tbuckley/cabot-search huggingface dataset:
The effect of cytotoxic chemotherapy on the risk of high-grade acneiform rash with cetuximab in cancer patients: A meta-analysis.
Authors: Y. Balagula, S. Wu, X. Su, S. W. Dusza, M. E. Lacouture
Journal: Journal of Clinical Oncology (2010)

9072 Background: Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor monoclonal antibody, is approved for head and neck cancer in combination with radiotherapy and for colorectal cancer as single agent or combined with irinotecan. Its combined use with chemotherapy in these and other types of cancer has been undergoing active investigation. Papulopustular rash (acneiform rash) is the most common adverse effect. This analysis was done to investigate the risk of high-grade (grade ≥3) acneiform rash in a setting of cetuximab in combination with cytotoxic chemotherapy. Methods: Relevant studies were identified from PubMed (1998 to 2009) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2009. Eligible studies were limited to prospective randomized controlled Phase II-III clinical trials in which cancer patients were treated with cetuximab 400 mg/m2 initially, followed by weekly 250 mg/m2, in combination with chemotherapy. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 5,272 patients with a variety of solid cancers from 13 randomized controlled clinical trials were included for analysis. The overall incidence of high-grade acneiform rash associated with cetuximab in combination with chemotherapy was 10.3% (95% CI: 7.6-13.9%). There was a significantly increased risk of high grade acneiform rash with cetuximab in combination with chemotherapy in comparison with controls (chemotherapy alone) (RR=37.8, 95% CI: 16.8-85.4%, p value<0.001). When compared to our previous analysis of high-grade acneiform rash with cetuximab monotherapy (6.5%), patients receiving combination treatment are at increased risk of developing severe acneiform rash (RR=1.6, 95% CI: 1.2-2.0%, p-value<0.0001). Conclusions: Cancer patients treated with cetuximab in combination with cytotoxic chemotherapy are at substantial risk for developing high-grade acneiform rash. The addition of chemotherapy may significantly increase the risk of rash associated with cetuximab. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems Bristol-Myers Squibb Bristol-Myers Squibb, ImClone Systems, Novartis, Onyx Pharmaceuticals, Pfizer, Wyeth Hana Biosciences
Residual neurotoxicity in patients with ovarian cancer in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: The Multicenter Italian Trials in Ovarian cancer (MITO-4) retrospective study
Authors: M. Di Maio, R. V. Iaffaioli, S. de Placido, R. Biamonte, G. Scambia, G. Di Vagno, A. Febbraro, G. Colucci, C. Pisano, S. Pignata
Journal: Journal of Clinical Oncology (2005)

5015 Background: carboplatin/paclitaxel (CP) is the chemotherapy (CT) of choice for advanced ovarian cancer. Although a significant proportion of patients (pts) have some neurotoxicity during treatment, the long-term outcome of CT-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of pts in clinical remission after first-line CP for advanced ovarian cancer. Patients and Methods: 120 consecutive pts have been enclosed in this study. All pts received C (AUC 5) plus P (175 mg/m2) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. 49 pts (41%), assigned to the experimental arm of the MITO-1 study, had received 4 courses of topotecan (1.5 mg/m2 for 5 days every 3 weeks) after CP, as consolidation therapy. Data have been collected between May and September 2004. Residual sensory and motor neurotoxicity have been coded according to the NCI CTC v2.0. Results: 55 pts (46%) did not experience any grade of neurological toxicity during CT: none of them had signs of neuropathy during follow up. The other 65 pts (54%) had CT-induced neurotoxicity during treatment and follow-up data are available for 60 of them. 46/60 pts (77%) had no residual neuropathy at the moment of interview: in detail, recovery from neurotoxicity had occurred in the first 2 months after the end of CT in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 (15%). The remaining 14/60 pts (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months): 12 pts had G1 and 2 pts G2 peripheral sensory neuropathy; 3 pts had also G1 motor neuropathy. Overall, at 6 months, 23 out of 120 pts (19%) had some residual neurotoxicity. Conclusions: our data indicate that a significant proportion of patients with advanced ovarian cancer treated with first-line CT with carboplatin/paclitaxel suffer long-term residual neuropathy. This issue should be carefully taken into account before considering a re-treatment with the same agents in sensitive recurrent disease. No significant financial relationships to disclose.
Proportion of subjects with an ethically acceptable reason for enrolling in a phase I trial
Authors: R. D. Pentz, F. Khuri, J. Kauh, T. Owonikoko, M. M. White, R. D. Harvey
Journal: Journal of Clinical Oncology (2009)

2512 Background: Concern persists that phase I subjects, who frequently enter trials for personal benefit, are deluded. They may suffer from therapeutic misconception (TM) - conflating research and clinical care, or from therapeutic misestimation (TMis) - misestimating benefits or risks. Methods: To estimate the proportion of phase I subjects who have an ethically acceptable reason for participation, we both interviewed and surveyed subjects to obtain qualitative and quantitative data. Ethically acceptable reasons included 1) Altruism (sole motive for entering trial was to help others or advance science); 2) Self-regarding motives but no TM (correctly identifying that the trial mostly intends to help research and gain knowledge, the study decides the treatments and the subjects get different doses of drug); 3) Self-regarding motives, TM but no TMis (chance of benefit &lt; 20% and chance of risk &gt; 0%); or 4) Self-regarding motives, TM, overestimation of benefits but broad view of benefit (with collateral benefits like getting careful disease monitoring or access to an academic center listed) and chance of risk &gt; 0%. This generous interpretation of ethically acceptable reasons hinges on the view that subjects at least must recognize there is some risk, that chance of disease benefit is not high and that collateral benefits count. Results: The 86 subjects were mostly white, male, with incomes more than $60,000. 49% were college educated with a mean age of 60. 53.5% had an ethical reason for participation, with 10.5% altruistic, 16.3% no TM, 8.1% TM but no TMis, and 18.5% overestimating benefit but including collateral benefits. In both univariate and multivariate analyses age younger than 60 yo and having at least a college education were the only characteristics significantly correlated with having an ethically acceptable reason for participation. Those who reported strong religious beliefs (p = 0.01) were significantly more likely not to have an ethically acceptable reason. Conclusions: With almost half of participants lacking an ethically acceptable reason for participation, interventions are necessary to bolster understanding. Older participants lacking a college education are particularly at risk and could be the target for an intervention trial. No significant financial relationships to disclose.
Palliative prognostic tools for the terminally ill patients with gastric cancer.
Authors: Beodeul Kang, Hye Jin Choi, Sun Young Rha
Journal: Journal of Clinical Oncology (2014)

120 Background: Terminally ill patients with gastric cancer have specific gastrointestional symptoms and signs related with cancer progression. To estimate accurate survival expectancy of gastric cancer patients is important for timely decision making of their end of life issues. Methods: We reviewed the 276 patients with terminally ill gastric cancer who were treated at Yonsei Cancer Center between January 2007 and December 2011 and eventually were died. Retrospectively, we conducted the data of clinical signs, symptoms, and laboratory results at the time of cessation of the active treatment. Then, we established the palliative survival estimation model by stratification of risk group. Results: Median palliative survival time from the decision to stop further treatment to death was 42days. In the multivariate Cox regression analysis, 5 parameters were identified as prognostically significant factors: anorexia, dyspnea, hypoalbuminemia, elevated blood urea nitrogen, and elevated serum alkaline phosphatase. We scored each variables as 1-3 for symptom(1:asymptomatic, 2:symptomatic, 3:symptomatic requiring intervention) and 1-2 for lab results(1:normal, 2:abnormal) and summed up each scores. Using the total score, patients were divided into 3 risk groups: low-risk(5-7points), intermediate-risk(8-11points), and poor-risk patients(12point). As a result, median palliative survival for low-risk group(n=110) was 87.0±7.4days, intermediate-risk group(n=158) and poor-risk group(n=8) were 31.0±2.1days and 6.0±2.1days, respectively (p&lt;0.0001). Conclusions: Using multivariate analysis and summation of each prognostic factor score, 3 risk groups were determined. After validation by prospective multicenter trial, this palliative survival time estimation tool will be helpful to inform the accurate survival for terminally ill gastric cancer patients.
Quality of life assessment in clinical oncology: Implications for prognosis in advanced colorectal cancer
Authors: R. D. Levin, D. Gupta, S. Hoffman, J. Granick, R. Neelam, P. G. Vashi, M. Daehler, T. Wodek, K. Quinn, C. G. Lis
Journal: Journal of Clinical Oncology (2004)

3699 Background: Quality of Life (QoL) assessment is important to evaluate the impact of disease and treatment in patients with advanced cancer. Recently, it has been hypothesized that QoL may also have a prognostic role in cancer, however, there is little evidence in the literature to support this view. To further investigate this issue, we evaluated the prognostic significance of baseline QoL in patients with advanced colorectal cancer. Methods: We examined a case series of 31 histologically confirmed stages III and IV colorectal cancer patients treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center between March 2001 and January 2003. Two fundamentally different QoL tools were utilized in this study. The EORTC QLQ-C30 (EORTC) emphasizes the patient's capacity to fulfill the activities of daily living, while the Ferrans and Powers Quality of Life Index (QLI) highlights the level of patient satisfaction with life. Study patients were dichotomized into two groups based on the median scores for all QoL domains for both the EORTC and QLI. Kaplan Meier method was used to calculate survival. Log-Rank test was used to study the equality of survival distributions. Results: Patients with high global health EORTC scores had a median survival of 21.2 months while those with low scores 13.6 months (p = 0.08). Additional EORTC QoL domains significantly associated with survival included role function (median survival of 13.6 months for low vs. 23.9 for high scores) and social function (median survival of 13.6 months for low vs. 23.9 for high scores), p = 0.09 and 0.06 respectively. For QLI, only health and physical functioning was significantly associated with survival (p = 0.09), with the median survival for low scores being 13.6 months and 21.3 months for high scores. Conclusions: This study suggests that baseline QoL assessment provides useful prognostic information in patients with advanced colorectal cancer. Similar studies in other cancer types with larger sample sizes are needed to further validate the prognostic significance of QoL in advanced cancer. No significant financial relationships to disclose.
Neoadjuvant paclitaxel poliglumex (PPX), cisplatin, and radiation (RT) for esophageal cancer.
Authors: T. Ng, J. Fontaine, M. Suntharalingam, T. Dipetrillo, M. N. Horiba, N. B. Oldenburg, K. Perez, W. Chen, F. Habr, H. Safran
Journal: Journal of Clinical Oncology (2010)

4085 Background: Paclitaxel poliglumex (PPX) is a drug conjugate that links paclitaxel to poly-L-glutamic acid thereby increasing its radiation enhancement factor to 4.0-8.0 compared to 1.5-2.0 for paclitaxel. In previous phase I studies, The Brown University Oncology Group evaluated PPX with concurrent radiation and PPX/cisplatin/RT. A phase II study was subsequently performed to evaluate the pathologic response rate of neoadjuvant PPX, cisplatin and radiation for patients with esophageal cancer. Methods: Eligible patients had pathologically confirmed adenocarcinoma or squamous cell carcinoma of the esophagus or GE junction with no evidence of distant metastasis. Patients received weekly PPX 50 mg/m2 and cisplatin 25 mg/m2 for 6 weeks with concurrent 50.4 Gy of radiation. Six to eight weeks after completion of chemoradiotherapy, patients underwent surgical resection. Results: The study completed accrual of 40 patients, 37 with adenocarcinoma and 3 with squamous cell cancer. The median age is 62 years. One of 40 (2%) patients developed a grade 4 hypersensivity reaction. Treatment related grade 3 non-hematologic toxicities included esophagitis (7%), nausea (7%), fatigue (5%). Only one patient required a feeding tube and 1 patient used TPN. There were no grade 4 hematologic toxicities and 2 patients (5%) had grade 3 neutropenia. Three patients with clinical endoscopic complete responses (two with squamous cell cancer) refused surgery. Twelve of 37 patients (32%) had pathologic complete responses. The 12 patients with pathologic CR all had adenocarcinoma. Conclusions: PPX, cisplatin and concurrent radiation is a well tolerated, easily administered regimen for esophageal cancer with a low incidence of significant esophagitis and a high pathologic complete response rate consistent with the preclinical data of PPX and radiation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Cell Therapeutics
Response and long-term outcomes after neoadjuvant chemotherapy: Pooled dataset of patients stratified by molecular subtyping by MammaPrint and BluePrint.
Authors: Stefan Gluck, Femke De Snoo, Justine Peeters, George Somlo, Lisette Stork-Sloots, Laura J. van 't Veer
Journal: Journal of Clinical Oncology (2012)

10 Background: Classification of breast cancers into molecular subtypes may be important for the proper selection of therapy for patients with early breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome (Sorlie, PNAS, 2001; Esserman, BCRT, 2011). Herein, we analyze using MammaPrint together with an 80-gene molecular subtyping profile (BluePrint) the response to neo-adjuvant chemotherapy and long term outcomes. Methods: This study was carried out on data from 144 patients from the I-SPY I trial; 232 patients from biomarker discovery program at MD Anderson (133 and 99 respectively; Hess, 2006, JCO; Iwamoto, 2011, BCRT); and 68 patients from City of Hope (Somlo, ASCO, 2010). All patients were treated in the neo-adjuvant setting with standard chemotherapy. MammaPrint and BluePrint were determined on 44K Agilent arrays run at Agendia or available through the I-SPY 1 data portal, or from Affymetrix U133A arrays. MammaPrint and BluePrint resulted in 4 distinct molecular groups: Luminal A (MammaPrint Low-risk/Luminal-type), Luminal B (MammaPrint High-risk/Luminal-type), Basal-type and HER2-type. Results: The overall pCR of this patient cohort was 22% but differed substantially among the subgroups. pCR was observed in 5% of the Luminal-A samples and 10% of Luminal-B, in 39% of the HER2-type samples and in 33% of the Basal-type samples. Patients with Basal-type tumors had a 5-year DFS of 71%; HER2-type had a 5-year DFS of 67% (n=71); 69% in HER2-type subgroup not treated with HER2-targeted therapy (n=45); Luminal-B type had a 5-year DFS of 77% and Luminal-A type showed 5-year DFS of 95%. Conclusions: We observed marked differences in response and DFS to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. These findings confirm differences in chemotherapy response among molecular subgroups and indicate that the BluePrint and MP profile used for this analysis helps to further establish a clinical correlation between molecular subtyping and treatment outcomes.
Phase II study of tasquinimod in chemotherapy-naive patients with metastatic castrate-resistant prostate cancer (CRPC): Safety and efficacy analysis including subgroups.
Authors: A. J. Armstrong, M. Haggman, W. M. Stadler, J. R. Gingrich, V. J. Assikis, O. Nordle, G. Forsberg, M. A. Carducci, R. Pili
Journal: Journal of Clinical Oncology (2011)

126 Background: Tasquinimod (TASQ) is an oral quinoline-3-carboxamide derivative that binds to S100A9 and displays anti-angiogenic and anti-tumor activity in prostate cancer (PC) models. In a randomized blinded phase II study, 206 (136 TASQ, 70 placebo [P]) men with metastatic castrate resistant (CRPC) were assigned to TASQ/P once-daily at an initial dose level of 0.25 mg/day escalating to 1.0 mg/day over 4 weeks. The primary endpoint to demonstrate an improvement in PCWG2 criteria-defined progression at 6 months was met and presented at ASCO 2010. This abstract provides an update on safety and efficacy including CRPC subgroups. Methods: Subgroups of patients based on baseline criteria were investigated for safety using NCI CTC v 3.0 criteria, PK and efficacy. Results: 201 (134 TASQ, 67 P) pts with a median age of 72.6 years received treatment and were evaluable for efficacy and safety. The updated analysis based on 5 additional PFS events confirmed an improved PFS of 7.6 vs. 3.3 months for pts on TASQ vs. P. Most progression events in both arms were radiological, but more pts progressed on bone scan in the P group. Radiographic PFS was 8.8 vs 4.4 months. Significant PFS improvements were observed in the PCWG2 risk groups with bone metastatic and visceral disease. TASQ treatment led to a transient increase in inflammatory lab markers such as CRP and fibrinogen, as well as asymptomatic increases in amylase/lipase. CRP increase was associated with adverse events (AEs) such as muscle and joint pain, while increased amylase was associated with a lower risk for gastrointestinal AEs. TASQ treatment was associated with anaemia, but did not affect CV risk factors such as hypertension or QTc prolongation, and the rate of composite cardiac events was acceptably low. Clearance of TASQ is decreased with age (1.4 % per year) and patients over 80 often required dose reduction due to increased exposure and toxicities. Conclusions: TASQ improved PFS in men with metastatic CRPC. Side effects are manageable and seem to correlate with laboratory markers. Individualized dosing based on tolerability is recommended and a phase III placebo-controlled study is being initiated. [Table: see text]
Clinical outcome of local recurrence cases after endoscopic mucosal resection (EMR) for Japanese Classification stage 0 esophageal cancer.
Authors: T. Yoshii, S. Ohkawa
Journal: Journal of Clinical Oncology (2010)

4135 Background: Endoscopic mucosal resection (EMR) is minimally invasive. When esophageal cancer (EC) is limited to mucosa (Japanese Classification stage 0), EMR is the standard curative therapy with good outcome. Although local recurrence (rec.) is reportedly from 2.8% to 7.8%, their clinical outcome has not been reported fully, so far. Herein, we investigated the detailed outcome of local rec. cases after EMR for stage 0 EC. Methods: We conducted retrospective research on patients(pts.) who underwent EMR for stage 0 EC and could be followed-up for at least one year. Local rec. was determined by finding a new lesion around the EMR scar without residual lugoul-voiding area (LVL) at the end of EMR. Patients who had received prior radiotherapy or chemotherapy were excluded. Follow-up endoscopy was performed every six months, basically. Results: Between January 2002 and November 2008, 137 pts. with 151 lesions underwent EMR for stage 0 EC. Ten of them (10 lesions) had local rec. (6.6%). Two were female and the median age was 67.5 years (range: 62-79). The median follow-up and local rec. free period were 61.7 months (range: 42.8- 93.8) and 9.5 months (range: 2-36), respectively. The median diameter of primary lesions was 27 mm (range: 20-50). Most recurrent lesions were superficial type, after piecemeal resection. Five cases had multiple LVL. Although one patient needed chemoradiation for recurrence, the others could be re-treated endoscopically (re-EMR: 3, EMR + argon plasma coagulation (APC): 2, APC: 4). Five of the latter pts. experienced second local recurrence, and were treated by radical surgery (1); radiotherapy (1); and APC (3). Only one case experienced third local rec, and was treated by radiotherapy. The median time to second local rec. was 15.0 months (range: 2-24.6). Finally, 6 of the rec. cases could be managed endoscopically, and the overall percentage was 97.3% (147 of 151). Two cases dropped out endoscopic treatment because of too large lesion. None experienced systemic metastasis or cause-specific death. Conclusions: Most local rec.cases could avoid invasive treatment, repeating endoscopic treatment. The overall outcome of EMR for stage 0 EC was good. Hence, long-term routine endoscopy is important after the first EMR. No significant financial relationships to disclose.
Reduced symptom burden after visiting an outpatient supportive oncology clinic.
Authors: Kathryn C. Wrammert, Gwendolynn Harrell, Michael O'Neill, Anjali Grandhige, Zachary O. Binney, Tammie E. Quest
Journal: Journal of Clinical Oncology (2014)

204 Background: Outpatient palliative care in supportive oncology clinics (SOC) is growing and has shown promise in controlling symptoms. We sought toinvestigate the impact on symptom burden of a SOC in a National Cancer Institute-designated Comprehensive Cancer Center. Methods: New and returning SOC patients referred from our health system’s oncologists from November 2011 through May 2014 completed the Condensed Memorial Symptom Assessment Scale plus a sexual dysfunction structured assessment. Visits include a structured symptom assessment and personalized treatment plan from the clinic’s part-time physician and/or nurse practitioner. Patients rated from 0-4 how bothersome 15 cancer symptoms were. Descriptive statistics were calculated. We used the Wilcoxon signed rank test to compare symptom scores at patients’ first and second visits. Results: 135 patients had multiple SOC visits. Mean age was 54.7 (SD 12.5) years. 55.3% were female. The most common cancers were breast, lung, and head and neck (18.1% each). Median time between visits was 29 days (mean: 52.8, range: 2-446). The most bothersome symptoms at baseline were pain (mean 3.1, SD 1.3), lack of energy (2.4, SD 1.3), and difficulty sleeping (2.1, SD 1.6). Least bothersome were dyspnea (0.8, SD 1.1), sexual problems (0.9, SD 1.4), and nausea (1.0, SD 1.3). Energy, pain, drowsiness, constipation, sleep, worrying, sadness, and nervousness were significantly improved at follow-up with reductions between 0.2 (drowsiness) and 0.5 (pain) points (all p&lt;0.05). Weight loss trended toward improved (p=0.053). Conclusions: 8 of 15 symptoms significantly improved after the first visit to a small-scale SOC. These reductions may underestimate the SOC’s effect if disease was progressing or overestimate differences if disease was shrinking, but such data were unavailable. Larger multi-site trials with well-defined interventions and control groups are needed.