tbuckley/cabot-search huggingface dataset:
Randomized phase II trial comparing every-3-week carboplatin/paclitaxel (C/P) versus every-3-week C with weekly P in advanced non-small cell lung cancer (NSCLC)
Authors: H. B. Niell, M. A. Socinski, K. Bakri, J. Wall, M. Baggstrom, M. Escudero, A. Mears, M. Tynan, A. Ivanova
Journal: Journal of Clinical Oncology (2004)

7073 Background: C/P remains a commonly used regimen in advanced NSCLC although the optimal dose/schedule of both agents remains controversial. We designed a randomized phase II trial addressing a pure schedule question over 4 cycles of C/P in the first-line setting. Methods: Patients (pts) with stage IIIB/IV NSCLC are randomized to either C AUC 6 plus P 225 mg/m2 every 3 weeks for 4 cycles (Arm A) or C AUC 6 every 3 weeks for 4 cycles with P 75 mg/m2/wk x 12 (Arm B). Total cumulative doses of P on both arms are identical as is the schedule of C. The FACT-L QoL instrument is being performed at baseline and at 6 and 12 weeks while on C/P. Results: Thus far, 145 of a planned 160 pts have been randomized (Evaluable thus far, n= 67 Arm A, n= 69 Arm B). Patient characteristics: median age 60 yrs (range 38–85), 64% male, 89% stage IV: 11% IIIB, 52% KPS 70–80; 48% KPS 90–100%, 51% > 5% wt loss. All characteristics are well balanced between the arms. A median of 4 cycles have been delivered on Arm A and 12 wks of weekly C/P on Arm B. Grade 3/4 hematologic toxicities are not significantly different between the two arms. Grade ≥ 2 non-hematologic toxicities are not significantly different except for myalgia/arthralgia which was less frequent on Arm B (4% Arm B vs 18% on Arm A, p=0.03). Rates of ≥ grade 2 neuropathy are 15% and 12% on Arm A and B, respectively (p=0.8). Response rates (RR) are 28% on Arm A and 35% on Arm B (stable disease rates are 39% and 33%, respectively). Median survival of all pts thus far is 8.3 months (95% CI, 6.4–9.0) with a median survival of 7.3 months (95% CI, 5.9–8.6) and 8.7 months (95% CI, 6.5–10.4) for Arms A and B, respectively. The QoL information from the FACT-L will be presented. Conclusions: 1) Weekly C/P given on this schedule has less non-hematologic toxicity in the form of myalgia/arthralgia, 2) RR and overall survival are similar on both the arms of the trial, 3) This schedule and dose of weekly paclitaxel in combination with C every-3-wks appears active and well-tolerated in advanced NSCLC Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Case Records of the Massachusetts General Hospital (Case 9-1996)
Journal: New England Journal of Medicine (1996)

A case study of a women who complained of abdominal pain 9 weeks after laparoscopic tubal ligation and discontinuation of oral contraceptives (OCs) is discussed.  A hepatic mass was discovered and excised.  The possible role of OCs in the development of the hepatic lesion in this women is discussed.
The PARADIGM trial: A phase III study comparing sequential therapy (ST) to concurrent chemoradiotherapy (CRT) in locally advanced head and neck cancer (LAHNC): Preliminary toxicity report.
Authors: R. I. Haddad, R. B. Tishler, D. Adkins, F. R. Khuri, J. Clark, J. H. Lorch, L. J. Wirth, N. J. Sarlis, Z. Jaffa, M. R. Posner
Journal: Journal of Clinical Oncology (2010)

5563 Background: PARADIGM is a multicenter phase III study comparing TPF (docetaxel, cisplatin, and 5-fluorouracil)-based ST (Arm A) to upfront cisplatin CRT (Arm B) in patients (pts) with LAHNC. Pt accrual was terminated in 12/08 due to slow enrollment. We present here preliminary data on encountered toxicities. Methods: Pts were randomized to receive ST (as induction chemotherapy with TPF × 3 and then CRT with either weekly carboplatin or docetaxel) or CRT (cisplatin × 2). Standard toxicity assessments were performed. Data were collected from the time of study entry until Dec, 2009. Results: A total of 145 pts were enrolled (Arm A: 70; Arm B: 75), of whom 127 were male, and 127 were Caucasian. Median age was 55; patients had PS of 0 (97) or 1 (48). Sites of disease were: oropharynx: 80, larynx: 24, hypopharynx: 15, and oral cavity: 26. Disease stage was either III (74 pts) or IV (70 pts). After a median follow-up of 34 months, toxicity encountered is as follows: In Arm A: febrile neutropenia: grade (G) 3 and 4 in 10 and 6 pts; pain: G2, 3 and 4 in 26, 1 and 1 pts; xerostomia: G2 and 3 in 23 and 5 pts; and neuropathy: G1and 2 in 17 and 5 pts, respectively. In arm B: febrile neutropenia: G4 in 1 pt; xerostomia: G2 and 3 in 23 and 5 pts; and neuropathy: G1, 2 and 3 in 11, 7 and 2 pts, respectively. A total of 111 pts had a feeding tube placed (Arm A: 53; Arm B:58) with 31 pts still have a feeding tube at the time of analysis (Arm A: 15; Arm B:16). A total of 4 patients in Arm A died within the first year: Two died following CRT at 1 and 8 mo post-therapy and two died during induction, one of whom discontinued therapy after one cycle of chemotherapy and died 2 months later. One patient in Arm B died following CRT. Conclusions: This preliminary report of data from the PARADIGM trial does not reveal any unusual pattern of toxicities in either arm, and confirms the feasibility of TPF-based ST in pts with LAHNC. Analysis of late toxicities and study outcomes is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis Amgen, Pfizer, sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis
Impact of baseline characteristics on efficacy and safety after bortezomib-based induction and maintenance in newly diagnosed multiple myeloma (MM) patients ineligible for transplant in the phase IIIb UPFRONT study.
Authors: R. Niesvizky, I. W. Flinn, R. M. Rifkin, N. Gabrail, V. Charu, Y. Gaffar, R. Neuwirth, D. Corzo, J. Reeves
Journal: Journal of Clinical Oncology (2011)

8072 Background: The multicenter, phase IIIb UPFRONT study compares the efficacy and safety of 3 bortezomib (Vc)-based induction regimens, VcD (Vc–dexamethasone), VcTD (Vc–thalidomide–dexamethasone) and VcMP (Vc–melphalan–prednisone), followed by weekly Vc maintenance, in newly diagnosed MM patients ineligible for HDT–SCT. Methods: Patients were randomized (1:1:1) to receive 8 three-week cycles of induction followed by 5 five-week cycles of maintenance. Efficacy and safety data were analyzed by patient and disease baseline characteristics including age, gender, Charlson comorbidity index (CCI) and ISS stage after 300 patients (100 patients per arm) had the opportunity to complete all 13 cycles. Data were pooled across all three treatment arms. Response was assessed using IMWG criteria. AEs were graded by NCI-CTCAE v3.0. Results: Rates of ≥VGPR were higher in patients age <75 years (p=0.034). Patients with a CCI of 0 showed a trend to better ≥VGPR (p=0.078). A multivariate analysis showed similar results. There was no significant difference in ≥VGPR by gender, race, or ISS stage. Grade ≥3 AE rates appeared lower in patients <75 years, and PN rates (all grade) tended to be lower in males and in white patients. There were no apparent trends in the rates of grade ≥3 AEs or PN (all grade) by CCI or ISS stage. Previous reports from this study have shown that ≥VGPR rates were similar by treatment arm, but that rates of grade ≥3 AEs and PN were higher in the VcTD arm (Niesvizky, ASH 2010). Conclusions: The results of this subgroup analysis show that patients <75 years had higher rates of ≥VGPR and lower rates of grade ≥3 AEs in the UPFRONT study. These results suggest that Vc-containing regimens are active across various patient subgroups including gender, race, co-morbidity status, and ISS stage. Baseline characteristic N ≥VGPR (%) P value* <75 years 157 48 0.034 ≥75 years 100 35 Male 137 40 0.292 Female 120 47 White 192 43 0.789 Nonwhite 65 45 CCI 0 146 48 0.078 CCI ≥1 111 37 ISS 1 62 45 0.238 ISS 2 111 40 ISS 3 72 51 * Univariate chi-square p value.
THE PRODUCTION OF PURPURA BY DERIVATIVES OF PNEUMOCOCCUS
Authors: Hobart A. Reimann, Louis A. Julianelle
Journal: The Journal of Experimental Medicine (1926)

A study has been made of the variation in number of the blood platelets, and the red and white blood cells of white mice injected with pneumococcus extract. The blood platelets were greatly diminished after the injection, the greatest decrease usually occurring after 24 hours. Purpuric lesions usually developed when the number of blood platelets became less than 500,000 per c.mm. Regeneration of the platelets was accomplished by the 4th to the 9th day but there was an overregeneration and the return to normal did not take place until 2 weeks had elapsed. The red cells were also greatly reduced in number, but the rate of their destruction and regeneration was somewhat slower than that of the platelets. The leucocytes were slightly if at all influenced by the pneumococcus extract. Pneumococcus extracts were shown to be thrombolytic and hemolytic. Heat destroyed the activity of both the lysins in vitro. Heated extract produced purpura in mice but did not cause a severe anemia. Extracts adsorbed with either blood platelets or red blood cells showed a marked diminution in their thrombolytic and hemolytic activity in vitro. Such extracts, however, produced purpura as well as severe anemia and thrombopenia in mice.
T-Cell Involvement in Adoptive Transfer of Line 10 Tumor Immunity in Strain 2 Guinea Pigs
Authors: W H de Jong, P A Steerenberg, M M van de Plas, W Kruizinga, J Ruitenberg
Journal: JNCI Journal of the National Cancer Institute (1985)

Several aspects of adoptive transfer of tumor immunity were studied in the line 10 hepatocarcinoma in the syngeneic Sewall-Wright strain 2 guinea pig. In particular, the need for cooperation between donor and recipient T-cells was investigated. Donor immune spleen cells remained immunologically capable of inducing tumor rejection for at least 160 days after adoptive transfer. Irradiated (1,000 rad) or mitomycin-treated immune spleen cells lacked tumor-rejection activity, which is indicative of the necessity for in vivo proliferation after adoptive transfer of immunity. Furthermore, adoptive transfer of tumor immunity was abrogated after treatment of the line 10 immune spleen cells with rabbit anti-guinea pig-thymocyte serum (ATS) plus complement. The role of recipient T-cells was investigated in strain 2 guinea pigs which were T-cell depleted by thymectomy, irradiation, and bone marrow reconstitution (T-XBM animals). Severe suppression of T-cell activity was present at 2 and 6 weeks after irradiation and bone marrow reconstitution. At 10 weeks nonspecific T-cell activity was partially restored. The induction of antigen-specific responses, measured by delayed-type hypersensitivity skin testing in vivo and antigenic stimulation in vitro, was suppressed at 2 weeks after irradiation and bone marrow reconstitution. Additional in vivo treatment of T-XBM animals with a rabbit ATS improved the T-cell depletion only moderately. Tumor growth and tumor rejection after adoptive transfer of immunity were equal in normal and T-cell-deprived recipient animals, thus indicating that recipient T-cells are not needed for tumor rejection after adoptive transfer of line 10 tumor immunity.(ABSTRACT TRUNCATED AT 250 WORDS)
Vs-6063 (Defactinib) Targets Mesothelioma Cancer Stem Cells Directly and Through Inhibition of Tumor-Associated Macrophages and Cytokine Production
Authors: M. Keegan, J.E. Ring, V.N. Kolev, I.M. Shapiro, M.V. Padval, Q. Xu, J.A. Pachter
Journal: Annals of Oncology (2014)
MicroRNA-23a Curbs Necrosis during Early T Cell Activation by Enforcing Intracellular Reactive Oxygen Species Equilibrium
Authors: Baojun Zhang, Si-Qi Liu, Chaoran Li, Erik Lykken, Shan Jiang, Elizabeth Wong, Zhihua Gong, Zhongfen Tao, Bo Zhu, Ying Wan, Qi-Jing Li
Journal: Immunity (2016)
Impact of delayed orchiectomy (OE) on overall survival (OS) in patients (pts) with metastatic germ cell tumors (mGCT).
Authors: M. Fedyanin, A. Tryakin, D. Kanagavel, E. Burova, T. Zakharova, I. Fainstein, U. Sergeev, I. Pokataev, A. Garin, S. Tjulandin
Journal: Journal of Clinical Oncology (2010)

4584 Background: Classically OE is the first step of the treatment of mGCT. However some pts have severe symptoms of disease, which require immediate beginning of chemotherapy (CT) followed by OE. The retrospective analysis was performed to find any impact of time constraints of delayed OE on survival in pts with mGCT. Methods: We analyzed data of 1483 CT-naïve pts with advanced mGCT of testis treated in our department from 1986 to 2009. Delayed OE was performed on 71(4,8%) pts. Seminoma – 8 pts (11,2%), nonseminomatous tumor – 50 pts (70,4%), unknown histology – 13 pts (18,4%). Twenty, 40% and 40% of pts belonged to good, intermediate and poor IGCCCG prognostic groups respectively. Median time from the beginning of the CT to OE was 18 (range, 1-250) days. OE was performed on 39 (55%) pts during cycle 1, 11 (15.5%) pts - after completion of induction CT, other pts – during cycles 2-4. Median follow-up time was 156 (range, 3 - 241) months. Etoposide and cisplatin containing CT was performed on 66 pts (93%). Results: Three-year OS for all 1,478 pts was 75%. Primary tumor had excellent response to CT: among pts who had delayed OE after completion of CT (n=11) only mature teratoma (n=4) and necrosis (n=7) were found. The 3-year OS in pts with delayed OE was 63%. OE performed after completion of CT was associated with better prognosis. The 3-year OS in pts with delayed OE performed during the 1st cycle (group 1) was 67%, during 2nd – 4th cycles of CT – 39% (group 2), and after completion of CT – 88% (group 3) (groups 1 vs. 3: HR 3,7, 95% CI 0,69 to 10,1, g=0,15; groups 2 vs. 3: g=0,01, HR 8,1, 95% CI 1.32 to 18.72). It seems that if OE had been performed during CT, the beginning of next cycle was delayed and dose intensity of CT was decreased. Conclusions: In case of severe symptoms of disease, which require an immediate start of CT, performing OE simultaneously with other surgeries after completion of induction CT was associated with better OS, when compared with performing OE during induction CT. No significant financial relationships to disclose.
Randomized run-in study of bevacizumab (B) and everolimus (E) in low- to intermediate-grade neuroendocrine tumors (LGNETs) using perfusion CT as functional biomarker.
Authors: J. C. Yao, A. T. Phan, D. Fogleman, C. S. Ng, C. B. Jacobs, C. D. Dagohoy, C. Leary, K. R. Hess
Journal: Journal of Clinical Oncology (2010)

4002 Background: Studies have shown promising results for mTOR inhibitor, E, and VEGF inhibitor, B, in LGNETs. In our prior study, decrease in tumor blood flow (BF) following B was proportional to baseline BF suggesting B decreased BF by a fixed percentage. Methods: LGNET patients with lesion(s) ≥ 3 cm were randomized to therapy with B or E for one 21-day cycle. On cycle 2 day 1, the alternate agent was added (B+E). Functional CTs (fCTs) assessing tumor BF, blood volume (BV), mean transit time (MTT), and permeability surface (PS) were mandatory. Primary objectives were to determine the effects of B or E as well as B+E on BF. Response was evaluated by RECIST every 9 weeks. Results: 112 fCTs were performed among 39 eligible (treated) patients. 64 lesions among 36 patients were evaluated at 3 time points. B alone led to a 32% decrease in BF (p<0.01) and no significant change in MTT. E alone was associated with increase in MTT (13%; p=0.02) but not with decrease in BF. Addition of E to B led to a further decrease in BF (15%; p=0.02) and increase in MTT (22%; p<0.01). Addition of B to E resulted in a 21% decrease in BF (p=0.01) and no significant change in MTT. By ITT analyses, there were 10 PR (26%), 27 SD (69%), 1 PD (3%), 1 not assessable (3%). PFS rate at 6-month was 92%; median was 14.4 months (95% CI, 12.7-16.1). The 12- and 24-month overall survival rates were 92% and 87% (median not reached). RECIST PR was associated with fCT parameters (all p<0.05) including: higher baseline permeability surface, higher post-treatment MTT, higher percentage decrease in BF, BV, and higher percentage increase in MTT. CTC G3/4 AE occurring in 2 or more patients included: neutropenia (15%), proteinuria (10%), hyperglycemia (10%), anemia (8%), and 5% in each of thrombocytopenia, elevated ALT, elevated AST, fatigue, GI bleed, hypertriglyceridemia, infection, nausea, vomiting, small bowel obstruction, pneumonitis, weight loss. Conclusions: B decreased tumor BF. Addition of E to B was associated with further decrease in BF. B+E demonstrated antitumor activity in LGNET. fCT is a promising surrogate marker for selection of patients likely to benefit from therapy. Confirmatory studies are warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis GE Healthcare, Genentech, Novartis
IFCT-0504 trial: Mucinous (M) and nonmucinous (NM) cytologic subtypes interaction effect in first-line treatment of advanced bronchioloalveolar carcinoma (BAC) by erlotinib (E) or carboplatin/paclitaxel (C/P).
Authors: J. Cadranel, R. Gervais, M. Wislez, P. Merle, D. Moro-Sibilot, V. Westeel, L. Bigay-Game, E. A. Quoix, S. Friard, F. Barlesi, M. Zaegel, L. Moreau, I. Monnet, J. Duhamel, G. Oliviero, P. J. Souquet, L. Thiberville, L. Baudrin, F. Morin, G. Zalcman
Journal: Journal of Clinical Oncology (2011)

7521 Background: First-line EGFR-TKI in advanced BAC yielded a 2.9 to 4-month PFS in Phase II trials. We have suggested that EGFR-TKI had a reduced activity in M-BAC but that C/P and pemetrexed could have some effect, in both cytological BAC subtypes. To determine the best therapeutic strategy for advanced BAC, we conducted a multicentric randomized phase II trial to evaluate in first-line treatment E (150 mg/d) or C/P (AUC 6 d1 / 90mg/m² d1,8,15 four-weekly) with a cross-over at progression and pemetrexed in third-line. Methods: Inclusion criteria: previously untreated, cyto/pathologically proven advanced BAC. Primary objective: 4-month disease control rate (DCR) >30% and PFS >3.0 months. Secondary objectives: tolerance, QOL, OS and subgroups analyses by arms, cytological subtypes and predefined biomarkers. Results: From 09/06 to 07/09, 130/133 patients were eligible: median age (68 yrs), PS <2 (87%), females (39%), never smokers (27%), stage IIIB-IV (91%), NM (46%), M (41%) and undetermined (13%) BAC. DCR was 46% (37-55), PFS=3.5 months (2.6-5.6) and OS=19.5 months (12.1-28.7). Grade ≥3 toxicity (>5%): skin for E and hematological/febrile neutropenia and neuropathy for C/P; 1 death-related toxicity with E. DCR and PFS were independently associated with smoking (p=0.008 and p=0.02), respiratory symptoms score (p=0.01 and p=0.004). DCR was also associated with age >70 yrs (p=0.03) and PFS with treatment arms (p=0.03). Although PFS improved with C/P compared to E (HR=0.667 [0.461-0.966], p=0.03), OS did not differ between the two arms (21.0 [15-33] and 16.4 [12-29] for E and C/P, respectively). Finally, an independent interaction (p=0.035) was observed for the PFS, between treatment arms and cytological subtypes. Increased risk of progression was observed with E compared to C/P for M-BAC (HR=2.7 [1.4-5.1], p=0.003), but not for NM-BAC (HR=0.90 [0.51-1.54]). Conclusions: IFCT-0504 trial showed that: 1) C/P is effective in both M- and NM-BAC; and 2) E is as effective as C/P in NM-BAC, but less in M-BAC. Finally, it suggested that strategy including C/P and E contributed to improve survival in advanced BAC.
Phase II study of amrubicin, a new active drug in refractory or relapsed small-cell lung cancer (SCLC): Thoracic Oncology Research Group Trial 0301
Authors: T. Seto, N. Masuda, Y. Takiguchi, H. Isobe, H. Okamoto, T. Ogura, A. Yokoyama, K. Watanabe, K. Eguchi
Journal: Journal of Clinical Oncology (2006)

7060 Background: Amrubicin, a totally synthetic 9-aminoanthracycline, is a topoisomerase II inhibitor. The response rate to amrubicin at 45 mg/m 2 on days 1–3 in chemotherapy-naive patients with extensive stage SCLC was 75.8% on an intent-to-treat analysis, with major dose-limiting toxicities of neutropenia, anemia, thrombocytopenia, and anorexia. The very high activity of amrubicin as a single agent in this disease led us to carry out the phase II trial reported here, which was designed to determine the antitumor activity and toxicity of amrubicin in previously treated pts with SCLC. Methods: Pts with cytologically or histologically proven SCLC who were previously treated with at least one platinum-based chemotherapy and ECOG PS 0–2 were eligible. They received amrubicin 40mg/m 2 intravenously on days 1–3 every 3 weeks. The primary end-point was the response rate, which determined the sample size of 44 pts in the sensitive cases and 15 pts in the refractory cases, respectively. Secondary objectives were to determine the progression-free survival, overall survival, and 1-year survival rate. Results: In total, 60 pts consisting of 44 sensitive cases and 16 refractory cases with median age 67 years (range 52–79) and 46 out of 60 male were enrolled. The median treatment cycles were 4 (1–8). Grade 3/4 hematological toxicity per patient (pt) was neutropenia (83%), thrombocytopenia (20%) and anemia (33%). Febrile neutropenia was observed in 3 pts. Grade 3/4 non-hematological toxicity per pt was pneumonia (3%), anorexia (15%), low Na levels (8.3%), pneumonitis (1.7%) and cerebral hemorrhage (1.7%). No treatment-related death was observed. The overall response rates were 52% (95% CI: 37–68) in the sensitive cases, and 50% (95% CI: 25–75) in the refractory cases. The progression-free survival, overall survival and 1-year survival in the sensitive cases and the refractory cases were 4.0 and 3.2 months, 11.7 and 10.9 months and 48.2 and 37.8%, respectively. Conclusions: Amrubicin has a significant activity in SCLC, particularly in pts refractory to prior chemotherapy, with predictable and manageable toxicities. Further studies to evaluate the survival benefit of amrubicin in this setting are warranted. No significant financial relationships to disclose.
Tumors of the Heart and Stomach Induced in European Hamsters by Intravenous Administration of N -Methyl- N -nitrosourea 2
Authors: M. Ketkar, G. Reznik, H. Haas, J. Hilfrich, U. Mohr
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Tumors of the Heart and Stomach Induced in European Hamsters by Intravenous Administration of N-Methyl-N-nitrosourea Get access M. Ketkar, M. Ketkar Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Reznik, G. Reznik Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Haas, H. Haas Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Hilfrich, J. Hilfrich Search for other works by this author on: Oxford Academic PubMed Google Scholar U. Mohr U. Mohr Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 6, June 1977, Pages 1695–1699, https://doi.org/10.1093/jnci/58.6.1695 Published: 01 June 1977 Article history Received: 02 August 1976 Accepted: 04 January 1977 Published: 01 June 1977