tbuckley/cabot-search huggingface dataset:
Single-agent chemotherapy trials in small-cell lung cancer, 1970 to 1990: the case for studies in previously treated patients.
Authors: S C Grant, R J Gralla, M G Kris, J Orazem, E A Kitsis
Journal: Journal of Clinical Oncology (1992)

PURPOSE This review was undertaken (1) to determine the antitumor activity of agents studied in phase II trials in small-cell lung cancer (SCLC) patients, (2) to evaluate the adequacy of published trials, (3) to determine if previously treated patients are suitable for phase II trials in SCLC, and (4) to develop an improved design for phase II trials. DESIGN English-language, single-agent efficacy trials in SCLC, published from 1970 to 1990, were reviewed. Study design and reporting of results were assessed for clinical and statistical methodology. Response rates observed in previously treated patients were compared with those observed in previously untreated patients. RESULTS One hundred forty-one articles evaluating 57 agents in 3,042 patients were reviewed. Eleven drugs were active (defined as a response rate greater than or equal to 20% in a trial with greater than or equal to 14 assessable patients), and 12 were inactive. Due to methodologic problems with the clinical trials, the usefulness of the remaining 34 drugs (60%) remains uncertain. Deficiencies identified in trials include inappropriate sample sizes, poorly defined response criteria, and failure to report important prognostic factors. When studied in adequate trials, all agents known to be active in SCLC had an observed response rate greater than or equal to 10% in previously treated patients. CONCLUSIONS Over the past 2 decades, phase II trials in SCLC have failed in their primary task of effectively identifying agents that warrant further clinical study and rejecting inactive agents. If only previously treated patients had been entered into these trials, no useful agent would have been missed provided that a lower observed response rate had been used as evidence of antitumor activity. We propose a two-stage sequential study design, entering previously treated patients, for future phase II trials in SCLC.
A phase II study of erlotinib (E) in previously untreated elderly patients (pts) with inoperable or advanced stage non-small cell lung cancer (NSCLC) cancer and an ECOG PS 0–3
Authors: L. Rajdev, F. Camacho, C. Hall, U. Hopkins, R. Gucalp, R. Perez-Soler
Journal: Journal of Clinical Oncology (2008)

19098 Background: Co-morbid conditions and concern for tolerability may preclude the use of chemotherapy (CT) in elderly pts. Given the manageable toxicity and demonstrated efficacy of E in pts who have received prior CT, we conducted a phase II study of E to evaluate the disease control rate and toxicity in previously untreated elderly pts (age>65 y) with advanced and inoperable NSCLC. Methods: Pts with NSCLC who are inoperable and/or unable to tolerate definitive CT/RT, stage IIIB/IV; no prior chemotherapy/biologic therapy for NSCLC; measurable disease; PS 0–3. Treatment: E 150 mg orally daily for the first 14 day, escalated to 200 mg daily on day 15 if there is no evidence of ≥ grade 2 non-hematological toxicity. Results: 30 pts were treated; 28 evaluable for response; M/F: 13/17; Median age is 78.2 y; range (65.0–92.5 y); PS 0/1/2/3:1/20/5/4; Path: adeno 43%; current/former smoker 63%. Treatment was well tolerated. Toxicity: rash 24 pts 80%, diarrhea 13 pts 43%, ocular 6 pts 20%. Other ≥ grade 3 toxicities: dyspnea, fatigue, anorexia and dehydration, each 1 pt (3.3%). 8/30 (26.6%) were dose reduced. Response: CR: 0; PR: 3; (10%; 95% CI 4.18, 17.2); SD: 9 (30%; 95% CI 16.4, 48.3), PD 16 (53%) and overall disease control rate 40%. 3/3 (100%) PRs and 7/9 (77.7%) SD were observed in smokers. Median duration of response and stable disease: 10.4 month (mth) (range 8.16–12.52+) and 5.29 mths (range 1.52- 18.33). Overall median survival time 5.57 mths; (95% CI 3.52, ∞), PS ≤ 1 median survival time 11.7 mths, (95% CI 5.49, ∞), PS > 1, median survival time 1.77 mths, (95% CI 1.02, ∞). 12 mth median survival rate 35.9%, (95% CI 22, 58.3). Conclusions: E appears to be well tolerated and demonstrates modest activity in patients ≥ 65 years of age with previously untreated advanced NSCLC. In addition, the results suggest that in this patient population E clinical benefit may not be mostly observed in non-smokers. Monotherapy with E may be considered as a frontline therapeutic option in elderly patients unable to tolerate chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology
Prognostic value of the most frequent mutations in GIST: Results of the French population-based prospective study MolecGIST.
Authors: J. Emile, S. Brahimi, J. Coindre, J. Blay, P. Aegerter, J. Scoazec, G. Viennet, O. Bouche, L. Doucet, A. Wacrenier
Journal: Journal of Clinical Oncology (2010)

10034 Background: More than 80% of gastrointestinal stromal tumors (GIST) have KIT or PDGFRA mutations, of which more than 100 different types have been published. Several studies have investigated the prognostic value of these mutations, however most were retrospective and mixed several mutations together. We investigated the prognostic value of the most frequent mutations. Methods: Patients with GIST were prospectively included in MolecGIST study (#A10535, ASCO 2009). We selected the 9 most frequent mutations, and a 10th group of patients with a deletion within PDGFRA exon 18 (18del). These patients accounted for 45% of those for which mutations were available. Results: The 9 most frequent mutations were KIT AY502- 503dup (n=26), V559D (n=25), 557-558del (n=23), W557R (n=14), V560D (n=13), L576P (n=11), V559G (n=7), 560del (n=6), and PDGFRA D842V (n=30). 18del group included 17 patients. Metastases were present at diagnosis in 20 (12%) patients. Evolution after surgical resection was available for 138 other patients, with a median follow up of 2.3 months. 58% of the patients had intermediate or high Fetcher's risk, and 30 of them received Imatinib as adjuvant treatment. GIST recurrence occurred in 12 patients. The 3 relapsing patients of the adjuvant group had AY502-503dup (n=2) and W557R. The 9 others had AY502-503dup (n=2), V559D (n=1), 557-558del (n=1), L576P (n=1), V559G (n=1), D842V (n=1) and 18del (n=2). GIST malignancy (metastasis or relapse) was associated with the type of mutation (p=0.024, Fisher's exact test). Mutations AY502-503dup, 557-558del, V559G and 18del were of high risk (33% malignant), D842V, V559D, L576P, W557R were of low risk (10% malignant), and those involving V560 were of very low risk (0/17 malignant). Conclusions: The precise type of KIT and PDGFRA mutations is predictive of malignancy in GIST, and mutations involving adjacent amino acid may have very different prognostic value. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Pfizer Novartis, Pfizer Novartis Novartis
Phase I studies of CBP501, a novel G2 checkpoint abrogator, alone and combined with cisplatin (CDDP) in advanced solid tumor patients (pts)
Authors: B. Y. Wong, G. I. Shapiro, M. S. Gordon, M. J. Borad, J. P. Eder, R. Tibes, D. S. Mendelson, E. Wasserman, T. Kawabe, S. Sharma
Journal: Journal of Clinical Oncology (2008)

2528 Background: Most cancer cells are dependent on the G2 checkpoint to survive with DNA damage. The stable peptide CBP501 shows selective G2 checkpoint abrogation, with activity in various tumor models, alone and combined with DNA damaging agents. CBP501 was evaluated in 2 phase I studies, single agent and with CDDP, determining maximum tolerated dose (MTD), dose limiting toxicity (DLT), safety and PK. Methods: CBP501 was given over 1 hr, via central catheter, with prophylactic anti-allergics due to histamine release syndrome in animals. PK was examined in cycle (cy) 1. MTD is the level below that where 2 of 3–6 pts have DLT during cy 1–2. Study A: CBP501 day 1/8/15, q4w, initial dose 0.9 mg/m². Study B: q3w, initial CBP501/CDDP doses 3.6/50 mg/m². Results: Studies were run in 4 US centers from Jun-05 to Dec-07. A) 30 pts treated, M/F: 16/14, median age 61 (25–82), PS 0/1/2: 9/20/1, median 4 prior lines, colon (5 pts), pancreas/biliary (6), ovarian (6), melanoma (2), renal (2), NSCLC (2), other (7). Median cy/pt: 2 (1–8). All pts discontinued due to PD. 1 DLT occurred (transient asymptomatic G3 troponin elevation) at 22.5 mg/m² (top DL given). No other G3–4 adverse events (AEs) occurred; 13 pts (43%) had G1–2 allergy. MTD was not reached. 2 pts (pancreas, ovarian) had SD for 7 cy. B) 27 pts treated, M/F: 14/13, median age 61 (31–81), PS 0/1: 8/19, median 4 prior lines, mesothelioma (5), prostate (4), NSCLC (4), pancreas/biliary (3), esophageal (3), other (8). Two DLTs (G3 allergic reaction) occurred at CBP501/CDDP 36.4/75 mg/m². No other G3–4 AEs occurred. MTD was defined as 25 mg/m² CBP501, 75 mg/m² CDDP. Allergic reaction was the most common AE, observed in 12 (44%) pts. PR (unconfirmed) endometrial (7+ cy, CA125 50% drop); SD, 2 mesothelioma (11+, 5), adenoid cystic (8), neuroendocrine (4+), ovarian (3+, CA125 50% drop), NSCLC (3+). PK: CBP501 Cmax and AUC showed dose-proportionality, and no difference between day 1 and 15 for both studies. Conclusions: CBP501 was well tolerated, as single agent and with CDDP. The main toxicity was dose-limiting allergic reaction. Promising signs of efficacy are seen in pts already exposed to platinum. Phase I-II studies of CBP501/pemetrexed/CDDP are planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology, CanBas Co Ltd CanBas Co Ltd, TGen Clinical Research Services
Concurrent cetuximab, cisplatin, and radiotherapy (RT) for loco-regionally advanced squamous cell carcinoma of the head and neck (SCCHN): Updated results of a novel combined modality paradigm
Authors: Y. B. Su, D. H. Kraus, M. J. Zelefsky, E. Lis, S. L. Wolden, K. Herman, F. Sedarati, A. R. Shaha, J. P. Shah, D. G. Pfister
Journal: Journal of Clinical Oncology (2005)

5529 Background: We previously reported results of a phase 2 study of concurrent cetuximab, a chimeric monoclonal antibody directed against the epidermal growth factor receptor, with cisplatin and RT in previously untreated patients with loco-regionally advanced SCCHN (ASCO 2003 A#1993). Preliminary efficacy data were encouraging, although toxicity was a concern. Subsequent prospective data indicate that cetuximab has significant clinical activity in patients with SCCHN both as a single agent, as well as a potentiator of RT, making the longer-term efficacy data from our prior study of particular interest. Methods: All patients received RT (70 Gy by concomitant boost) with planned concurrent cetuximab (400 mg/m2 IV x1, then 250 mg/m2 weekly during weeks 2–10) and cisplatin (100 mg/m2 IV during weeks 1 and 4). Surgery was reserved for relapsed/persistent disease. Primary endpoint was response rate. Secondary endpoints included toxicity, overall survival, progression-free survival, and quality of life (FACT-HN). Results: Twenty-two patients were enrolled: median age 57 (41–72), median Karnofsky score 90 (70–90), oropharynx 59%, T4 36%, N2/3 77%, Stage IV 86%. Study was closed early due to toxicity, although attribution was unclear: 2 deaths (1 pneumonia, 1 cause unknown), 1 myocardial infarction, 1 bacteremia, 1 atrial fibrillation. Acneiform rash (any grade) occurred in 20 (95%) patients. Of the 16 patients evaluable for response, 15 (94%) had major response (2 CR, 13 PR). Of the 13 patients with PR, 9 have remained disease-free through latest follow-up. With median follow-up of 44 months, and all survivors followed for minimum 31 months, 3-year overall survival is 76% and 3-year PFS 59%. FACT-HN functional and physical quality of life indices decreased at week 6, but returned to baseline at 12–16 week post-treatment follow-up. Conclusions: Efficacy data for this novel combined modality therapy paradigm remain encouraging. Notably, many patients with radiographic PR have remained disease-free long-term. Phase 1 investigations of better tolerated ways of incorporating cetuximab with chemoradiotherapy are indicated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems ImClone Systems ImClone
Non-Hodgkin lymphoma of the Waldeyer's ring: Is a higher radiotherapy dose required?
Authors: G. Bahl, S. Laskar, M. A. Muckaden, R. Nair, S. Gupta, A. Bakshi, S. Gujral, P. M. Parikh, S. K. Shrivastava, K. A. Dinshaw
Journal: Journal of Clinical Oncology (2007)

8067 Background: To evaluate the prognostic factors and treatment outcome of Indian patients with primary Non-Hodgkins Lymphoma (NHL) of the Waldeyer's Ring (WR) region treated at a single institute. Methods: 269 patients with NHL of the WR treated at Tata Memorial Hospital, Mumbai from January 1990 to December 2002 were included. The median age was 45 years and majority of the patients (67%) were males. Systemic symptoms were present in only 16% of patients, primary site was the tonsil in 58%, nasopharynx in 42% and base tongue in 5% of patients. Majority had Diffuse Large B-Cell Lymphoma (85%); 26% patients presented with stage I disease and 66% had stage II disease. Treatment comprised of a combination of chemotherapy (CTh) and radiotherapy (RT) in majority of the patients (71%). Among these patients, 63% received an RT dose of =45Gy. Results: The complete response rate was 68%. After a median follow-up of 57 months, the 5 year DFS &amp; OS for the whole group were 62.2% and 70.1% respectively. Multivariate analysis showed that; age &gt;30 years (HR=4.05, 95%CI=1.53–10.7, p=0.005), WHO performance score =2 (HR=2.36, 95%CI=1.12–4.95, p=0.023), T-cell lymphomas (HR=5.55, 95%CI=2.43–12.7, p&lt;0.001), bulky tumors (HR=2.08, 95%CI=1.02–4.257, p=0.045), and nasopharyngeal primary (HR=3.26, 95%CI=1.51–7.02, p=0.003), had a negative influence on survival. Patients treated with a combination of CTh &amp; RT had a significantly better outcome than those treated with CTh alone (OS: 78.9% vs. 48.1%, p&lt;0.00001). The hazard ratio for death (HR) in the chemotherapy alone group was 3.50 (95% CI=2.17–5.65). The CR (p=0.01), DFS (p&lt;0.0001) and OS (p=0.002) rates were significantly better for patients receiving a RT dose of =45Gy. The HR in the subgroup that received a RT dose of &lt; 45Gy was 5.09 (95% CI=2.39–10.86). Conclusions: Age at diagnosis, WHO performance score, T-cell histological type, size and site of the tumor significantly influence outcome in patients with primary NHL of the Waldeyer's Ring. Combined modality treatment, comprising of CTh &amp; RT (with an RT dose of =45Gy), results in satisfactory outcome in patients with this rare neoplasm. No significant financial relationships to disclose.
Obesity and risk classification for recurrence in clinically localized prostate cancer.
Authors: O. Smaletz, M. C. Lyra, A. T. Paes, G. C. Lemos, E. R. Wroclawski, W. Alfer, V. Ortiz, L. L. da Fonseca Fo., D. Mattos, M. V. Sadi
Journal: Journal of Clinical Oncology (2010)

e15043 Background: Evidence suggests that obesity is biologically associated with the development of prostate cancer (PCa) and may increase the risk of a more aggressive cancer. We investigated if Body Mass Index (BMI) correlates with risk for recurrence in clinically localized disease. Methods: Clinical preoperative data as well as pathological data was retrospectively collected from patients with clinically localized PCa that underwent a radical prostatectomy at our hospital. BMI was calculated and patients were categorized as < 25 kg/m2: normal; 25-29.9 kg/m2: overweight and ≥ 30 kg/m2: obese. Patients were classified according to National Comprehensive Cancer Network (NCCN) risk classification (low risk: T1-T2a and Gleason 2-6 and PSA < 10 ng/ml; intermediate risk: T2b-T2c or Gleason 7 or PSA 10-20 ng/ml; high risk/very high risk: ≥T3a or Gleason 8-10 or PSA > 20 ng/ml). The association between BMI and risk classification was evaluated by Fisher's exact test. Results: One hundred and eighty patients underwent radical prostatectomy between January 2001 and February 2006. Median age was 60 years (range, 53-70), median PSA was5.7 ng/ml (range, 0.9-41.8), median weight was80 kg (range, 57-130) and median BMI is 25.9 (range, 19.3-43.4) with 58 patients (32%) with normal weight, 93 (52%) overweight patients and 29 (16%) obese patients. Overall patient's distribution was low risk: n = 35 (19%), intermediate risk: n = 117 (65%) and high/very high risk: n = 28 (16%). The Table shows patien's distribution according to BMI and risk classification resulting in a significant correlation between these factors (p=0.026). Conclusions: Obese patients have a higher chance of having a more aggressive disease at the time of the diagnosis of localized PCa. NCCN risk classes Normal weight (BMI < 25 kg/m2)(n=58) Overweight (BMI 25-29.9 kg/m2)(n=93) Obese (BMI ≥ 30 kg/m2)(n=29) Low 13 (22%) 15 (16%) 7 (24%) Intermediate 42 (72%) 61 (66%) 14 (48%) High/very high 3 (5%) 17 (18%) 8 (28%) Fisher's exact test: p=0.026 No significant financial relationships to disclose.
Macroeconomic Environment During Infancy as a Possible Risk Factor for Adolescent Behavioral Problems
Authors: Seethalakshmi Ramanathan, Natarajan Balasubramanian, Rajeev Krishnadas
Journal: JAMA Psychiatry (2012)

CONTEXT Economic difficulties at the individual level can lead to a number of behavioral problems, including substance abuse and delinquent behaviors. OBJECTIVE To examine the influence of a nationwide adverse economic environment during infancy, specifically, the high unemployment rates during and after the 1980 and 1981-1982 recessions, on rates of subsequent adolescent substance use and delinquent behaviors. DESIGN We used data from the National Longitudinal Survey of Youth 1997 and estimated logit regressions to examine the effect of changes in unemployment rates during infancy on the incidence of adolescent behavioral problems, controlling for known youth, family, and environmental risk factors. SETTING Adolescents living in the United States in 1997. PARTICIPANTS Nationally representative sample of 8984 adolescents born from January 1, 1980, through December 31, 1984. MAIN OUTCOME MEASURES Probability of engaging in substance use (marijuana, smoking, alcohol, and hard [ie, illegal] drugs) and delinquent behaviors (arrest, handgun use, gang affiliation, petty and major theft, property destruction, and assaultive behavior). RESULTS Exposure to a 1% deviation from mean regional unemployment rates at the age of 1 year was associated with an increase in the odds ratios of engaging in marijuana use (1.09 [95% CI, 1.04-1.14]), smoking (1.07 [1.03-1.11]), alcohol use (1.06 [1.02-1.10]), arrest (1.17 [1.09-1.25]), gang affiliation (1.09 [1.00-1.19]), and petty (1.06 [1.01-1.10]) and major theft (1.11 [1.05-1.18]). No significant associations were noted with use of hard drugs, property destruction, and assaultive behavior. CONCLUSIONS The macroeconomic environment during infancy can have serious long-term effects on substance use and delinquent behavior. These potential long-term effects can play an important role in policy making for adolescent mental health care.
Axillary lymph node metastases from papilloma of the breast
Authors: T. Singh, E. Tso, A. Kumar, P. Ahrens
Journal: Journal of Clinical Oncology (2006)

10764 Background: To report a unique case of papilloma of the breast with metastases to the axillary lymph node. Methods: Case report and review of literature. Results: 80 year old Caucasian male presented with right gynacomastia of 3 months duration. The lesion was resected. Pathology was consistent with intraductal papilloma with hyperplasia and no evidence of malignancy. Subsequently, after 2–3 weeks a mass was noted in the right axilla. This mass was resected and was found to be consistent with papilloma of the axillary lymph node and had the pathological characteristics of the original breast papilloma. Conclusion: Solitary papillomas are generally lesions of the large ducts usually located in the subareolar region of the breast. They are among the commonest cause of spontaneous nipple discharge. After resection of the primary lesion, local recurrence is fairly common. Recurrence is especially common if hyperplasia is associated with the papilloma. There is also an increased incidence of carcinoma in the affected breast. Due to the benign nature of papillomas, they do not metastasize. We did an extensive review of literature and did not find any cases of metastatic lesions from a papilloma of the breast. The underlying reason and pathogenesis for the metastases is not known. No significant financial relationships to disclose.
Lack of an association between human papillomavirus (HPV) infection and colorectal cancer
Authors: P. C. Montenegro, A. Carrato, A. Castillejo, T. Mata Balaguer, V. M. Barbera, E. Ochoa, E. Andrada, C. Guillen, L. Casanova, J. Soto
Journal: Journal of Clinical Oncology (2008)

15111 Background: Molecular studies have demonstrated a direct relationship between human papillomavirus (HPV) infection and invasive cervical cancer, as well as cancer of the anal region. The role of HPV infection in colorectal cancer has not been properly elucidated. Our objetive was to evaluate the presence of HPV infection in the colorectal mucosa and its association with colon and rectal carcinomas. Methods: We analyzed tissue samples from 70 sporadic colorectal cancer patients (30 colon and 40 rectal) and 3 anal canal cancers, diagnosed at our hospital. Normal and tumor tissue samples from each patient were studied. We tested the presence of HPV by PCR amplification of viral L1 gene using primer set MY09/MY11 (MY-PCR) and nested PCR with GP5+/GP6+ primers in the 73 normal and tumor tissue samples. HPV typing was assessed by direct sequencing of the positive cases for HPV detection. Results: HPV was detected in tissue samples from the three anal canal cancer cases. Besides, only one normal colon tissue showed HPV infection. Genotyping analysis showed the HPV type 16 infection in these four positive cases. None of the remaining 70 colorectal cancer cases analyzed (normal and tumor tissues) were positive for HPV. Conclusions: The present study suggests that HPV is not associated with colorectal carcinogenesis. No significant financial relationships to disclose.