zhou, Y. Xu, J. Ni, S. Zhou, J. Xu
Journal: Journal of Clinical Oncology (2006)

17082 Background: Chemotherapy is main treatment for advanced NSCLC. But its efficacy is quite small with improvement of 1–2 months in median survival. New strategy against NSCLC is needed. Oncolytic adenovirus H101 is found to be effective against NSCLC. This trial is desigened to investigate efficacy and toxicity of intratumoral injection of H101 in combination with chemotherapy in the treatment of NSCLC. Methods: The NSCLC patients confirmed cytologically or pathologically were randomized to intratumoral injection of adenovirus H101 (1.5 × 1012 viral particles) plus NP chemotherapy (arm A) or NP chemotherapy (arm B). Objetive response was evaluated every two cycles and time to progression (TTP) and overall survival were followed up. Results: Out of 18 evaluable patients in Arm A, 4 patients showed partial response (PR),3 minor response(MR), 7 stable disease (SD) and 4 disease progression (PD), while in Arm B 16 evaluable patients showed 3 PR, 4 MR, 3 SD and 6 PD. At the first time of response evaluation, there was 1 PD in Arm A,but in Arm B there were 5 of PD. Failure rate in Arm B was significantly higher than in Arm B. Survival curves between the two arms were similar. Six month, 9 month and 1 year survival rates were slightly higher in Arm B and median TTP was also prolonged in Arm A. Except non-infectious fever, Arm A was similar in other toxicities to Arm B. there was only 2 patients developing mild pneumothorax. Conclusions: Intratumoral injection of H101 1.5 × 1012 viral particles in combination with NP chemotherapy was feasible, effective and safe in treatment of advanced NSCLC. No significant financial relationships to disclose.