tbuckley/cabot-search huggingface dataset:
Multivariate analysis of prognostic variables associated with survival from a phase III study of cisplatin (P) plus etoposide (E) plus chest radiation (XRT) with or without consolidation docetaxel (D) in patients with unresectable stage III non-small cell lung cancer (NSCLC)
Authors: F. O. Ademuyiwa, T. E. Breen, C. Johnson, A. White, C. Yiannoutsos, N. Hanna
Journal: Journal of Clinical Oncology (2007)

7668 Background: Concurrent chemoradiation is standard treatment against stage III NSCLC. HOG LUN 01–24 examines whether consolidation therapy with D improves overall survival. We present an analysis investigating the association of patient characteristics with overall survival from patients on this study. Methods: Eligible patients had untreated stage III NSCLC, FEV1 ≥ 1 liter, PS of 0–1, and weight loss &lt; 5%. Patients received P 50 mg/m 2 days 1, 8, 29, 36 with E 50 mg/m 2 days 1–5, 29–33, and concurrent 5,940 cGy XRT. Patients with non-progressive disease were randomized to D 75 mg/m 2 q3wk X 3 cycles vs observation. A multivariable parametric accelerated failure time model was performed to identify factors that affected survival and to estimate the treatment effect adjusting for these factors. Results: A multivariate analysis was performed on 203 patients who were the subject of a DSMB interim analysis. Median follow up was 25.6 months. Variables analyzed included age (&lt;70 vs ≥ 70), sex, race, body mass index, PS (0 vs 1), FEV-1 (&gt; 2 vs ≤ 2), smoking status, hemoglobin (≥12 vs &lt;12), and stage. A multivariable parametric accelerated failure time model demonstrated the association of age &lt;70 vs =70 years (p=0.0447), FEV1 &gt;2 vs =2 (p=0.0153), and pre-treatment hemoglobin values (p=0.0083) as independent prognostic factors for overall survival. The median survival for hemoglobin &lt;12 was 16.8 vs 21.5 months for hemoglobin ≥12 (p=0.0432). Similarly, the median survival with FEV &gt;2L was 21.6 vs 18.9 months for FEV =2 L. Survival was not significantly influenced by smoking status, sex, race, PS, stage, or BMI. Conclusions: This analysis suggests that age &lt;70, FEV-1 &gt;2L and higher pre-treatment hemoglobin values are associated with improved overall survival in patients with stage III NSCLC. No significant financial relationships to disclose.
A phase I clinical study of biweekly pemetrexed and gemcitabine in patients with advanced solid tumors
Authors: A. Dudek, T. Larson, C. E. Mellskog, L. P. Bloss, C. Obasaju
Journal: Journal of Clinical Oncology (2004)

2141 Background: Pemetrexed (Alimta), a multi-targeted anti-folate, is synergisitic with gemcitabine in preclinical models. The optimal sequence and schedule of both drugs is currently unknown. This is the first study that will examine a biweekly schedule. The purpose of this study was to establish a maximum-tolerated dose (MTD) and recommend a phase 2 dose. Methods: Gemcitabine (G) was infused over 30 minutes, followed immediately by pemetrexed (P) given intravenously over 10 minutes once on day 1 every 14 days. The dose levels examined are shown in Table 1. Table 1. Dose Escalation Levels with DLTs Results: Thus far, 24 patients (13 female, 11 male) with 1 or no prior chemotherapy; median age 61 (range 39 – 80); ECOG PS 0 (11), 1 (13); diagnoses: lung (10), malignant pleural mesothelioma (3), pancreas (3), breast (2), atypical carcinoid tumor (2), head and neck (1), ovarian (1), skin (1), unknown primary (1) have received a current total of 87 cycles (range 1–13/ patient). MTD was established at dose level 5 (G 1500 mg/m2 and P 600 mg/m2) with two patients out of 6 experiencing neutropenic fever (NF). Dose level 4 was then expanded to treat 6 additional patients; no DLTs were seen in any of these 9 patients. Conclusions: G 1500 mg/m2 and P 500mg/m2 was selected as the phase 2 recommended dose. Preliminary response information suggests activity across multiple dose levels with specifics to be discussed at presentation. Plans are to study this schedule in phase 2 trials in many tumor types where G and P are known to be active. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly
Phase I trial of TS-1 plus carboplatin in patients with advanced non-small cell lung cancer: A Central Japan Lung Study Group Trial-CJLSG0402
Authors: H. Saka, C. Kitagawa, M. Ichikawa, Y. Yamada, H. Saito, H. Taniguchi, M. Yamamoto, K. Shimokata
Journal: Journal of Clinical Oncology (2006)

17065 Background: TS-1, a novel oral antimetabolite, is active against advanced non-small cell lung cancer (NSCLC). A response rate of 21.3% was reported in a monotherapy trial. In combination with cisplatin, TS-1 demonstrated a response rate of 47.3% in NSCLC. To develop a clinically relevant combination, we investigated TS-1 plus carboplatin in patients (pts) with advanced NSCLC. This is a report of the phase I section of a phase I/ II trial. In the phase I section, primary endpoints were to determine the maximum tolerated dose (MTD), the recommended dose for the phase II section, and to evaluate the toxic profile. Methods: Pts were enrolled who were chemo-naïve, in stages IIIB and IV, with ages between 20 and 74, PS (ECOG) of 0 or 1, and with adequate bone marrow and major organ functions. Post-surgical relapses and asymptomatic brain metastases were accepted. Pts received a fixed dose of carboplatin (6 mg/mL min) via IV infusion on day 1, once every 3 weeks. TS-1 was given at the initial dose of 60 mg/m 2 (level 1) with dose escalation in 10 mg/m 2 increments from day 1 to day 14, repeated every 3 weeks. Severe toxicities occurring in cycle 1 were considered dose-limiting toxicities (DLTs). Results: Sixteen pts were enrolled in 3 cohorts receiving 60 (n = 3), 70 (n = 7), and 80 (n = 6) mg/m 2 . Median age was 65 years (range, 37 to 74 years) and median performance status was 1. Ten pts had stage IV, and 4 pts had stage IIIB disease. Two pts had post-surgical relapses. Adenocarcinoma (n = 11) was the dominant histology. DLT was observed in 1 pt in level 1, 2 pts in level 2 (TS-1, 70 mg/m 2 ), and 3 pts in level 3 (TS-1, 80 mg/m 2 ). DLTs were grade-4 thrombocytopenia (n = 3), grade-4 neutropenia (n = 1), grade-3 liver dysfunction (n = 1), and grade-3 anorexia (n = 1). Conclusions: The MTD was level 3 (TS-1 80 mg/m 2 , carboplatin 6 mg/mL min). According to the total delivered doses, the recommended dose for phase II study was determined to level 2 (TS-1 70 mg/m 2 , carboplatin 6 mg/mL min). The phase II study is currently underway. [Table: see text] No significant financial relationships to disclose.
Effects of dietary protein intake on muscle protein synthesis and degradation in rats with gentamicin-induced acute renal failure.
Authors: R Baliga, S V Shah
Journal: Journal of the American Society of Nephrology (1991)

In the study presented here, the muscle protein synthesis and degradation in gentamicin-induced acute renal failure were examined in rats fed a low (7%)-, normal (22%)-, and high (35%)-isocaloric protein diet. Male Sprague-Dawley rats were fed equivalent amounts of these diets for 10 days and then received daily subcutaneous injections of either 1 mL of sterile isotonic saline or 100 mg/kg of gentamicin for 7 consecutive days. The rats were sacrificed the following day, and epitrochlearis muscles were obtained for measurement of protein turnover. The serum creatinine in each of the gentamicin-treated groups were significantly higher than that in the saline-treated controls but were no different from each other. Muscle protein synthesis (calculated from the incorporation of radiolabeled (U-14C) phenylalanine) was slightly but not significantly decreased in gentamicin-treated rats as compared with that of the corresponding saline controls in each of the dietary groups. Net protein degradation (the rate of tyrosine release into media) in the 7 and 22% gentamicin-treated groups was similar to that in the corresponding saline controls. In contrast, net protein degradation was significantly greater in the 35% gentamicin group of rats when compared with that in the 7 and 22% gentamicin groups and its own control. In the 7 and 22% saline- and gentamicin-treated protein groups, there was a reduction in net protein degradation in response to insulin. In contrast, the net protein degradation continued to remain significantly elevated in the 35% gentamicin-treated group, despite addition of insulin, when compared with that in the 7 and 22% gentamicin groups and its own control.(ABSTRACT TRUNCATED AT 250 WORDS)
Incidental carcinoma of the prostate: What’s the best procedure to discover residual disease?
Authors: G. Pomara, M. Simone, P. Casale, F. Francesca
Journal: Journal of Clinical Oncology (2008)

16106 Background: Incidental prostate cancer (CaP) presents a highly different risk of progression for T1a and T1b disease (T1a: 10–26% at 7–10 years; T1b: up to 30 % at 2 years), even in more recent series. An incorrect definition of stage can strongly impact on patient’s survival, so we restaged our patients after transurethral resection of the prostate (TURP) by means of a second procedure, consisting of a repeated TURP plus ultrasound-guided biopsies (BxP). The study investigated prospectively these two diagnostic modalities with the aim to discover which one provides the best detection rate. Methods: Between January 1997 through January 2006, 50 T1a CaP were discovered in patients submitted to TURP (1021pts). Median prostate-specific antigen (PSA) before the operation was 5.25 ng/ml (range 0.6 - 17). After three months, prior PSA reevaluation, all patients underwent a second resection in conjunction with an ultrasound-guided transrectal biopsy (six cores). Results: After the first TURP median PSA was 1.35 ng/ml (range 0 - 4.02). Residual disease was demonstrated in 20 patients (40%) [median PSA 1.19 (range 0.4 - 4.02)], then treated surgically or not, depending on age or comorbidities. Among them, in 7 cases (14%) both re- TURP and BxP were positive; in 7 patients (14%) repeated TURP was positive and BxP negative (p n.s.), while in the remaining 6 (12%) repeated TURP was negative and BxP positive (p n.s.). Twelve out of 20 patients (median age 68) with persistent cancer underwent radical surgery and locally advanced disease was revealed in 3 (25%), with one patient having a Gleason score 9. Conclusions: In these series 40% of patients, initially diagnosed in stage T1a, revealed residual tumor after restaging. This high percentage warranted the discomfort and the costs of a second procedure. Either repeated TURP and BxP failed to demonstrate an advantage over each other in terms of “detection rate”. A 10% false negative rate for both prompts us to associate the two modalities instead of choosing between them, in order to discover a potentially lethal residual disease for which, in many cases, a definitive treatment is to be considered. No significant financial relationships to disclose.
Common tumor markers predict extent of disease and success of cytoreductive surgery in patients with appendiceal malignancies
Authors: V. Gushchin, A. Ross, C. Nieroda, B. Kalesan, P. Kostuik, D. Holter, A. Sardi
Journal: Journal of Clinical Oncology (2008)

15527 Background: There are few reliable criteria for selecting patients with peritoneal carcinomatosis of appendiceal origin for cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Tumor markers are known to correlate with prognosis in patients with resectable liver metastases. The hypothesis was that elevated tumor markers are associated with extensive disease and inability to perform complete cytoreduction. Methods: Fifty-four patients underwent CS and HIPEC by a single surgeon for appendiceal malignancies between 1999 and 2007. Tumor markers (CEA, CA 19–9, and CA 125) were measured preoperatively. Preoperative Peritoneal Cancer Index (PCI) score and completeness of cytoreduction (CC) score were recorded. Robust regression analysis assessed the relationship of tumor markers to PCI and CC scores. Overall survival analyses were performed using Kaplan-Meier method. Cox proportional hazard regression models were computed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for disease related mortality and CC score. Results: CEA was elevated in 50.0% of patients, CA 125 in 46.0%, and CA 19–9 in 40.8%. Elevated levels of CEA (>5 ng/mL), CA 125 (>35 U/mL), or CA 19–9 (>37 U/mL) were associated with higher PCI scores (Odds Ratio (OR), 95% CI, p-value: 11.46, 5.90 to 17.01, p<0.0001; 14.92, 9.20 to 20.43, p<0.0001; 10.83, 4.11 to 17.55, p=0.002, respectively). High CC scores (2–3) were associated with elevated CEA and CA 125 (OR, 95%CI, p-value: 6.82, 1.46 to 31.92, p=0.015; 9.89, 1.84 to 53.10, p=0.008 respectively). The overall median survival was 41 months for all patients, 53 months for low CC (0–1) and 30.3 months for high CC (p=0.01). Hazard ratio of disease related death was 7.0 (95% CI, 1.55 to 31.61) among patients with high CC score as compared to those with low CC scores. Conclusions: Elevated tumor markers were associated with high tumor burden and incomplete cytoreduction in patients with peritoneal carcinomatosis of appendiceal origin. Patients with low CC score survived longer. Thus, CEA, CA 125 and CA 19–9 may be useful in selecting patients for CS and HIPEC. No significant financial relationships to disclose.
Clinical outcome of pediatric Hodgkin’s disease in upper Egypt
Authors: E. N. Ebeid, M. Zaghloul, M. Khairy
Journal: Journal of Clinical Oncology (2006)

9035 Background: To assess clinical outcome of chemotherapy and involved field radiotherapy in all stages of pediatric Hodgkin’s Disease in rural areas of Egypt treated at Menya oncology centre which is located 300km south the capital. Methods: Between April 2000 and November 2005, 27 previously untreated patients were investigated, treated and analyzed for remission and survival. Results: There were 21 males and 6 girls with a median age of 11 years, 29.6% were less than 10 years, 70.3% had advanced stage disease (IIB-IV), bulky mediastinal mass in 19 cases spleen involvement in 6 cases, bone marrow aspirate was free in all cases, bone marrow biopsy was not done. patients with stage I and IIA received 2 courses of EOPA (etopsid, vincristine, prednisone and doxorubicin), patients with stage IIb and IIIa received 2 courses of EOPA and 2 courses of ECOP (etopsid, cyclophophamide, vincristine and prednisone), while patients with stage IIIb and IV received 2courses of EOPA and 4 courses of ECOP, All patients received involved field radiotherapy according to stage. Complete remission was achieved in 96.2%. Progressive disease in 1 (3.7%) which required change line of therapy. Out of the 27 patients 3 (11.1%) have relapsed (17, 22 and 25 months) post completion of chemotherapy and were treated with another line of chemotherapy. The 2 years DFS was 90.9% with 95% of CI (73%-100%). Treatment was given outpatient, with no supportive therapy or toxic deaths and no secondary malignancy from etopsid Conclusions: This regimen provides high rate of durable remission in rural areas of Egypt with limited resources (drugs availability and supportive measures). No significant financial relationships to disclose.
Effect of neoadjuvant abiraterone acetate (AA) plus leuprolide acetate (LHRHa) on PSA, pathological complete response (pCR), and near pCR in localized high-risk prostate cancer (LHRPC): Results of a randomized phase II study.
Authors: Mary-Ellen Taplin, Robert B. Montgomery, Christopher Logothetis, Glenn J. Bubley, Jerome P. Richie, Bruce L. Dalkin, Martin G. Sanda, Massimo F. Loda, Lawrence D. True, Patricia Troncoso, Elizabeth M. Genega, Steven P. Balk, Peter Nelson, Wanling Xie, Christopher M. Haqq, Namphuong Tran, Cameron S. Liu, Thian San Kheoh, Arturo Molina, Philip Kantoff
Journal: Journal of Clinical Oncology (2012)

4521 Background: LHRPC is infrequently cured with prostatectomy (RP). To date neoadjuvant androgen deprivation therapy (ADT) has not improved outcomes and residual intra-prostatic androgens remain. AA lowers serum testosterone (T) and DHT to &lt; 1 ng/dL and has improved survival in advanced PC. Methods: We conducted a neoadjuvant, phase II trial of AA/LHRHa in LHRPC. The primary aim was to evaluate intra-prostatic T/DHT with LHRHa vs LHRHa/AA. We report secondary endpoints of PSA, pCR and near pCR ([≤ 5mm residual tumor]) and safety. Eligibility: ≥ 3 positive biopsies and either Gleason ≥ 7 (4+3), T3, PSA ≥ 20 ng/mL or PSA velocity &gt; 2 ng/mL/year. For the first 12 wks men were randomized to LHRHa or LHRHa/AA/prednisone (P) 5mg qd. After 12 wks, a prostate biopsy was done to measure T/DHT. Men received 12 more wks of LHRHa/AA/P followed by RP. Results: 58 men enrolled: 28 to initial LHRHa and 30 to initial AA/LHRHa. 2 withdrew prior to RP (1/group). Median age was 58 (50-75). pCR/near pCR was 14/56 (25%). Grade 3 AEs included elevated AST/ALT 5/58 (9%) and hypokalemia 3/58 (5%). No grade 4 mineralocorticoid-related AEs were observed. Conclusions: Neoadjuvant ADT with AA was well tolerated in LHRPC. PSA (&lt;0.2) declines were high and achieved earlier on AA/LHRHa compared to LHRHa. The pCR/near pCR rates were higher for 24 wks AA (34%) than 12 wks AA (15%). No new safety signals were seen with AA used with P 5 mg. These results support further evaluation of aggressive ADT as neoadjuvant/adjuvant therapy for LHRPC. [Table: see text]
Irofulven (IROF) combined with oxaliplatin (OXA) in advanced hepatocellular carcinoma (HCC) patients (pts): Phase I study (preliminary results)
Authors: F. Goldwasser, N. Houédé, F. Bertheault-Cvitkovic, J. Misset, E. Raymond, B. Benettaib, C. Kahatt, J. R. MacDonald, G. Weems
Journal: Journal of Clinical Oncology (2006)

14082 Background: IROF, a semisynthetic derivative of the natural product illudin S, is a novel DNA binding agent that has demonstrated antitumor activity in pts with a variety of chemoresistant tumors. Currently available systemic chemotherapy offers limited benefit to HCC pts. Evidence of IROF activity in HCC was seen with IROF 11 mg/m 2 daily x4 every 28 days (Stuart et al, ASCO 2003), and every other week dosing schedules (Falcon et al, ASCO 2004). Preclinically, IROF exhibits additive and synergistic antitumor activity in combination with OXA. Methods: Dose escalation was performed in pts with HCC and other advanced malignancies in this Phase I study. Dose levels (DL) were OXA (mg/m 2 )/IROF (mg/kg): DLI: 40/0.3; DLII: 40/0.4; DLIII: 50/0.4; DLIV: 60/0.4; DLV: 70/0.4; DLVI: 80/0.4. OXA (2-hour infusion) was followed by IROF (30-min infusion) on Days 1 and 15 every 28 days. Results: Of the 41 pts treated, 8 had HCC, 2 treated at DLI and 6 at DLVI. Median age of these 8 pts was 48 years; PS (ECOG) 0/1: 1/7; median AFP 1253 ug/L (range 16–39760); 3 pts had a history of hepatitis (B/C : 2/1) and 2 of cirrhosis; 3 had prior chemotherapy and 3 chemoembolization; all but one had metastatic disease. Safety: A median of 3 cycles was given (range 1+ to 5+). One pt experienced grade (G) 3 vomiting, 5 pts G1–2 asthenia and nausea, 4 G3 thrombocytopenia and 3 G3 neutropenia. Efficacy: Activity was seen in 6 of the 8 HCC pts, (DLI: 1; DLVI: 5); 1 confirmed PR with AFP decrease from 1250 to 1.9 (99.8%; DLVI) and PFS of 3.5+ months; 1 PR, non-confirmed (42% AFP decrease, 20741 to 11974; DLVI) with PFS of 3.6 months, and 4 SD (DLI: 1; DLVI: 3) were observed with a median duration of 3.6 months (3.2–6.0 +); 3 SD pts (3.8, 3.9 and 3.2+ month duration) had 12%, 52% and 36% AFP decrease respectively. Based on activity in the whole cohort and in the absence of an MTD, DLVI (80/0.4) was selected as the recommended dose. Conclusions: Combined IROF/OXA shows substantial activity and is well tolerated in advanced HCC pts. Additional HCC patients will be included at the RD to evaluate the efficacy of IROF/OXA in this indication. [Table: see text]
Knowledge of cancer risk factors.
Authors: K. M. Gil, S. Yeropoli, B. Fish, L. Schnegg, J. L. Savitski
Journal: Journal of Clinical Oncology (2010)

1570 Background: Knowledge is a precondition for reducing modifiable risk factors and undergoing appropriate screening. This study assessed women's level of knowledge concerning risk factors for gynecologic cancers. Methods: Women attending an Ob/Gyn resident clinic or private Ob/Gyn practice were asked if getting older, being overweight, not exercising, smoking, family history, and HPV virus increased the risk of breast, endometrial, cervical and ovarian cancer. These choices included 9 risk factors identified by the American Cancer Society which are likely to affect a large proportion of women (e.g., being overweight and endometrial cancer, www.cancer.org). A composite score equal to the number of these risk factors selected was calculated. Self reported demographic information was collected. Regression analysis was used to assess the effect of age, level of education, clinic/private practice, smoking status, exercising regularly for more than 6 months and race on composite score. Results: Virtually all women completed the questionnaire (94.6%; clinic, n = 377; private practice, n = 301). Mean age was 36.4 ± 0.5 (SEM), 29% smoked, 27% were African American, 67% were Caucasian, 27% reported exercising regularly, and 62% had at least some college. The majority responded that family history was a risk factor for breast, endometrial, cervical and ovarian cancer (93%, 77%, 77%, 84%, respectively). Over half (53%) selected family history, but not being overweight, as risk factors for endometrial cancer. Women attending the clinic were less likely to check that smoking and the HPV virus were risk factors for cervical cancer (smoking: 34% vs. 44%, p = 0.008; HPV virus: 60% vs. 74%, p < 0.001) although their rate of smoking was higher (43% vs. 12%, p < 0.001). The composite score was less than 3 for 51% of women; 6% scored the maximum of 9. Having at least some college, exercising and being Caucasian were associated with higher composite scores while age, smoking status and clinic/private practice did not significantly affect scores. Conclusions: While family history may receive more attention and be more familiar to women, being overweight, smoking and growing older will affect more women. Women, especially those with less education, are not understanding their relative risk of developing cancers. No significant financial relationships to disclose.