NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors (breast/colorectal/lung/pancreatic)

Mistletoe Extract and Gemcitabine - open access



Conclusion
The combination of mistletoe and gemcitabine was well tolerated and treatment compliance was high. The MTD was gemcitabine 1380 mg/m2 weekly on day one and eight of a 3-week cycle combined with mistletoe 250 mg daily. Gemcitabine pharmacokinetics were not affected by mistletoe. The lack of febrile neutropenia even at higher gemcitabine doses is noteworthy. The formation of ML antibodies is common. A consistent effect of the study regimen on the serum levels of selected cytokines could not be demonstrated. Clinical response of the combination appeared to be similar to single agent gemcitabine reported previously. 

(focus on MSH6) Functional Analysis in Mouse Embryonic Stem Cells Reveals Wild-Type Activity for Three Msh6 Variants Found in Suspected Lynch Syndrome Patients

open access

Introduction

Lynch Syndrome (LS), also called hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominant disorder that is characterized by early onset cancer of the colorectum and endometrium. It furthermore confers an increased risk for cancers of the ovary, small intestine, stomach, ureter, renal pelvis, brain and sebaceous glands [1]. Tumors often show a high rate of microsatellite instability (MSI). The majority of LS cases is caused by inherited mutations in the DNA mismatch repair (MMR) genes MLH1 and MSH2 (70-80% of all LS-associated colorectal cancer (CRC) cases). Mutations in the MMR genes MSH6 and PMS2 account for the remaining 20-30% of LS-associated tumors [2,3]. MMR gene mutation carriers generally have an up to 10-fold increased lifetime risk of developing CRC (70-80%) and endometrial cancer (40-60%) compared to the general population [4].
In contrast to families carrying MLH1 and MSH2 mutations, families carrying mutations in MSH6 often do not fulfill the criteria for LS diagnosis. Tumors in MSH6 mutation carriers frequently show no or low MSI and the observed instability is generally restricted to mononucleotide markers [5–7]. When compared to MLH1 and MSH2 mutation carriers, the age of onset is generally later for MSH6 mutations carriers (approximately 10 years) and they have a lower risk for developing CRC [2,3]. There are reports of increased frequency of endometrial cancer in MSH6 mutation carriers versus MSH2 mutation carriers [8]; however, two large studies found no difference [2] or even a decreased [3] endometrial cancer incidence in patients carrying a mutation in MSH6.....



 

Identification of Ovarian (serous) Cancer Metastatic miRNAs (2013)

open access

Abstract

Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.....

Table S1.

Summary of Patient Characteristics.

doi:10.1371/journal.pone.0058226.s009

(XLSX)

 

Prognostic factors for chemotherapy induced nausea and vomiting

abstract

"Purpose: to review the topic of prognostic factors for chemotherapy-induced nausea and vomiting. Multiple patient factors such as age, gender and alcohol intake have been found that affect the likelihood of emesis with a given chemotherapy. Pharmacogenomics has also been explored as a cause for variation in emetic response. In theory these risk factors could be used to optimize antiemetic therapy for individual patients but guidelines for prophylactic antiemetics are based solely upon the type of chemotherapy administered. Attempts to identify subgroups of patients for whom guidelines recommendations are suboptimal have thus far been unsuccessful except for those with a poor experience in a previous cycle of the same chemotherapy. At present, there is no basis for deviating from evidence-based guidelines when prescribing antiemetics prior to the first cycle of chemotherapy." 

Hope in Newly Diagnosed Cancer Patients

Hope 

Context

Hope is important to cancer patients as it helps them deal with their diagnosis. Little is known about hope in newly diagnosed cancer patients.

Objectives

Based on the Transcending Possibilities conceptual model of hope, the purpose of this study was to examine the relationship of hope with pain, energy, and psychological and demographic characteristics in newly diagnosed adult oncology outpatients.

Methods

Data from 310 New Patient Assessment Forms from cancer outpatients' health records were collected. Health records from the first six months of 2009 were reviewed and data were collected on hope, energy, pain, depression, anxiety, feeling overwhelmed, and demographic variables. A generalized linear modeling approach was used to study the relationship of hope scores with these variables. Hypothesized variables and variables that were significant at the P = 0.01 level from the univariate analysis were entered into the multivariate model, with hope scores as the dependent variable.

Results

Hope scores were significantly negatively related to age (P = 0.02). More specifically, oncology patients who were 65 years of age or older had significantly less hope than those under the age of 65 years (P = 0.01). Gender (P = 0.009) also was a significant factor, with men having higher hope scores than women. No other variables were significant.

Conclusion

Older adults comprise the majority of persons in Canada with cancer. The lower hope scores found in this age group compared with their younger counterparts underscore the importance of further research. This study provides a foundation for future research in this important area for oncology patients.

 

Breakthrough Cancer Pain: An Observational Study of 1000 European Oncology Patients

abstract

Context

Breakthrough pain is common in patients with cancer and is a significant cause of morbidity in this group of patients.

Objectives

The aim of this study was to characterize breakthrough pain in a diverse population of cancer patients.

Methods

The study involved 1000 cancer patients from 13 European countries. Patients were screened for breakthrough pain using a recommended diagnostic algorithm and then questioned about the characteristics and management of their pain.

Results

Of the 1000 patients, 44% reported incident pain, 41.5% spontaneous pain, and 14.5% a combination. The median number of episodes was three a day. The median time to peak intensity was 10 minutes, with the median for patients with incident pain being five minutes (P < 0.001). The median duration of untreated episodes was 60 minutes, with the median for patients with incident pain being 45 minutes (P = 0.001). Eight hundred six patients stated that pain stopped them doing something, 66 that it sometimes stopped them doing something, and only 107 that it did not interfere with their activities. Patients with incident pain reported more interference with walking ability and normal work, whereas patients with spontaneous pain reported more interference with mood and sleep. As well, 65.5% of patients could identify an intervention that improved their pain (29.5%, pharmacological; 23%, nonpharmacological; 12%, combination). Regarding medications, 980 patients were receiving an opioid to treat their pain, although only 191 patients were receiving a transmucosal fentanyl product licensed for the treatment of breakthrough pain.

Conclusion

Breakthrough cancer pain is an extremely heterogeneous condition.

 

Role of hyperthermic intraoperative peritoneal chemotherapy in the management of peritoneal metastases

abstract

The peritoneal cavity must be oncologically considered as an organ in its own right and peritoneal metastases (PM) must be treated with the same curative intent (and the same results) as liver metastases. The package combining complete cytoreductive surgery (CCRS) (treating the visible disease) plus hyperthermic intraoperative peritoneal chemotherapy (HIPEC) (treating the remaining non-visible disease) achieves cure in many patients. Twenty years of publication allow us to assemble sufficient background information and data to point out the good and poor indications for CCRS+HIPEC. HIPEC is the standard of care for the treatment of peritoneal pseudomyxomas and peritoneal mesotheliomas and also, recently for the treatment of colorectal PM with limited peritoneal extension. HIPEC is in the evaluation phase for gastric PM and ovarian PM after initially disappointing results, but it is highly probable that it will be useful in particular settings. PM from neuroendocrine tumours are in the same situation. HIPEC is not currently indicated for the treatment of PM from sarcomas, from GIST, and for small round-cell desmoplastic tumours, given the poor results obtained. HIPEC can be useful, on a case-by-case basis, to treat rare tumours complicated by isolated peritoneal diffusion (e.g. Frantz's tumours). HIPEC can be used in the prophylactic setting to prevent PM in patients with a high risk of developing PM, and the first results of the 'second-look' approach are promising. Finally, CCRS+HIPEC appear to be indispensable tools in the oncologist's armentarium. 

Hematuria Patients Rarely Referred for Cancer Screening

Hematuria Patients