tbuckley/cabot-search huggingface dataset:
Phase I/II study of combination chemotherapy with S-1 and cisplatin every 3 week schedule in patients with metastatic or recurrent gastric cancer
Authors: J. Lee, H. Kang, Y. Kang, M. Ryu, H. Chang, T. Kim, H. Sohn, H. Kim, J. Lee
Journal: Journal of Clinical Oncology (2007)

15066 Background: S-1 plus cisplatin has been reported to be highly active in advanced gastric cancer (AGC). The objectives of this study were to define the maximal-tolerated dose (MTD) of S-1, given for 2 weeks separated by 1 week rest, with a fixed dose of cisplatin, and to determine the activity and safety of this combination regimen at the recommended dose (RD) when used as the first line treatment of AGC. Methods: Cisplatin was fixed at a dose of 60 mg/m 2 on D1 and the starting dose of S-1 was 30 mg/m 2 bid (level I) on D1 to D14 every 3 weeks. The dose of S-1 was increased by 5 mg/m 2 bid up to 50 mg/m 2 bid (level V) unless MTD was achieved. At every level, a cohort of 3 patients (pts), which could be expanded to 6 pts, was studied. Dose-limiting toxicities (DLTs) were assessed for the first 2 cycles. Results: From February 2004 to January 2006, 62 eligible pts were enrolled. In phase I (N=21), DLTs occurred at level V (S-1 50 mg/m 2 bid), with 2 of 3 pts developing G3 diarrhea or febrile neutropenia. The RD was determined at level IV (45 mg/m 2 bid) because only 1 DLT occurred out of 6 pts at this level. After the first 20 pts (series I) were enrolled in phase II, the protocol was amended; the S-1 dose was reduced down to 40 mg/m 2 bid (level III, series II, N=23) because of poor bone marrow recovery and resultant treatment delay. At the time of analysis, a total of 272 cycles of chemotherapy were administered. The median age was 52 years (28–70) and ECOG PS was 0/1 in 98% of pts. The objective response was observed in 20(47%; 95% CI, 36–66%) of 43 pts. SD was achieved in 15 (35%) pts. With a median FU of 12.1 months (range 9.8–23.3) for all survivors, median PFS was 5.3 months (95% CI, 4.6–6.0 months) with a median OS of 10.0 months (95% CI, 5.1–14.8 months). G3–4 toxicities included neutropenia (33%), anemia (31%), anorexia (24%), and asthenia (14%); however severe febrile neutropenia, abdominal pain, and stomatitis were never observed. Conclusions: The cisplatin plus S-1 regimen incorporating 2-weeks on and 1-week off is highly active against gastric adenocarcinoma with favorable toxicitiy profiles in Korean patients. No significant financial relationships to disclose.
Impact of reduced dose intensity of adjuvant anthracycline based chemotherapy in a population based cohort of stage I-II breast cancers
Authors: A. Tinker, C. Speers, J. Barnett, I. Olivotto, S. Chia
Journal: Journal of Clinical Oncology (2004)

552 Background: Reductions in the dose intensity (DI) of adjuvant doxorubicin and cyclophosphamide (AC) chemotherapy in the treatment of early stage breast cancer are frequently required, with the impact on clinical outcome uncertain. We examined whether a reduced DI had an impact on relapse free survival (RFS), breast cancer specific survival (BCSS) or overall survival (OS) in a population-based cohort of early stage breast cancers treated with adjuvant AC. Methods: Women with stage I/II breast cancer treated with adjuvant AC (A: 60 mg/m2, C: 600 mg/m2 on a 21-day schedule) between 1990 and 1995 were retrospectively identified through the BCCA pharmacy database and linked to the BCCA Breast Cancer Outcomes Unit database. A dose reduction was defined as a reduction of at least one of the chemotherapy agents by at least 25% in any given cycle. Dose delay was defined as a delay in delivering treatment by at least 5 days. Cases were classified into the following 4 cohorts; cohort 1: entire course of treatment delivered at full doses and on time; cohort 2: one single dose reduction or dose delay; cohort 3: more than one dose reduction or dose delay; cohort 4: = 2 cycles of chemotherapy delivered. No growth factor support was utilized in any cases. Results: 484 cases were retrospectively identified (cohort 1: n = 268; cohort 2: n= 88; cohort 3: n= 89; cohort 4: n= 39) with a median follow-up of 9.6 years. The four cohorts were well matched for most baseline prognostic factors except for slight imbalances in lymph node status (p=0.05) and adjuvant hormonal therapy (p=0.05). 55% of the entire cohort had node positive disease. Overall 45% of cases had a reduced DI delivered. However, there were no significant differences in 8 year RFS (p=0.94), BCSS (p=0.87) and OS (p=0.86) between the 4 cohorts. The 8 year outcomes for cohorts 1–4 respectively were: RFS (72%, 74%, 74%, 68%), BCSS (80%, 77%, 82%, 80%) and OS (78%, 76%, 80%, 77%). Conclusions: Although reductions in the DI of adjuvant AC chemotherapy for early stage breast cancer was common, it did not appear to significantly impact on clinical outcomes in this cohort of patients with stage I-II breast cancer. No significant financial relationships to disclose.
Erlotinib versus chemotherapy (CT) in advanced non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations: Interim results of the European Erlotinib Versus Chemotherapy (EURTAC) phase III randomized trial.
Authors: R. Rosell, R. Gervais, A. Vergnenegre, B. Massuti, E. Felip, F. Cardenal, R. Garcia Gomez, C. Pallares, J. M. Sanchez, R. Porta, M. Cobo, M. Di Seri, P. Garrido Lopez, A. Insa, F. De Marinis, R. Corre, M. Carreras, E. Carcereny, M. Taron, L. G. Paz-Ares
Journal: Journal of Clinical Oncology (2011)

7503 Background: EGFR tyrosine kinase activating mutations are present in 10-26% of NSCLC tumors and are associated with increased response to gefitinib and erlotinib. However, little is known about how the efficacy and safety profile of erlotinib compares with CT in EGFR-mutant Caucasian p. We have performed a prospective, randomized phase III study comparing erlotinib with platinum-based CT in chemonaive advanced NSCLC p with EGFR mutations. Methods: From February 2007 to January 2011, we screened 1,227 p for EGFR mutations, and 174 patients were randomly assigned to receive erlotinib or platinum-based CT. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response, overall survival and toxicity profiles. Results: 153 p (76 CT, 77 erlotinib) are evaluable for the interim analysis. p characteristics CT arm: 16 males; median age, 64; never smokers, 56; PS 0, 26; PS 1, 41; adenocarcinoma, 67. p characteristics erlotinib arm: 25 males; median age, 65; never smokers, 54; PS 0, 23; PS 1, 44; adenocarcinoma, 73. Preliminary results of the interim analysis are now available. Response rate was 10.5% to CT vs 54.5% to erlotinib (P<0.0001). PFS in the CT arm was 5.2 months (m) (95%CI, 4.4-5.8 m) compared to 9.4 m (95%CI, 7.9-12.3) in the erlotinib arm (HR, 0.42; P<0.0001). Median survival was 18.8 m in the CT arm and 22.9 m in the erlotinib arm (HR, 0.80; P=0.42). Most common toxicities were asthenia (68.9%), anemia (45.9%), nausea (40.5%) and neutropenia (36.5%) in the CT arm, and diarrhea (57.3%), asthenia (53.3%), and rash (49.3%) in the erlotinib arm. Final results of the interim analysis will be presented. Conclusions: The EURTAC study met its primary endpoint at the interim analysis. Erlotinib as first-line treatment for advanced NSCLC p with EGFR mutations improves PFS, with acceptable toxicity, compared to platinum-based chemotherapy.
A phase II trial of ZD 1869 for advanced cutaneous squamous cell carcinoma of the head and neck
Authors: R. S. Weber, R. Lustig, B. Glisson, D. Rosenthal, E. Kim, A. El-Naggar, A. Chalian, E. Hanna
Journal: Journal of Clinical Oncology (2007)

6038 Background: Advanced HN CSSC carries a 30–40% risk of death by 2 years with standard therapies. A number of patients (pts) with clinically aggressive CSCC tend to have a poor prognosis when treated with standard approaches using surgery and radiation (RT), thus novel therapies are needed. CSSC over expresses the epidermal growth factor receptor (EGFR) and these compounds have activity in head and neck cancers. We are studying the use of gefitinib as an induction therapy in a high-risk patient group prior to definitive therapy to determine the overall efficacy, toxicity and feasibility. Methods: Eligible pts must have HN CSSC &gt;2cm, regional nodal metastases, peri-neural invasion, or deep invasion into cartilage, muscle or bone and must be candidates for definitive local-regional therapy with surgery and/or radiation. Two 30-day cycles of gefitinib 250mg administered orally are given daily prior to definitive therapy. Pts are assessed clinically after the first 30-day cycle. If a response is noted, gefitinib is continued. For patients with stable disease, the dose is escalated to 500mg daily. Pts with progressive disease go off study. Biomarker evaluations including EGFR and Akt expression prior to and after induction are planned. Results: To date, 14 pts have been enrolled. 10 are evaluable for response and 13 for toxicity. A complete clinical response (CR) was noted in 3 pts (30%, one pathological CR), partial response in 2 patients (20%), stable disease in 2 (20%) and progressive disease in 3 (30%). Therapy was well tolerated with 2 patients having grade 3 toxicity (rash, diarrhea, or elevated liver enzymes). Conclusions: Standard definitive surgery and RT are inadequate for patients with advanced HN CSSC. The emergence of targeted therapies has given new hope for many patients with high-risk cancers. The preliminary results from our study suggest that gefitinib is an active agent for HN CSCC, and is well tolerated. Correlative studies may help identify patients most likely to respond to anti- EGFR therapy. [Table: see text]
Receiving a cancer diagnosis: Interview of random and not ill population.
Authors: Bruno Henrique Rala De Paula, Eduardo Camargo Millen, Rodrigo Almeida, Fernando C. O. Almeida
Journal: Journal of Clinical Oncology (2014)

235 Background: In clinical practice the way you communicate a diagnosis is very important, especially because the reaction of patients is unexpected. Studies performed in order to check for trends or predictors that news produces no harmful effects and possibly to generate further patient adherence. However studies are focused on evaluate sick patients or their family members, referring to the need to evaluate a random population which is the distribution of opinions as the patient arrives at the doctor's office. Methods: Were interviewed 1,191 people randomly by medical students, on the streets of Volta Redonda city, RJ, between January and December 2010 after the exclusion criteria were tabulated 1,181 questionnaires. Results: 8.13% of responders would not like to be told that they had cancer. 27.51% believe that there is a reason not to tell the patient the diagnosis, and the reasons were: 40% psychological effects ; very committed clinical status 18.46%, embarrassment or discrimination 12.92%; mercy 9.23% and other opinions 19.38%. Cases of cancer in family were 48.01% and 74.11% of those the patient was not informed and the relative judged important the patient knowledge about their condition. Predominance of the way we should tell the patient his diagnosis according to the responders was 41.06% (patient, family and doctor in a moment), 29.46% (only doctor and patient) and 24.80% (the family knowing the diagnosis informing your loved sick in a second time). When asked if they should start cancer treatment before telling the patient to 8.89% of respondents said yes. And 68.57% of people believe to be beneficial to start treatment before telling the patient his diagnosis, said they think their next of kin should be informed that he has cancer. Conclusions: Receiving a cancer diagnosis is not easy for some individuals. Depending on who has cancer, person or a relative, some individuals are more likely to dissent opinion on whether to inform or not the diagnosis. There was a tendency to prefer the diagnosis is communicated by the doctor to the patient with family present. Finally there might be a correlation between the respondents believe that it is important to start treatment before giving the diagnosis to a relative.
A phase II feasibility study of sorafenib and gemcitabine combination therapy in advanced hepatocellular carcinoma.
Authors: N. Naqi, S. Ahmad, S. Murad, J. Khattak
Journal: Journal of Clinical Oncology (2011)

298 Background: Sorafenib is considered standard of care in advanced hepatocellular carcinoma (HCC) giving survival benefit of around 4 months. Its combination with gemcitabine, a pyrimidine analogue with limited friendly hepatic profile, may improve results. The primary objective of this study was to evaluate the efficacy and safety of sorafenib and gemcitabine combination in advanced HCC. Methods: 30 patients of advanced HCC were enrolled in this non-randomized, open-label treatment protocol. Sorafenib 400 mg orally twice daily with gemcitabine 1,000mg/m 2 intravenous on day 1 and 8 of a 4 week cycle for 4 months. Inclusion criteria: Child class A and B, adequate liver, marrow and renal functions, at least one uni-dimensional measureable lesion, Exclusion criteria: uncontrolled hypertension, serious infections, brain metastasis, bleeding diathesis, pregnant or lactating. National Cancer Institute criteria for adverse events (NCI CTCAE) Version 3.0, and Response evaluation criteria for solid tumors (RECIST) was used for assessment. Results: 30 patients: 23 male and 7 female. 24 (80%) Child class A and 6 (20%) class B. All had chronic liver disease. 22 (73.3%) had significantly high alfa-fetoprotein levels (≥ 500). 20 (66.7%) positive for hepatitis C, 4 (13.3%) for hepatitis B. 6 (20%) had no evidence of viral infection. 19 (63.3%) had multifocal lesions and 11 (36.7%) unifocal. 18 (60%) completing 4 cycles of treatment were assessed for response. 2 partial responses (PR) and 8 stable disease (SD) were seen. No complete response (CR) was observed. 8 patients had progressive disease, 4 progressing on interim assessment were taken off protocol. Toxicity: primarily hematological. Gemcitabine related thrombocytopenia being the most common (40%) requiring frequent dose modifications and delays. Sorafenib specific, hand foot skin reaction and anorexia were next most frequent. Conclusions: Sorafenib and gemcitabine combination is not feasible in advanced HCC due to its hematological toxicity especially thrombocytopenia, requiring frequent dose reductions and delays. No significant financial relationships to disclose.
Phase I study of imatinib mesylate and gemcitabine in patients with refractory solid tumor malignancy
Authors: E. Poplin, M. Gharibo, L. Rodriquez, Y. Elsayed, M. Wojtowicz, M. Gounder, T. Lagattuta, E. Rubin, M. Egorin
Journal: Journal of Clinical Oncology (2005)

3100 Background: Based on the preclinical activity of Gemcitabine (Gem) and imatinib mesylate (IM) (Gleevec) in combination (R. Hwang et al, 2003), a phase I study of Gem+IM was developed to determine MTDs for both Gem and IM when administered in combination. The study also assesses Gem PK in the presence and absence of IM. Methods: Patients (pts) with refractory malignancy; intact intestinal absorption, measurable/evaluable disease, adequate hepatic, renal and hematologic function; PS 0–2 and survival time > 3 months who signed informed consent were eligible. Pts were treated at 10 dose levels. Gem, administered by fixed dose rate infusion, 10 mg/m2/min, had an initial schedule of 600 mg/m2 d1,8,15 q28d. Dose was decreased due to toxicity to 450 mg/m2/ d 3,10 q 21d and, subsequently, re- escalated to 1000 mg/m2 d 3,10 q21 days. IM dose started at 300 mg qd, was deescalated to 300 mg, d1–5 and 8–12 and escalated to 400 mg/d 1–5 and 8–12 q21d. Results: 24 men and 10 women, median age 62 (range 28–83) received treatment. Tumor types were NSCLC(9), pancreas (8),renal(4), other(14). Daily dosing with IM and Gem 500–600 mg/m2/d1,8,15 yielded gr 3 ALT, gr 3 dysesthesia, gr 3 neutropenia, and gr 3 refractory nausea/ vomiting. Intermittent dosing of IM d1–5 and 8–12 and Gem d 3,10 was better tolerated with rare gr3 toxicity and no DLT through the current level of Gem 1000 mg/m2 and IM 400 mg. Partial and minor responses, respectively were noted in laryngeal and renal cancer at Gem doses of 450 mg/m2 and 500 mg/m2. Stable disease >6 months was seen in 6 pts. 4/4 pancreatic ca pts with initial elevated CA19–9 had 88–90% reduction. IM does not significantly alter Gem PK. Conclusion: The addition of IM to Gem, even at low dose, may augment the activity and range of Gem. (Supported by Novartis) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly, Novartis Eli Lilly, Novartis
Assessing the impact on morbidity and mortality of neoadjuvant chemotherapy in patients with high-risk and muscle invasive bladder cancer eligible for radical cystectomy.
Authors: Ettore Di Trapani, Rafael Sanchez-Salas, Lorenzo Rocchini, Giorgio Gandaglia, Marco Moschini, Daphne Lizee, Eric Barret, Francois Rozet, Marc Galiano, Renzo Colombo, Alberto Briganti, Francesco Montorsi, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2015)

331 Background: Despite the increasing number of studies confirming the importance of neoadjuvant chemotherapy in patients addressed to radical cystectomy (RC) for bladder cancer (BC), its association remains controversial. We aimed to test the safety and the efficacy of neoadjuvant chemotherapy in pts underwent RC for BC in a multistitutional retrospective study Methods: We analyzed 768 pts who underwent RC and PLND with / without neoadjuvant chemotherapy in two European high volume centers between 2007 and 2013. Complete demographic, pre and postoperative functional data and oncologic outcomes were collected. T-tests and Chi-square analyses were used to evaluate the differences between the groups. Kaplan-Meier curves were used to assess time to cancer specific mortality (CSM) free and overall mortality (OM) free survival. Univariable (UVA) and multivariable (MVA) logistic and Cox regression analyses were developed to address predictors of perioperative complications and CSM- and OM-free survival. Results: The mean follow up was 20 months (range 1-24). Mean age at surgery was 67 yrs (median 67 yrs). Patients had mainly pT2 disease (79,6%). Overall, 14% of pts had preoperative cisplatinum based neoadjuvant chemotherapy. We did not find any difference in pre-operative and post-operative blood tests assessment (all p&gt;0.1). Intraoperative blood loss was higher in patients who went directly to surgery (mean 1.200 vs 740 cc; p&lt;0.001) but the number of transfusions was similar (p=0.77) as well as the hospital stay (p=0.8). The complication rate was not significant at the MVA logistic regression analysis (p=0.74) even after evaluating per Clavien-Dindo groups (p=0.11). Neoadjuvant chemotherapy showed a better CSM-free survival at UVA (p=0.035) and at MVA (p= 0.043; OR 0.44). Then a nomogram was developed to predict the 60 months CSM-free rate showing an accuracy of 72.6%. Conclusions: Neoadjuvant chemotherapy is associated with a better CSM-free survival in patients with high-risk bladder cancer eligible for RC and it’s not linked with perioperative morbidity. We finally developed the first nomogram predicting the CSM-free rate in these patients.
Histology- and gender-related associations of ERCC1, RRM1, and TS biomarkers in 1,802 patients with NSCLC: Implications for therapy.
Authors: D. R. Gandara, P. P. Grimminger, P. C. Mack, P. V. Danenberg, P. Lara, K. D. Danenberg
Journal: Journal of Clinical Oncology (2010)

7513 Background: Histology-based decision making for non-small cell lung cancer (NSCLC) has recently been advocated. We hypothesized histology- and gender-related associations for purported chemotherapy predictive biomarkers: ERCC1 (platinum), RRM1 (gemcitabine), thymidylate synthase or TS (pemetrexed). We report analysis of the Response Genetics (RGI) database and implications for therapy. Methods: RNA from microdissected formalin-fixed paraffin-embedded tumors was analyzed as previously described, reported as the ratio of gene expression to β-actin. For reference, median ERCC1 levels <1.7, RRM1 <0.97 and TS <2.33 are reported to correlate with improved response. Results: Specimens from 1,802 individual NSCLC patients were analyzed for 1 or more biomarkers. For each biomarker, gene expression is higher in SCCA compared with AC (<0.001*), including RRM1, a reported biomarker for gemcitabine. There is no association of gene expression with age or stage. Gene expression is higher in males vs females: ERCC1: 2.51 vs 2.22 p=0.005; RRM1: 1.41 vs 1.24 p=0.004; TS: 3.23 vs 2.83, p<0.001*. However, SCCA is more frequent in males vs females (30%/19%, p<0.001, Fischer exact test). When AC and SCCA are assessed separately, statistical significance between gene expression and gender is lost (in SCCA: ERCC1 p=0.14; RRM1 p=0.26; TS p=0.11). Conclusions: 1) This analysis represents the largest dataset of these biomarkers yet reported. 2) While significant histology-related associations for ERCC1, RRM1 and TS are seen, marked heterogeneity exists in individual patient expression levels. 3) Gender-related associations suggesting enhanced chemotherapy sensitivity in females are partly histology-related. 4) Biomarker assessment in individual NSCLC patients may optimize histology-based decision making. Biomarker NSCLC-Total N = 1,802 NSCLC-Squamous(SCCA) N = 392 NSCLC-Adenoca(AC) N = 920 SCCA vs. AC P value ERCC1 N 1,593 371 786 <0.001* Median 2.14 2.6 1.93 Range 0.04-24.79 0.27-14.34 0.04-24.79 RRM1 N 925 189 501 <0.001* Median 1.3 2.84 1.09 Range 0.25-33.19 0.56-33.19 0.25-10.93 TS N 1,014 264 500 <0.001* Median 2.92 4.31 2.5 Range 0.14-60.58 0.14-59.16 0.39-30.33 * Mann-Whitney test. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb/Imclone, Genentech, GlaxoSmithKline, Lilly, Merck, Novartis, Pfizer, Response Genetics, sanofi-aventis Response Genetics Response Genetics Abbott Laboratories, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, Pfizer