tbuckley/cabot-search huggingface dataset:
Oral chemotherapy: A focus on interventions and access.
Authors: Robert Mancini, David Wilson, Jessie Modlin, Dan Sayam Zuckerman, Colleen Powell, Delisa Rapp, Jill Collins, Thea Hutchinson
Journal: Journal of Clinical Oncology (2012)

44 Background: Oral chemotherapies are becoming more predominant with 40% of the currently available oral agents being approved in the last 7 years. Patient self-administration and the costs of these medications raise concerns about monitoring and access. As a result, nonfulfillment rates in the literature have been reported to range from 10-24% with rates directly correlated with cost of the medication. Methods: Patients who utilized the pharmacist-managed oral chemotherapy program were included for evaluation. Patients were excluded if they utilized external mail order pharmacies. Patient charts were audited for documented pharmacist-initiated interventions such as drug-interactions, lab monitoring, and dose adjustments. Patient nonfulfillment rates were evaluated by evaluating percentage of patients referred to number of prescriptions filled. Patients were classified as either filled, mail order, financial assistance or never started. Financial assistance patients were divided into free drug or co-pay assistance. Total amount of free drug obtained was assessed by multiplying the average number of cycles obtained by patients by the average wholesale price (AWP). Results: A total of 702 patients were served by the Oral Chemotherapy program between August 2009 and October 2011. In those patients, 82 drug-drug interactions and 24 patients required dose adjustments up front, mostly due to renal dysfunction. Compared to the 10-24% nonfulfillment rates in the literature, this program was able to keep rates less than 1% for patients who were unable to obtain medication for financial reasons. In this time period, underinsured patients were able to obtain &gt;$1 million in free drug and &gt;$200,000 in co-pay assistance funds thanks to our financial advocates. Conclusions: Collaboration within one health system between oncologists, pharmacists, nurses and social workers/financial advocates was able to ensure better quality of care by helping address medication issues upfront with minimal delays in access. In addition, this program was able to ensure that most patients were able to obtain their medication within a reasonable time period at a reasonable cost, reducing non-fulfillment rates compared to what has previously been reported in the literature.
Japan-SWOG common arm analysis of paclitaxel/carboplatin in advanced stage non-small cell lung cancer (NSCLC): A model for prospective comparison of cooperative group trials
Authors: D. R. Gandara, Y. Ohe, K. Kubota, Y. Nishiwaki, Y. Ariyoshi, N. Saijo, S. Williamson, P. N. Lara, J. Crowley, M. Fukuoka
Journal: Journal of Clinical Oncology (2004)

7007 Background: Whether results of clinical trials performed outside the United States (US) can be fully extrapolated to US populations remains in question due to potential differences in trial designs, study-specific criteria, patient demographics, and population-related pharmacogenomics. Methods: We prospectively designed & conducted separate phase III trials in advanced NSCLC linked by a “common arm” with identical eligibility, staging, response & toxicity criteria, to: 1) determine similarities & differences in patient demographics & outcomes in cooperative group trials in Japan (Four Arm Cooperative Study or FACS) & the US (SWOG 0003), 2) provide the basis for global standardization in clinical trials in NSCLC, and 3) facilitate regulatory changes needed for joint Japan-US studies sponsored by the US National Cancer Institute (NCI). We performed a planned comparative analysis of the paclitaxel/carboplatin arms from FACS & S0003, identical except for paclitaxel dose of 200mg/m2 in FACS, 225mg/m2 in S0003, based on the MTD from separate phase I studies in Japan and the US. Carboplatin: AUC 6 in both. Results: Conclusions: 1) This common arm analysis shows great similarities in patient demographics between the FACS and S0003. 2) Variable toxicities may be due to differences in cumulative paclitaxel dose (neuropathy) and/or population-related pharmacogenomics (increased neutropenia & febrile neutropenia in FACS despite lower paclitaxel dose). 3) Survival is increased in FACS. 4) Future joint Japan-US clinical trials should consider possible pharmacogenomic differences in drug disposition. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
CD125-Expressing Myeloma: A Subgroup of Multiple Myeloma (MM) with Immature Phenotype, Endoplasmic Reticulum Stress Response and Low Sensitivity to Bortezomib
Authors: Yawara Kawano, Yoshitaka Kikukawa, Miki Nakamura, Yutaka Okuno, Hiromichi Yuki, Shiho Fujiwara, Hiroaki Mitsuya, Hiroyuki Hata
Journal: Blood (2010)
A phase I trial of chemoradiation therapy with concurrent full dose gemcitabine for unresectable locally advanced pancreatic adenocarcinoma
Authors: T. Ioka, S. Tanaka, A. Nakaizumi, K. Nishiyama
Journal: Journal of Clinical Oncology (2005)

4209 Purpose: The primary objective of this study is to assess the toxicity of radiotherapy with concurrent full dose Gemcitabine (GEM) for unresectable locally advanced pancreatic cancer. Patients and Method: Between 04/01 and 06/02, twelve patients were entered to this trial. GEM was planned to be administered at a dose of 1000 mg/m2 weekly for 3 weeks during RT. The starting RT dose was 30 Gy in 2.0 Gy fractions. Escalation was achieved by increasing the duration in 5 fractions increments, keeping the fraction size in 2.0 Gy. PTV was planned to be GTV+ 1–2cm with inclusion of regional nodes. DLT was defined as grade 4 thrombocytopenia, grade 4 neutropenia, or grade 3 nonhematologic toxicity. Every twelve patients were evaluated for response with RECIST criteria by an extramural radiologist, Dr. Natsuo OHYA (Kyoto Univ. Dept. of Radiation Oncology). Results: Average tumor size was 4.1cm (2.3–7.0cm) and PTV volume was 195 cm3 (92–375 cm3). Treatment was well tolerated; twelve patients completed all protocol therapy. No patient experienced DLT. We experienced six patients (50%) of grade 3 neutropenia, two patients (17%) of grade 2 thrombocytopenia and six patients (50%) of grade 2 nonhematologic toxicity. Six patients (50%) had evidence of a local anticancer effect. Five of these six patients (41.5%) had a complete or partial response to therapy. The median survival for the entire group was 16.5 months. The 1-year and 2-year survival rate for patients was 58.3% and 25.0%. Conclusion: The Chemoradiation therapy with cocurrent full dose GEM can be delivered safely for unresectable locally advanced pancreatic cancer. No significant financial relationships to disclose.
Phase II trial of combined chemotherapy with irinotecan, S-1, and bevacizumab (IRIS/Bev) in patients with metastatic colorectal cancer: Update analysis—Hokkaido Gastrointestinal Cancer Study Group (HGCSG) trial.
Authors: Satoshi Yuki, Yoshito Komatsu, Takuto Miyagishima, Takashi Kato, Kazuteru Hatanaka, Michio Nakamura, Mineo Kudo, Nobuaki Akakura, Miki Tateyama, Yuh Sakata
Journal: Journal of Clinical Oncology (2012)

3593 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853–860) previously demonstrated the non-inferiority of Irinotecan plus S-1(IRIS) to FOLFIRI for metastatic colorectal cancer(mCRC), with progression-free survival (PFS) as the primary endpoint. We previously reported that IRIS plus bevacizumab(IRIS/bev) is very effective as first-line treatment (Komatsu Y et al. ESMO 2010). We now report the updated results of this study. Methods: Eligible patients had to have mCRC with a confirmed diagnosis of adenocarcinoma, an age of &gt;20 years, ECOG performance status (PS) of 0-1, and no history of prior chemotherapy. S-1 40-60 mg twice daily p.o. was given on days 1-14 and irinotecan 100 mg/m 2 and bevacizumab 5 mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS). Results: The target number of 53 patients was enrolled as of March 2009. The results are reported for 52 patients with evaluable lesions. The clinical characteristics of the patients were as follows. The median age was 63.5 years (range, 48 to 82). The male:female ratio was 3:2. The performance status on the Eastern Cooperative Oncology Group scale was 0. In January 2012, on safety analysis, the incidence of grade 3 or 4 neutropenia was 27%. The incidences of other grade 3 or 4 adverse reactions were as follows: diarrhea, 17%; anorexia, 4%; stomatitis, 2%; hypertension, 21%; and gastrointestinal perforation, 0%. The overall response rate was 63.5%. Three patients had complete response. Thirty patients had partial response, 16 had stable disease, none had progressive disease, and 3 were not evaluable. Median progression-free survival was 17.0 months and median survival time was 39.6 months. Conclusions: IRIS/Bev is a remarkably active and generally well-tolerated first-line treatment for patients with mCRC. Randomized control trial comparing this regimen with oxaliplatin containing regimen(XELOX or mFOLFOX6 plus bevacizumab) is being planned.
Chemotherapy for advanced non-small cell lung cancer with interstitial lung disease.
Authors: E. Ichihara, N. Takigawa, A. Hisamoto, K. Hotta, M. Tabata, K. Kiura, M. Tanimoto
Journal: Journal of Clinical Oncology (2010)

e18122 Background: The treatment of lung cancer with interstitial lung disease (ILD) is challenging because the treatment, including surgery, chemotherapy, and radiotherapy, can itself induce interstitial pneumonia (IP) or exacerbate preexisting ILD. Usually, clinicians hesitate to treat lung cancer with ILD. Information on the treatment of non-small cell lung cancer (NSCLC) with comorbid ILD is extremely limited; additionally, it is not known whether chemotherapy is beneficial in advanced NSCLC patients with ILD, because most clinical trials exclude patients with ILD. Methods: We retrospectively reviewed the medical records of chemotherapy-treated advanced NSCLC patients with comorbid ILD, including idiopathic interstitial pneumonia (IIP), collagen vascular disease interstitial pneumonia (CVD-IP), pneumoconiosis, and pulmonary sarcoidosis at our institution between April 1998 and March 2007 and evaluated the overall survival and acute exacerbation rates. Results: Forty cases were treated with chemotherapy and the median overall survival was 17.5 months (95% confidence interval 15.2–19.9), which is comparable with that for advanced NSCLC without ILD. Multivariate analysis revealed that poor performance status (PS) and an elevated serum KL-6 level predicted a poor overall survival. Five cases (13%) developed an acute exacerbation of preexisting ILD during treatment and two of these patients died of the exacerbation (5%). Acute exacerbation occurred not only in IIP but also in CVD-IP and pneumoconiosis. Conclusions: Chemotherapy might have survival benefit in some NSCLC patients, even with comorbid ILD. However, to treat this safely, it is necessary to avoid those patients at a high risk of acute exacerbation (poor PS, elevated serum KL-6). To determine the efficacy of chemotherapy in NSCLC patients with a good PS, normal KL-6, and comorbid ILD, further prospective study is needed. No significant financial relationships to disclose.
Erythropoiesis Stimulating Agent (ESA) Use for Anemic Cancer and Chronic Kidney Disease (CKD) Patients in 2008: Advocacy for Conservative Use
Authors: Charles L. Bennett, Benjamin Kim, Athena T Samaras, Allen R Nissenson, A. Oliver Sartor, D. Mark Courtney, Robert I. Liem, Dennis P West, Simone N Boyle, Robin L Wagner, Carolyn E Goldstein, Steven M Trifilio, David M Spiegel, Stephen Y Lai
Journal: Blood (2008)
Incidence, timing, and severity of anemia with dose-dense breast cancer adjuvant chemotherapy
Authors: N. P. Uppal, J. Griggs
Journal: Journal of Clinical Oncology (2005)

8264 Background: The purpose of this study was to characterize the incidence, timing, and severity of anemia in breast cancer patients receiving dose dense adjuvant chemotherapy. Methods: We performed a retrospective cohort study of 36 consecutive patients treated with dose dense combination chemotherapy. Information on patient and treatment characteristics, serial hematocrit (Hct) levels, chemotherapy details, and treatment of anemia were abstracted from the medical records. Descriptive statistics were generated and T-tests and Fisher’s exact tests performed as appropriate. Results: Of the 36 patients, 34 had a decline in Hct during the course of chemotherapy. The mean Hct decline was 7 percentage points (SD 4%). A decline in the Hct of 6 percentage points or more was seen in 24 patients (.67, 95% confidence interval .49, .81), and a decrease in Hct of 10 percentage points or more was seen in 11 patients (.31, 95% confidence interval .16, .48). In bivariate analyses, age was the only factor associated with a decline in Hct of 6 + percentage points. In patients 65 years and over, the mean Hct decline was 10 percentage points compared with 6 in those under 65 (p = .016). The decline in Hct was not associated with the type of surgery, breast reconstruction, or the number of courses of chemotherapy. The maximum drop in Hct occurred most often by the beginning of treatment cycle 4 (n = 14, 39%) or 5 (n = 7, 19%). Three patients (8%) were transfused. Fourteen patients were treated with erythropoietin; 12 of the 14 were started on this drug after the lowest Hct was reached. Of the 24 patients with a Hct drop of 6+ percentage points, 9 were treated with erythropoietin compared with 5 of the 12 with a drop of less than 6 (p = 1.0). Conclusions: Declines in Hct, sometimes severe, are common in patients treated with dose-dense adjuvant chemotherapy for breast cancer, particularly in those who are older. The time to maximal decline in Hct is fairly predictable, which may allow for more rational and guideline-driven use of erythropoietin. No significant financial relationships to disclose.
Cutaneous malignancies identified in an inpatient dermatology consultation service
Authors: S. Tsai, J.F. Scott, J.J. Keller, M.R. Gerstenblith
Journal: British Journal of Dermatology (2017)

The role of inpatient Dermatology consultation and biopsy in evaluating suspicious cutaneous lesions is unknown.1-3 Previous studies analyzed the diagnostic accuracy and utility of consultations for common rashes and infectious diseases, without considering suspicious lesions.4-6 We sought to describe the frequency, clinicopathologic characteristics, and outcomes of suspicious lesions biopsied on an inpatient Dermatology consult service

This article is protected by copyright. All rights reserved.
Population pharmacokinetics of NKTR-102, a topoisomerase I inhibitor-polymer conjugate, in patients with advanced solid tumors.
Authors: M. A. Eldon, U. Hoch
Journal: Journal of Clinical Oncology (2011)

2598 Background: NKTR-102 demonstrates significant anti-tumor activity with a tolerable toxicity profile in pts with platinum-resistant/refractory ovarian or metastatic breast cancers. NKTR-102 is a novel topoisomerase I inhibitor that uses Nektar’s proprietary polymer conjugation to improve the PK of its active metabolite SN38 resulting in significantly reduced Cmax and sustained exposure throughout the dosing interval. Methods: NKTR-102 was administered as a 90-min IV inf. to 94 pts: 76 pts at 58-245 mg/m2 wx3q4w, q14d or q21d, and 18 pts at 100 or 125 mg/m2 q21d receiving concurrent cetuximab. Serial plasma samples were collected for the duration of treatment and assayed by LC-MS/MS for NKTR-102, irinotecan, SN38, SN38-Glu, and APC. Results: NKTR-102 and metabolites followed biphasic disposition kinetics with first-order appearance rates consistent with their metabolic progression (Tmax 1.5-24 hr) and first-order terminal t1/2 between 21-61 days. PK of NKTR-102 and all metabolites were independent of dose and schedule. BSA was a significant covariate for CL. SN38 CL was lower (30%) in females and lower (30%) in pts who were homozygous for UGT1A1*28, but these reductions were not considered clinically important. Patient age, hepatic and renal functions were not correlated with SN38 CL. Coadministration of cetuximab had no effects on NKTR-102 PK and vice versa. PK in pts with ovarian and breast cancer were similar to those with non-ovarian or -breast tumors. The RP2D (145 mg/m2) results in approx. the same plasma SN38 AUC as 350 mg/m2 of irinotecan, but exposure is continuous rather than intermittent and Cmax is 10-fold less. Conclusions: NKTR-102 results in sustained systemic exposure to SN38 between infrequent doses while preventing exposure to excessively high concentrations; these enhancements appear responsible for improved efficacy and tolerability profiles. The PK of NKTR-102 and metabolites are predictable and do not require complex dosing adjustments and support ongoing Phase 2 clinical development as single-agent in metastatic breast, platinum-resistant ovarian, and metastatic colorectal cancers.
Phase II study of capecitabine (X) as single agent in elderly patients (p) with metastatic breast cancer (MBC): Final results
Authors: P. Zamora, M. Álvarez de Mon, L. Calvo, C. Jara, J. A. Virizuela, A. Yubero, J. Chacón, J. Mira, M. González Barón
Journal: Journal of Clinical Oncology (2006)

10709 Background: X is a selectively tumour-activated fluoropyrimidine active in solid tumours. Twice-daily oral administration of X enables chronic dosing that mimics a continuous infusion of 5-FU. In p with pretreated advanced BC, X is effective as monotherapy and also in combination with other agents. Some studies have shown that safety data of X in general population also apply to elderly p. The objective of this study is to evaluate the toxicity profile and response rate of X in elderly p with MBC. Methods: P histologically confirmed of breast adenocarcinoma, metastatic disease, age ≥70 years, ECOG PS &lt;2, measurable disease and adequate bone marrow, renal and hepatic functions were included. Prior X, CNS metastases or radiotherapy within 4 weeks of treatment start was not allowed. P received X monotherapy 1250 mg/m 2 b.i.d. (X 950 mg/m 2 in p with creatinine clearance 30–50 ml/min), days 1–14 every 3 weeks for a maximum of 9 cycles. P can be previously treated with chemotherapy, hormonotherapy or radiotherapy for the metastatic disease. Clinical response was evaluated every 3 cycles (RECIST). Results: Twenty three p were enrolled with histology confirmed adenocarcinoma, median age was 77 years old (68–88) and ECOG PS 0/1 in 33%/67% of p. Surgery was performed in all p. Adjuvant chemotherapy and hormonotherapy was administered in 65% and 74% of p, respectively. Prior chemotherapy for MBC was administered in 13.0% of p. Median number of metastatic lesions was 3 (90% with ≥2 sites), in bone (57%), lung (43%), liver (43%) and lymph nodes (38%) mainly. A total of 117 cycles (median 4, range 1–9) were administered. Median RDI was 86% and 100% for X 1250 mg/m 2 and X 950 mg/m 2 , respectively. All p were evaluable for toxicity. Grade III/IV toxicity per patient were hand-foot syndrome (13%), asthenia (13%), mucositis (9%), diarrhoea (9%), neutropenia (4%), thrombocytopenia (4%), nausea (4%) and vomiting (4%). Efficacy analysis: over 16 evaluable p, 2 achieved PR, 7 SD and 7 PD, resulting in an ORR of 13% (95% CI: 0–29). Median TTP was 7.5 months (95% CI: 4.5–10.5), median OS was 13.3 months (95% CI: 9.6–16.9) and one year survival 55.5% (95% CI: 33.7–77.2). Conclusions: Twice daily oral X seems to be an effective and well tolerated treatment in pretreated elderly MBC p. No significant financial relationships to disclose.
Addition of panitumumab to irinotecan: Results of PICCOLO, a randomized controlled trial in advanced colorectal cancer (aCRC).
Authors: M. T. Seymour, S. R. Brown, S. Richman, G. W. Middleton, T. Maughan, C. Olivier, S. J. Gwyther, J. Wadsley, I. Chau, T. Hickish, L. K. Dawson, S. Falk, A. O'Callaghan, K. Benstead, N. Wadd, A. Oliver, P. Chambers, H. Marshall, V. Napp, P. Quirke
Journal: Journal of Clinical Oncology (2011)

3523 Background: Phase III trials show inconsistent effects when anti-EGFR drugs are added to cytotoxic therapy in aCRC. Benefits, when present, are confined to patients (pts) determined retrospectively to have KRAS wild-type (wt) tumours. PICCOLO is a multicentre randomized controlled trial, amended in June 2008 to include prospective KRAS testing, to evaluate the addition of panitumumab (Pan) to single-agent irinotecan (Ir) as second- or subsequent-line therapy for KRAS-wt aCRC. Methods: Eligible pts had: measurable aCRC progressing during/after ≥1 prior regimen with fluoropyrimidines ± other drugs; no prior Ir; WHO PS 0-2. Until June '08, pts were allocated 1:1:1 to Ir, IrPan or Ir/ciclosporin, with retrospective KRAS analysis. Thereafter, KRAS was tested prospectively (by pyrosequencing of c.12-13 and 61) and pts with KRAS-wt were allocated 1:1 to Ir (Ir 350 mg/m2 [300 mg/m2 if ≥70 yrs or PS2], q3w) or IrPan (same Ir plus Pan 9 mg/kg, q3w). Primary analysis is ITT overall survival (OS) in KRAS-wt pts not pretreated with anti-EGFR therapy (80% power, HR 0.70, α=0.05, 2-sided). Secondary endpoints include % progression-free at 12 wks, PFS, RR, toxicity and QL. Planned molecular subgroups include BRAF, NRAS, KRAS c.146 and PIK3CA. Results: 460 KRAS-wt pts were recruited to the primary analysis (324 after June '08, KRAS-tested prospectively); median age 63 yrs; 94% PS0-1; 95% had received prior oxaliplatin. With 312 events and median follow-up of survivors 10.2 mo, OS was not improved: median IrPan = 10.4 mo, Ir = 10.5 mo, HR 0.91 (95%CI [0.73, 1.14], p=0.44), but trended towards improved survival after 12 mo. Planned subgroup analysis shows worse survival, and disbenefit with Pan in BRAF-mut pts (n=63, HR=1.87, [95%CI 1.07, 3.27]); conversely, KRAS/BRAF-wt pts show a stronger but still non-significant trend towards benefit (n=348, HR=0.86 [0.66, 1.11]). Conclusions: PICCOLO did not meet its primary endpoint of improved OS with panitumumab in KRAS-wt aCRC, but a trend was seen towards survival benefit after 12 months, especially in KRAS/BRAF-wt pts. Conversely, pts with BRAF-mut tumours had significant disbenefit with Pan. Full results, including PFS and planned molecular subgroups, will be presented.