Tyrosine kinase inhibitors (TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors (GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence- and experience-based consensus to guide the management of TKI-associated side events in clinical practice.

EOX (epirubicin, oxaliplatin, Xeloda; capecitabine) and FOLFOX4 (5-fluorouracil (5-FU), leucovorin, oxaliplatin) are the common chemotherapy regimens used in the treatment of advanced gastric cancer (aGC) in Hong Kong. This study aimed to compare the costs of these therapies for aGC patients from both the healthcare and societal perspectives. It should be noted that, while FOLFOX4 is routinely administered in an outpatient setting in North America and Europe, inpatient setting is adopted in Hong Kong instead, incurring hospitalization cost as a result.

Fifty-eight patients were identified from the electronic records in two public tertiary hospitals, with 45 and 13 receiving EOX and FOLFOX4 regimens, respectively. Healthcare cost was direct medical costs including drugs, clinic follow-up, hospitalization, diagnostic laboratories, and radiographs. Societal cost refers to indirect costs such as patient time and travel costs. Cost items were further classified as "expected" or "unexpected". All cost data was expressed in US dollars.

Patients in the EOX and FOLFOX4 arm received an average of 5.3 and 7.8 cycles of treatment, respectively. The capecitabine-based regimen group had a higher expected medication cost per cycle when compared to the 5-FU-based treatment group (US$290.3 vs US$66.9, p < .001), but lower expected hospitalization costs (US$76.9 vs US$1,269.2, p < .001). The total healthcare cost and total societal cost per patient was reduced by 67.2% (US$5,691.9 vs US$17,357.4, p < .001) and 25.3% (US$3,090.5 vs US$4,135.1, p = .001), respectively, in the capecitabine-based regimen group. Sensitivity analyses based on full cycle regimen costs and net capecitabine or 5-FU/leucovorin costs still showed EOX to be less costly than FOLFOX4.

The capecitabine-based regimen, EOX, was found to generate significant cost saving from both the healthcare and societal perspectives in regions in which FOLFOX4 is given in an inpatient setting.

Short term side-effects of chemotherapy include fatigue, nausea, vomiting, mucositis and myelosuppression or neutropenia. These occur during the course of treatment and generally resolve within months of completion of chemotherapy. A variety of Chinese medicinal herbs have been used for managing these side effects.

To assess the effectiveness and safety of Chinese medicinal herbs in alleviating chemotherapy-induced short term side effects in breast cancer patients.

We searched The Cochrane Breast Cancer Specialised Register (15/02/2007), The Cochrane Central Register of Controlled Trials (CENTRAL); (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to December 2006); EMBASE (1990 to December 2006); and Chinese Biomedical Literature (2006, Issue 4). A number of journals were hand searched.

Randomised controlled trials comparing chemotherapy with or without Chinese herbs in women with breast cancer.

Two authors independently extracted the data, which were analysed using RevMan 4.2. For dichotomous data, we estimated the relative risk. For continuous data, we calculated the weighted mean difference.

We identified seven randomised controlled trials involving 542 breast cancer patients undergoing or having recently undergone chemotherapy. All studies were conducted and published in China. We did not pool the results because few studies were identified and no more than two used the same intervention. All were of low quality and used CMH plus chemotherapy compared with chemotherapy alone.CMH combined with chemotherapy showed no statistically significant difference for the outcomes of phlebitis and alopecia. Only one study showed an improvement in nausea and vomiting, and in fatigue. Three indicated an improvement in white blood cells in the group receiving CMH. Two showed an increase in percentage changes in T-lymphocyte subsets CD4 and CD8. One study showed a statistically significant difference for CMH in percentage changes in T-lymphocyte subsets CD3, CD4 and CD8. Two herbal compounds may have improved quality of life. One study reported that CMH may have some effect on reducing toxicity in liver and kidney, but differences were not statistically significant.

This review provides limited evidence about the effectiveness and safety of Chinese medicinal herbs in alleviating chemotherapy induced short term side effects. Chinese medicinal herbs, when used together with chemotherapy, may offer some benefit to breast cancer patients in terms of bone marrow improvement and quality of life, but the evidence is too limited to make any confident conclusions. Well designed clinical trials are required before any conclusions can be drawn about the effectiveness and safety of CHM in the management of breast cancer patients.

Chemotherapy-induced nausea and vomiting (CINV) is among the most feared side effects of cancer treatment. Poorly controlled CINV may lead to additional office visits or emergency room admissions, thus increasing the overall costs of cancer care. The objective of the project was to estimate the societal costs of uncontrolled CINV among working-age cancer patients.

The 1997-2002 Health and Productivity Management database, a proprietary database linking medical claims to work loss information, was used. The study population consisted of employees or their spouses who were cancer patients treated with highly or moderately emetogenic chemotherapy regimens. Costs of uncontrolled CINV were estimated by comparing the direct medical costs and indirect costs between those with and without uncontrolled CINV; all costs were normalized as monthly costs and updated to 2006 US dollars. The Wilcoxon Mann-Whitney test was used to compare the costs differences in univariate analyses, followed by multivariate analyses.

In all, 2,018 patients were identified; 1,771 (88%) received 5-HT(3) receptor antagonists, and uncontrolled CINV was found in 563 (28%). The estimated monthly medical costs associated with uncontrolled CINV were approximately 1,300 dollars higher for cancer patients at working ages. Subgroup analysis concluded that indirect costs per patient per month were 433 dollars higher for those in the uncontrolled CINV group.

Despite a prevalent use of the 5-HT(3) receptor antagonists, uncontrolled CINV remained a common and costly problem among cancer patients treated with highly or moderately emetogenic chemotherapy.

Chemotherapy-induced nausea and vomiting (CINV) are major adverse effects of cancer chemotherapy. We compared the impact of acute (during the first 24 hours postchemotherapy) and delayed (days 2 through 5 postchemotherapy) CINV on patients' quality of life (QoL) after highly or moderately emetogenic chemotherapy (HEC and MEC, respectively).

This prospective, multicenter, multinational study was conducted in 14 medical practices on cancer patients undergoing either HEC or MEC treatment. Patients recorded episodes of nausea and vomiting in a diary. Patients completed the Functional Living Index-Emesis (FLIE) questionnaire at baseline and on day 6.

A total of 298 patients were assessable (67 HEC patients, 231 MEC patients). Emesis was reported by 36.4% of patients (13.2% acute, 32.5% delayed) and nausea by 59.7% (36.2% acute, 54.3% delayed). HEC patients reported significantly lower mean FLIE total score than MEC patients (95.5 v 107.8 respectively; P = .0049). Among all patients, the nausea score was significantly lower than the vomiting score (50.0 and 55.3, respectively; P = .0097). Of the 173 patients who experienced neither vomiting nor nausea during the first 24 hours postchemotherapy, 22.9% reported an impact of CINV on daily life caused by delayed CINV.

CINV continues to adversely affect patients' QoL despite antiemetic therapy even after treatment with only moderately emetogenic chemotherapy regimens, and even in the subgroup of patients who do not experience nausea and vomiting during the first 24 hours. On the basis of the FLIE results in this study, nausea had a stronger negative impact on patients' daily lives than vomiting.

Needle anxiety not only impacts on a patient's quality of life but can delay or prevent future medical care. Our survey of women with breast cancer indicated that 78/208 women (37.5%) reported feeling anxious about injections. Patients who reported needle anxiety were significantly younger (t(206)=3.72; P<0.01), with a lower body mass index (BMI) (t(182)=2.16; P<0.05), experience of chemotherapy (chi(2)(1)=8.29; P<0.01), a lower internal health locus of control (t(187)=2.28; P<0.05) and higher levels of state (t(197)=-3.58; P<0.01) and trait anxiety (t(197)=-2.30; P<0.05). Patients repeatedly highlighted the experience of chemotherapy as having caused their needle anxiety. Patient discourse suggests that chemotherapy related needle anxiety is a result of physical (e.g. finding a suitable vein) and environmental (e.g. the chemotherapy room) factors. Patients with cancer require psychosocial support during all stages of care, this should include the application of techniques to prevent or ameliorate the development of anxiety caused by certain aspects of cancer treatments, such as the development of chemotherapy-related needle anxiety.

Chemotherapy-induced nausea and vomiting (CINV) are among the most feared side effects of cancer treatment. With increasingly more complex chemotherapy treatments, CINV plays an important role in determining patients' quality of life, as well as when to halt potentially lifesaving therapy. Although significant progress has been made in the treatment of CINV, patients undergoing chemotherapy continue to report that this side effect is persistent and distressing. In 2003, two new agents were added to the armamentarium of antiemetic therapy. The U.S. Food and Drug Administration approved palonosetron, a longer-acting serotonin antagonist, and aprepitant, a neurokinin-1 antagonist and the first in a new class of antiemetics, for the treatment of CINV. Although the indications for both agents are similar, they have distinct differences. Decisions regarding placement of these agents into existing antiemetic protocols can be based on national guidelines, review of the literature, and clinical experience. This article will review current antiemetic therapy with an emphasis on the new additions to the treatment of CINV. Aprepitant and palonosetron represent significant changes in the treatment of CINV. Oncology nurses need to know current approaches to maximize effective antiemetic therapy.

Insulin and dexamethasone are potent inhibitors of apoptosis induced by transforming growth factor-beta1 (TGF-beta) in hepatoma cells. Using FTO-2B rat hepatoma cells, we determined whether the anti-apoptotic effects of these agents result from interference within or upstream of the TGF-beta-induced caspase cascade. Activation of different initiator and effector caspases, Bax and Bcl-xL expression, mitochondrial cytochrome c release and activation of PKB/Akt were analyzed by use of synthetic caspase substrates and Western blotting, respectively. TGF-beta-induced apoptosis was characterized by release of cytochrome c from mitochondria and activation of caspases-3, -7, -8 and -9. These effects were observable as early as 8-12 h after start of treatment and increased with time of observation. Inhibition of TGF-beta-induced apoptosis by insulin and dexamethasone was paralleled by a strong reduction of caspase-3-like activity. Caspase-8 activation was almost completely suppressed by these agents, and caspase-9 activity was decreased to levels within or slightly above unstimulated control cells. In addition, cytochrome c release from mitochondria was efficiently repressed, which was associated with upregulation of Bcl-xL by dexamethasone and activation of PKB/Akt by insulin. Thus, both anti-apoptotic compounds exert their inhibitory effects through modulation of anti-apoptotic signalling pathways involved in regulation of cytochrome c release and activation of the caspase machinery.

The emetic action of the prostanoid TP receptor agonist, 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619; 300 microg/kg, i.p.), was investigated in Suncus murinus. The emetic response was reduced by 76% following bilateral abdominal vagotomy (P<0.001) and by reserpine (5 mg/kg, i.p., 24 h pretreatment; P<0.05) but U46619 administered i.c.v. (30-300 ng) was not emetic, suggesting a peripheral mechanism involving monoamines. However, fenfluramine (5 mg/kg, repeated treatment) and para-chlorophenylalanine (100-400 mg/kg) and ondansetron (0.3-3 mg/kg) were inactive (P>0.05) to reduce U46619-induced emesis precluding a role of 5-HT and 5-HT(3) receptors in the mechanism. Similarly, phentolamine (0.3-3 mg/kg), propranolol (3 mg/kg), and their combination, and metoclopramide (0.3-3 mg/kg), domperidone (0.3-3 mg/kg), droperidol (0.3-3 mg/kg), scopolamine (0.3-3 mg/kg) and promethazine (0.3-3 mg/kg) were inactive (P>0.05) to reduce the retching and vomiting response. However, the tachykinin NK(1) receptor antagonist, (+)-2S,3S(-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2-phenylpiperidine) (CP-122,721; 1-10 mg/kg) antagonized emesis (P<0.01). In conclusion, U46619-induced emesis appears to be mediated via a predominant peripheral mechanism sensitive to reserpine and is not likely to involve adrenoceptors, dopamine, 5-HT(3), muscarinic or histamine (H(1)) receptors. The action of CP-122,721 to reduce U46619-induced emesis extends the spectrum of anti-emetic action tachykinin NK(1) receptor antagonists to mechanisms involving TP receptors.

Aprepitant (Emend) is the first commercially available drug from a new class of agents, the neurokinin NK(1) receptor antagonists. Oral aprepitant, in combination with other agents, is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy in adults. In three randomised, double-blind, placebo-controlled trials comparing aprepitant (125 mg day 1, 80mg once daily on days 2 and 3 or 2-5) plus standard therapy (intravenous ondansetron and oral dexamethasone) with standard therapy plus placebo, overall complete responses (primary endpoint, defined as no emesis and no rescue therapy) were seen in significantly more patients in the aprepitant arms (63-73% versus 43-52%, p < 0.01 for all comparisons). Complete responses and complete protection during the acute and delayed phase, and overall complete protection were also observed in significantly more patients in the aprepitant arms. The difference between treatment groups was more marked in the overall and delayed phases than in the acute phase. The antiemetic efficacy of aprepitant plus standard therapy in the prevention of CINV was maintained for up to six cycles of chemotherapy. Where assessed, more patients in the aprepitant plus standard therapy arms than the standard therapy plus placebo arms reported no impact of CINV on daily life, as assessed by the Functional Living Index-Emesis. Aprepitant is generally well tolerated. The most common adverse events in randomised trials were asthenia or fatigue. Other adverse events experienced by aprepitant recipients include anorexia, constipation, diarrhoea, nausea (after day 5 of the study) and hiccups. In addition to being a substrate for cytochrome P450 (CYP) 3A4, aprepitant is also a moderate inhibitor and inducer of this isoenzyme as well as an inducer of CYP2C9. Thus, aprepitant has the potential to interact with other agents metabolised by hepatic CYP isoenzymes. In one trial, there was a higher incidence of serious infection or febrile neutropenia in the aprepitant plus standard therapy arm than the standard therapy plus placebo arm; this was attributed to a pharmacokinetic interaction between aprepitant and dexamethasone. In subsequent trials, a modified dexamethasone regimen was used. In conclusion, when added to standard therapy (a serotonin 5-HT(3) receptor antagonist and a corticosteroid), aprepitant is effective and generally well tolerated in the prevention of CINV associated with highly emetogenic chemotherapy in adults. Despite marked advances in the prevention of CINV, standard therapy does not protect all patients. The addition of aprepitant to standard therapy provides an advance in the prevention of both acute and delayed CINV in adults with cancer.

Advances in the treatment of gynecologic cancer have extended the duration of survival of many patients. However, these patients frequently experience a variety of treatment- and disease-related side effects that diminish their quality of life (QOL) during and after treatment; among these are pain, nausea and vomiting, anemia, fatigue, peripheral neuropathy, emotional distress, and sexual dysfunction. Given the gains in survival time, patient care is being expanded to include enhancement or preservation of QOL in addition to early diagnosis and disease treatment, thus treating the whole person. In parallel with this evolution in cancer care, supportive measures are being increasingly recognized as crucial to effective patient management. This paper reviews some of the potential causes of diminished QOL in gynecologic cancer patients and basic treatment strategies for their control, with a focus on short-term QOL issues. It is important that clinicians monitor QOL during the course of the disease and its treatment, utilize procedures and therapeutic agents that take patient preferences and QOL into account, and proactively prevent and treat relevant symptoms.