tbuckley/cabot-search huggingface dataset:
Gefitinib in heavily pretreated non small cell lung cancer: Results of the expanded access program in Eastern France
Authors: D. Spaeth, G. Deplanque, N. Favrot, N. Paillot, M. P. Lang, A. Cuguiliere, J. Seigneur
Journal: Journal of Clinical Oncology (2004)

7323 Background: Patients with NSCLC usually present or relapse with metastatic or unresectable disease resistant to standard therapy. Gefitinib is an orally active, selective tyrosine kinase inhibitor targeting the EGFR. Two large phase II monotherapy trials (IDEAL)-1 & (IDEAL)-2 have established Iressa as an effective therapy for NSCLC pts having failed chemotherapy (Cx). The present study evaluates the efficacy and safety of Iressa for pts treated through an EAP in Eastern France. Methods: pts were eligible if they had histologically proven NSCLC and had failed two or more prior Cx regimens at least one of which was platinum based. All patients gave written informed consent. Gefitinib was given 250 mg od. Therapies other than supportive care were not permitted. All patients were prospectively followed with monthly clinical examination, blood tests and chest X-ray. Results: 82 pts were eligible in 6 centers. Median age was 58 yrs (range, 34–79) with 49/33 M/F. Histological subtypes were epidermoid (21%), adenocarcinoma (67%) and other (12%). Median WHO PS was 2 (range, 0–4). The number of previous Cx regimens was 2 (35pts), 3 (36 pts), 4 or more (11 pts). 16 patients were not evaluable for response due to early death or insufficient follow-up. Among the 66 evaluable pts 3 PR were observed (4.5%), 26 pts experienced SD (39.4%) and 37 progressed, for a clinical benefit (PR + SD) in 43.9% of pts. Toxicity was mild with mostly grade1–2 diarrhoea, grade 1 xerodermia and grade 1–2 acneiform rash. No cases of interstitial pneumonia were suspected. Median duration of treatment was 2 mo (range, 0–11), 30 pts usually with poor PS having been treated for 1 mo or less. Median survival was 3 mo (range, 0.0–15+). Conclusion: Our results are similar to those reported in the global monotherapy trials IDEAL 1 & 2 with a disease control rate (including both tumor response and stable disease) of 44%. Our lower response rate (4.5% versus 19% for IDEAL 1) could be due to the fact that many pts were treated at a very advanced stage of disease, 30 could not complete more than one month of Iressa. This urges for an earlier use of Iressa in the course of the disease. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Neoadjuvant chemotherapy in advanced epithelial ovarian oancer (EOC): A phase III randomized study
Authors: L. Kumar, R. Hariprasad, S. Kumar, N. Bhatla, N. Shukla, S. Thulkar, R. Singh
Journal: Journal of Clinical Oncology (2006)

15000 Background: We compared upfront surgery to upfront chemotherapy in patients with advanced EOC (stage IIIC and IV (pleural effusion only). Factors- optimum debulking (residual disease ≤1cm) rate, surgical morbidity, chemotherapy toxicity, survival and quality of life (QOL) were analyzed. Methods: Between Oct.2001 and Oct. 2005, 90 newly diagnosed patients with advanced EOC have been randomized to upfront surgery followed by six cycles of paclitaxel + carboplatin (TC) (Arm A) or upfront chemotherapy - 3 cycles (TC) followed by surgery then 3 more cycles of TC. Eligibility criteria included- age 18 to 65 years, biopsy or cytological proven diagnosis of EOC and adequate hematological, renal, liver and cardiac functions. Upper and lower GI endoscopy and serum CEA was done in all patients to rule out GIT primary. QOL was assessed using FACT-O questionnaire at baseline, postop, post 3 cycles and post 6 cycles chemotherapy. Results: 78 of 90 patients have completed the treatment. Among 74 evaluable patients, optimal debulking rate was higher in the neoadjuvant chemotherapy arm (83% vs 13%, p &lt; .001). Blood loss during surgery (340 ml vs.485 ml, p &lt; . 008), mean operating time (69 minutes vs. 77 minutes, p = 0.22), post op infection rate (3% vs 17.5%, p &lt; .07), &amp; hospital stay (9 days vs. 12.4 days, P = 0.04) were lower in the chemotherapy arm. Operative mortality was higher in upfront surgery arm (7.7% vs 3.3%, p = .38). QOL score was higher post 3 cycles and post 6 cycles in the upfront chemotherapy arm (p &lt; . 0001). Grade III-IV GI toxicity (4.5% vs 3.8%) and myelo-suppression (7% vs 9%) was similar in two arms. At a median follow up of 33 months, Overall (41 vs 42 months) &amp; progression-free survival (35.3 vs 29 months,p = ns) are not significantly different in upfront chemotherapy vs upfront surgery arms, respectively. Conclusions: Upfront chemotherapy in advanced EOC results in significantly higher optimum debulking rate with reduced surgical morbidity and mortality, Quality of life score was also higher. Present study favors role of “upfront chemotherapy” in patients likely to have residual disease &gt;1cm and higher morbidity with upfront surgery. No significant financial relationships to disclose.
The association between the use of statin and breast cancer recurrence.
Authors: Y. Chae, M. E. Valsecchi, J. Kim, A. M. Desai, W. J. Tester
Journal: Journal of Clinical Oncology (2010)

1562 Background: There have been epidemiologic and biochemical findings alluding to the role of statin in reducing the risk of developing cancer including breast cancer. Thus, we investigated the associations between the use of statin and the risk of tumor recurrence among breast cancer patients without any evidence of disease. Methods: We reviewed the medical records of female patients diagnosed with stage II/III breast cancer in Albert Einstein Medical Center between 1999 and 2005 and later reached no evident disease (NED) stage after curative therapy. Mean and maximum follow up period were 4.4 years and 9.8 years, respectively. Age, race, family history, smoking history, menopausal status, diabetes, HER2/Neu status, estrogen receptor/progesterone receptor status, TNM stage, tumor size, number of nodes, histology, and treatment received (surgery, radiation therapy, chemotherapy, hormone therapy) were compared between COX-2 inhibitor users and nonusers. The primary and secondary outcomes were disease free survival and overall survival, respectively. Results: Of 707 cancer patients, 19.8% (n = 138) were prescribed statins. 9.4% (13/138) of patients developed recurrence among statin users, while 24.0% (135/563) did among nonusers (odds ratio, 0.33; 95% confidence interval [CI], 0.18-00.; p < 0.001). Variables associated with recurrence in multivariate model were age (adjusted hazard ratio [AHR], 1.03; 95% CI, 1.00-1.06; p = 0.05), TNM stage > II (AHR, 1.24; 95% CI, 1.00-1.53; p = 0.05), number of nodes ≥ 3 (AHR, 2.10; 95% CI, 1.15-3.82; p = 0.02), hormone therapy (AHR, 0.51; 95% CI, 0.32-0.80; p < 0.01) and statin use (AHR, 0.35; 95% CI; 0.16-0.77; p = 0.01). Kaplan-Meier survival analysis revealed that statin use was related to disease-free survival benefit (log-rank test p < 0.001). 5 year survival was 0.89 for statin users, and 0.75 for non- users. However, statin use was not associated with reduced overall mortality in breast cancer patients (AHR, 0.79; 95% CI: 0.39-1.59; p = 0.51; log- rank test p = 0.19). Conclusions: The use of statin is related to reduced risk of developing recurrence in patients with breast cancer. However, prospective randomized trials are needed to validate this finding. No significant financial relationships to disclose.
Phase II multicenter study of abiraterone acetate (AA) plus prednisone therapy in docetaxel-treated castration-resistant prostate cancer (CRPC) patients (pts): Impact of prior ketoconazole (keto)
Authors: D. C. Danila, J. de Bono, C. J. Ryan, S. Denmeade, M. Smith, M. Taplin, G. Bubley, A. Molina, C. Haqq, H. I. Scher
Journal: Journal of Clinical Oncology (2009)

5048 Background: AA is a potent blocker of CYP17, required for synthesis of testosterone in the testes, adrenals, and prostate tissue. Study objectives included confirming AA antitumor activity and safety in multicenter setting, describing changes in ECOG PS, and comparing keto-naïve pts to keto-exposed pts. Methods: The 58 pts had progressive, metastatic CRPC and had failed hormonal therapy and up to two cytotoxic regimens, including docetaxel. AA (1,000 mg QD) and prednisone (5mg BID) were administered daily, the registration trial regimen. 56/58 pts had available data. Results: Baseline demographics: median age - 69.0 (44–86) yrs; median PSA - 151.00 (10.0–3846.0) ng/mL; ECOG 0 (n = 23), 1 (n = 30), 2 (n = 2), missing (n = 1); median prior hormonal therapies were 4 and chemo 1; 24 pts had prior keto, 32 pts were keto-naïve and 2 pts had no data on keto exposure. 45% pts had total maximal PSA decline ≥50%. Total maximal PSA decline (≥30%, ≥50% and ≥90%) in prior keto vs. keto-naïve pts was observed respectively, in: 10 (42%) vs. 20 (63%) pts; 8 (33%) vs. 17 (53%); 1 (4%) vs. 10 (31%). From 32 pts with ECOG 1 or 2, 16 pts (50%, 95% CI 32–68) improved (PS 1 to 0 in 14 pts, PS 2 to 1 in 1 pt; PS 2 to 0 in 1 pt); 39 pts (64% of total 58 pts) maintained PS. Median time to PSA progression was 169 days (95% CI 82–200): keto-naïve-198 days, prior keto-99 days. The majority of AA-related adverse events (AEs) were grade 1–2. No AA-related grade 4 AE was noted. Conclusions: Abiraterone acetate was well-tolerated and produced anti-tumor activity in heavily pretreated pts, as evidenced by PSA declines and improved PS. Incidence of mineralocorticoid-related AEs (HTN or hypokalemia) was reduced with the addition of low-dose prednisone. The keto-naïve post-docetaxel CRPC population was selected for the ongoing phase III pivotal study to confirm these results. [Table: see text]
Relationship between tumor blood flow and serum albumin levels: A positron emission tomography study
Authors: B. Koetz, J. Bruce, P. Price
Journal: Journal of Clinical Oncology (2006)

3058 Background: Positron emission tomography (PET) is increasingly used to aid development of drugs targeting the tumor vasculature. Reduced serum albumin levels lead to a decrease in plasma colloid osmotic pressure, reducing the effective intravascular volume. This study examined the relationship between serum albumin levels and tumor perfusion parameters evaluated with PET. Method: PET perfusion studies using oxygen-15-labeled water (H 2 15 O) were performed as part of clinical trials in 18 patients with advanced solid tumors. Regional tumor blood flow (ml blood /min/ml tissue ) and volume of distribution of water (Vd water ;ml/ml tissue ), an indicator of the fraction of tissue participating in the exchange of water, were measured prior to any intervention and related to serum albumin levels. Two-tailed Pearson’s correlation coefficient was used for statistical analysis. Results: Serum albumin levels ranged from 19 to 44g/l (median 32g/l). Regions of interest were drawn in 7 renal cell cancers, 5 liver metastases, 2 hepatomas, 2 para-aortic lymph node metastases, one mesenteric and one pelvic mass. Tumor blood flow ranged from 0.13 to 1.67ml blood /min/ml tissue (median 0.47ml blood /min/ml tissue ) and tumor Vd water from 0.39 to 1.11ml/ml tissue (median 0.69ml/ml tissue ). A significant correlation between serum albumin level and tumor blood flow (r=0.51, P=.031) could be demonstrated, whereas Vd water was independent of albumin levels (r=0.29, P=.21). Conclusions: This study demonstrates that tumour blood flow is related to serum albumin levels. Changes in serum albumin levels need to be considered when assessing effects on tumor blood flow with treatments targeting the tumor vasculature, particular if given over several weeks. The fraction of perfused tissue may more accurately assess the vascular effects of cancer treatments. If correction of serum albumin levels could be used for therapeutic benefit will require further research. No significant financial relationships to disclose.
Erythrocyte macrocytosis is a rather common, apparently uneventful yet unexplained finding in GIST imatinib (I) chronic therapy
Authors: S. Aliberti, G. Grignani, P. Allione, R. Vormola, A. S. Bucci, G. Porrino, A. Ricchiardi, F. Carnevale Schianca, D. Rota Scalabrini, M. Aglietta
Journal: Journal of Clinical Oncology (2005)

9045 Background: Anemia is an adverse effect related to I therapy both in chronic myeloid leukaemia and in GISTs. Since bone marrow function can be assumed to be unimpaired in GISTs, other anemia causes should be taken in account: 1) gastrointestinal loss (both iron and blood), 2) nutritional deficit (vitamin B12 and folate) and 3) drug assumption. Since we observed an increase in erythrocyte mean corpuscular volume (MCV) during I therapy, we investigated incidence and possible causes of this phenomenon in our prospectively collected series. Methods: Since January 2002 35 consecutive patients affected by advanced GISTs were treated with I starting at 400 mg once a day to be increased to twice a day in case of progressive disease. Laboratory tests were collected before treatment and regularly thereafter with a monthly basis. Only patients with a six month or longer follow-up were included into the analysis. Results: Before therapy hemoglobin (Hb) was lower than 120 g/l in 7/33 (21%) pts (a G0 toxicity according to Common Toxicity Criteria 3.0). Two pts had beta-thalassemia trait (MCV lower than 70 fl). White-cell and platelet counts were in the normal range. During I therapy we observed in 1/33 (3%) pts a G1 anemia, but 5 pts experienced a 20 g/l decrease in Hb (G0). Most notable in 14/33 (42%) an increased MCV was observed always beyond upper normal value (98 fl). Erythrocyte macrocytosis could not be explained on either vitamin deficit base (vitamin B12 and folate within the normal value) or GIST site of origin (gastric vs. enteric). Conclusions: Although anemia requiring I interruption is a rare event, a progressive MCV increase seems to be a rather common side effect of this chronic therapy. To date, the functional level at which imatinib exerts its antiproliferative effect on normal hematopoietic stem cell has not been clarified (Bortolovic K, Blood 2004;103:523). Therefore, we suggest to monitor this “asymptomatic” toxicity adding vitamin supplements without stopping imatinib. No significant financial relationships to disclose.
Conditional survival for intrahepatic cholangiocarcinoma: SEER database analysis.
Authors: Mahvish Muzaffar, Sandeep Kaur, Fir Afroz, Maqbool Lone, Nazir Ahmad Khan, MA Teli
Journal: Journal of Clinical Oncology (2014)

201 Background: Conditional survival can be useful for estimating survival probability for patients who have survived one or more years after the initial diagnosis. It reflects the possible change in risk profile over time especially for malignancies with poor outcome. Methods: The Surveillance, Epidemiology and End Results database was reviewed for intrahepatic cholangiocarcinoma. We reviewed data for all intrahepatic cholangiocarcinoma from year 2000-2010. Data of 8278 patients was extracted from SEER database. We sub stratified using factors like age &lt;50 versus ≥50, gender, grade, stage, primary site surgery. SEER*Stat: Version *8.1.2 software was used to calculate conditional survival. Conditional survival is defined as the calculated probability of survival after having already survived a specified number of years from diagnosis. Results: The analysis showed that Conditional survival (CS) probability for intrahepatic cholangiocarcinoma increased from 33.25 to 85% at 5 years for all age groups conditional to surviving one year after diagnoses. For age group &lt;50 years CS increased from 50.4% to 86.9%, while for age group &gt;50yrs from 31.4% to 84.5%.The conditional survival for well differentiated histology increased from 60.7% to 81.0%, moderately differentiated from 53.8% to 87.7%, poorly differentiated from 37.1% to 83.6% .The conditional survival for localized stage increased from 50.7% to 88.8%, regional 40.6% to 77.7% and distant 19.0% to 65.6%.Majority of cases had missing data with regard to primary site surgery. 1707 cases had documented primary site surgery. Conditional survival for this group increased from 30.7% to 82.8% subject to surviving one year after diagnosis. Conclusions: There are several limitations associated with these results due to missing data in SEER. Nonetheless these results emphasize the trend of patient’s surviving more than 1 year after diagnosis have higher conditional survival probability. CS may provide more relevant prognostic information as compared to traditional survival estimates.
Effect of pan-inhibitory somatostatin analogues, topotecan and bortezomib on the human enterochromaffin neoplastic cell line KRJ-I
Authors: M. Kidd, G. Eick, R. Pfragner, J. Murren, M. Culler, I. M. Modlin
Journal: Journal of Clinical Oncology (2006)

13144 Background: Effective therapeutic options to inhibit the growth and limit the spread of carcinoid tumors are limited. Somatostatin (SST) analogs that target specific SST receptors, though often effective at alleviating the symptoms of carcinoid disease, have limited cytostatic effects on carcinoid tumor cells. The anti-proliferative activity of 2 pan-inhibitory SST analogues and lanreotide were evaluated using the human small intestinal carcinoid cell line KRJ-I. The effects of novel cytotoxic agents used in Phase II carcinoid clinical trials, topotecan (topoisomerase-I inhibitor) and bortezomib (proteasomal inhibitor), were also measured. Methods: The SST receptor profile of KRJ-1 cells was determined using hybridization to U133A chips and confirmed by real time PCR with Taqman probes for SSTR 1–5 . KRJ-1 cells in serum-free medium were treated with 100 pM to 10 μM of the SST pan inhibitory analogs, BIM-23A719 and BIM-23A779, or lanreotide (BIM-23014C) and 1nM to 1 μM of topotecan or bortezomib for 72 hrs. The 3-(4,5-dimethylthiazole-2 yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to evaluate proliferation which was expressed relative to control cells (no agent added). Results: KRJ-I cells co-express mRNA for SSTR 2 and SSTR 3 (mean levels ± SEM 0.48 ± 0.13 and 0.73 ± 0.19 copy/copy GAPDH respectively). BIM-23A719 inhibited growth maximally (15 ± 2% of control) at IC max = 10 pM, whereas BIM-23A779 inhibited growth maximally (11 ± 1% of control) at 100 pM. Lanreotide had no significant inhibitory effect on cell growth and resulted in increased MTT conversion at high concentrations (10 μM). Topotecan and bortezomib inhibited growth maximally at 23 ± 1.5%; IC max = 50 nM and 32 ± 1.6%; IC max = 50 nM respectively. Conclusions: Cytotoxic agents are more effective but less sensitive than pan-inhibitory somatostatin analogues for the inhibition of proliferation of the small intestinal carcinoid KRJ-I cell line. The specific SSTR 2/3/5 analogue, lanreotide, had no inhibitory effect on KRJ-I proliferation. These results suggest that the KRJ-I cell line is more sensitive to analogues targeting a pan-somatostatin receptor profile than cytotoxic agents. The former may have potential as adjuvant agents for treatment of GI carcinoid tumors. [Table: see text]
A Case of Pulmonary Squamous Cell Carcinoma Revealed Ground Glass Opacity on Computed Tomography
Authors: Takao Sakaizawa, Akihiko Yoshizawa, Hideki Nishimura, Takaaki Arimura, Nobutaka Kobayashi, Keisuke Ozawa, Shiho Asaka, Kazuo Yoshida, Kazuya Hirai, Noriko Hosaka
Journal: Journal of Thoracic Oncology (2015)
In vivo activity of R1530 (R) alone and in combination with bevacizumab (B) and peginterferon alfa-2a (P) in a renal cell carcinoma (RCC) xenograft model
Authors: B. Higgins, K. Packman, Y. Zhang, H. Char, M. Simcox, K. Kolinsky
Journal: Journal of Clinical Oncology (2009)

e14629 Background: R1530 is a multikinase inhibitor currently in clinical phase I testing. Its inhibitory profile includes several kinases that play critical roles in cancer cell growth and division as well as tumor angiogenesis. These properties translate into a potent cytotoxicity in a wide range of cancer cell lines in vitro and tumor growth inhibition in human tumor xenografts. Preclinical studies were conducted to evaluate the effects of R alone and in combination with B and P in the Caki-1 RCC xenograft model. Methods: We initially evaluated the antitumor activity of optimal dose (OD) and 1/2 OD R alone and with OD B. This was followed up with testing of OD &amp; 1/2 OD P ± OD B, along with triplets of 1/2 OD P + OD B + 1/2 OD R and OD P + OD B + 1/2 OD R. A final study compared 1/2 OD R to OD R triplets to attempt to increase tumor growth inhibition (TGI) and increase life span (ILS). Results: No doublets or triplets tested showed antagonism or enhanced toxicity. Antitumor activity and survival results are listed below (Table). Conclusions: 1/2 OD R + OD B or OD R + OD B doublets gave better TGI and ILS than monotherapy. Comparing these two doublets, TGI is better in the high dose combination but ILS is equivalent. All TGI and ILS are better in doublet P + B combinations over respective single agent arms except for TGI (but not ILS) for 1/2 OD P vs its correlative doublet with B. The OD P + B doublet gave better TGI and ILS than 1/2 OD P + B doublet. TGI and ILS do not differ between triplets containing OD R + 1/2 OD or OD P or for triplets containing the OD P + 1/2 OD or OD R. Therefore, either agent can be alternatively dose reduced without a loss of tumor response or detriment to survival in this preclinical model of RCC. [Table: see text] [Table: see text]
Variation in enrollment of colorectal cancer patients in clinical trials
Authors: R. Joubert, U. Raeth, T. Moehler
Journal: Journal of Clinical Oncology (2009)

e15094 Background: Correct estimation of patient enrollment is an important success factor for planning clinical studies including studies for metastatic colorectal cancer (CRC). Methods: We reviewed all CRC studies published in the Journal of Clinical Oncology and Annals of Oncology between 01/2007 and 10/01/2008. 43 studies were found and the following data were collected from 39 studies: indication, phase, number of sites, number of patients enrolled, mean patient age, recruitment time, sponsor (Industry, NIH, Organization, University), region, line of treatment and type of drug (6 categories). 4 studies were omitted from analysis as recruitment data were largely missing. Our analysis is based on a literature review as information from unpublished trials is unavailable. This implies some limitations regarding the data interpretation. Results: An average enrollment of 0.92 Patient/Site/Month (range 0.10–7.38) was observed for these trials. The highest recruitment efficacy with a median of 4.11 Pt/S/M (range 1.81–7.38) was found in 5 single institution phase II trials. For multi-center phase II and III studies the median enrollment was 1.82 and 0.32 Pt/S/M respectively, with significant higher recruitment in phase II studies. The highest enrollment rate was observed for studies located in Europe or in USA (0.77 and 2.21 Pt/S/M respectively, p=0.03). No correlation was seen with the mechanism of action (targeted drug vs. chemotherapy), sponsor (NIH vs. Industry vs. IIT), line of treatment (first line vs. 2nd and subsequent line). For phase I recruitment analysis we retrieved 2 studies that investigated novel agents in solid tumor patients including advanced or metastatic colorectal cancer patients with a median recruitment of 0.46 Pt/S/M. For phase Ib and I/II recruitment analysis 5 studies were found with a median recruitment of 0.78 Pt/S/M. Conclusions: Single institution phase II clinical trials on novel agents with high potential to change future treatment standard demonstrate almost a tenfold higher than average recruitment rate for multi-center trials (0.45 Pt/S/M). Despite some limitations in the interpretation of results our analysis provides important information to support estimation of patient recruitment in future clinical trials for colorectal cancer. No significant financial relationships to disclose.