Explore the vast range of titles available.

Purpose The aim of this study was to review the available literature and define clinical practice guidelines for the use of agents for the prevention and treatment of gastrointestinal mucositis. Methods A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. Results A total of 251 clinical studies across 29 interventions were examined. Panel members were able to make one new evidence-based negative recommendation; two new evidence-based suggestions, and one evidence-based change from previous guidelines. Firstly, the panel recommends against the use of misoprostol suppositories for the prevention of acute radiation-induced proctitis. Secondly, the panel suggests probiotic treatment containing Lactobacillus spp., may be beneficial for prevention of chemotherapy and radiotherapy-induced diarrhea in patients with malignancies of the pelvic region. Thirdly, the panel suggests the use of hyperbaric oxygen as an effective means in treating radiation-induced proctitis. Finally, new evidence has emerged which is in conflict with our previous guideline surrounding the use of systemic glutamine, meaning that the panel is unable to form a guideline. No guideline was possible for any other agent, due to inadequate and/or conflicting evidence. Conclusions This updated review of the literature has allowed new recommendations and suggestions for clinical practice to be reached. This highlights the importance of regular updates.

Purpose Anthracyclines (including doxorubicin) are still the backbone of commonly used breast cancer chemotherapy regimens. Despite increasing use of doxorubicin and cyclophosphamide (AC) combinations for treating breast cancer, their potential to cause adverse skeletal effects remains unclear. Methods This study examined the effects of treatments with the AC regimen on bone and bone marrow in adult female rats. Results AC treatment for four cycles (weekly intravenous injection of 2 mg/kg doxorubicin and 20 mg/kg cyclophosphamide) resulted in a reduced volume of trabecular bone at the metaphysis, which was associated with reduced serum levels of 25-hydroxy vitamin D3 and alkaline phosphatase. Reductions in densities of osteocytes and bone lining cells were also observed. In addition, bone marrow was severely damaged, including a severe reduction in bone marrow cellularity and an increase in marrow adipocyte content. Accompanying these changes, there were increases in mRNA expression of adipogenesis regulatory genes (PPARγ and FABP4) and an inflammatory cytokine (TNFα) in metaphysis bone and bone marrow. Conclusions This study indicates that AC chemotherapy may induce some bone loss, due to reduced bone formation, and bone marrow damage, due to increased marrow adiposity. Preventive strategies for preserving the bone and bone marrow microenvironment during anthracycline chemotherapy warrant further investigation.

Purpose A common side effect of chemotherapy treatment is diarrhoea. Unfortunately, the underlying mechanisms of chemotherapy-induced diarrhoea (CD) are poorly understood. We aimed to determine if faecal microbes of CD patients were displaced, if faecal calprotectin increased during CD and if there were alterations in circulating matrix metalloproteinases, nuclear factor kappa B (NF-κB), IL-1β and TNF. Patients and methods Twenty-six cancer patients receiving chemotherapy were enrolled and requested to provide stool samples and blood samples at various times during their chemotherapy cycle. Stool samples were analysed using conventional culture techniques and qRT-PCR. ELISA kits determined faecal calprotectin levels, levels of circulating matrix metalloproteinases and circulating NF-κB, IL-1β and TNF. Results The majority of patients with CD showed decreases in Lactobacillus spp., Bifidobacterium spp., Bacteroides spp. and Enterococcus spp. Increases were observed in Escherichia coli and Staphylococcus spp. Methanogenic archaea were also quantified, with all patients except one showing a decrease. Faecal calprotectin levels were increased in 81.25 % of patients with CD. Circulating MMP-3 and MMP-9 significantly increased following chemotherapy. Circulating levels of NF-κB, IL-1β and TNF were increased following chemotherapy, although this did not reach significance. Conclusions We demonstrated that CD is associated with marked changes in intestinal microflora, methanogenic archaea, matrix metalloproteinase and serum levels of NF-κB, IL-1β and TNF. These changes may result in diminished bacterial functions within the gut, altering gut function and initiating intestinal damage, resulting in the onset of diarrhoea. More importantly, these changes may provide clinicians with a possible new target for biomarkers of toxicity.

Purpose The pathobiology of alimentary tract (AT) mucositis is complex and there is limited information about the events which lead to the mucosal damage that occurs during cancer treatment. Various transcription factors and proinflammatory cytokines are thought to play important roles in pathogenesis of mucositis. The aim of this study was to determine the expression of nuclear factor-κB (NF-κB), tumor necrosis factor (TNF) and interleukins-1β (IL-1β) and -6 (IL-6) in the AT following the administration of the chemotherapeutic agent irinotecan. Methods Eighty-one female dark Agouti rats were assigned to either control or experimental groups according to a specific time point. Following administration of irinotecan, rats were monitored for the development of diarrhoea. The rats were killed at times ranging from 30 min to 72 h after administration of irinotecan. Oral mucosa, jejunum and colon were collected and standard immunohistochemical techniques were used to identify NF-κB, TNF, IL-1β and IL-6 within the tissues. Sections were also stained with haematoxylin and eosin for histological examination. Results Irinotecan caused mild to moderate diarrhoea in a proportion of the rats that received the drug. Altered histological features of all tissues from rats administered irinotecan were observed which included epithelial atrophy in the oral mucosa, reduction of villus height and crypt length in the jejunum and a reduction in crypt length in the colon. Tissue staining for NF-κB, TNF and IL-1β and IL-6 peaked at between 2 and 12 h in the tissues examined. Conclusions This is the first study to demonstrate histological and immunohistochemical evidence of changes occurring concurrently in different sites of the AT following chemotherapy. The results of the study provide further evidence for the role of NF-κB and associated pro-inflammatory cytokines in the pathobiology of AT mucositis. The presence of these factors in tissues from different sites of the AT also suggests that there may be a common pathway along the entire AT causing mucositis following irinotecan administration.

This Review article approaches the area of targeted therapies from two angles: efficacy and side effects. The authors outline the successes that have been achieved in treating cancer with targeted therapies and also discuss the pitfalls and quality of life issues that still need to be addressed. The advent of targeted anticancer therapies over the past few decades has reinvigorated the field of cancer therapeutics, with the promise of increased cancer cure rates accompanied by decreased toxicity. But, has that promise been fulfilled? The short answer is definitely 'no', both because of disappointing tumor responses and unexpectedly high toxicity, as well as the extremely high financial cost of these agents. However, failing to completely fulfill initial promise does not mean that targeted therapies should be abandoned. Increased progression-free survival might ultimately lead to increased overall survival, and targeted therapies have changed the course of cancers such as breast, lung and renal. Therefore, we would argue that despite some disappointments, targeted therapies have a vital role in future cancer treatment. This Review will discuss the positives and negatives of targeted agents, and propose a way to optimize their use and development to ensure proper personalized cancer medicine that tailors not only the anticancer treatment, but also the antitoxicity strategies, to achieve the best outcome for the patient in terms of both quality and quantity of life. Key Points Incremental benefits of cancer treatments over the past few decades have substantially improved survival and mortality rates for many cancer types; however, treatment-related toxicity remains a large problem Targeted therapies have contributed considerably to anticancer benefits; however, co-expression of many targets on normal cells means that toxicity is still a problem Despite toxicities and costs, targeted therapies have such a positive impact on progression-free survival and overall cancer survival, as well as quality of life, that their continued use is justified To further support use of targeted therapies, more research needs to be done on toxicity profiling, toxicity mechanisms and long-term follow-up analyses More research into targeted agents and their toxicities will further contribute to the repertoire of anticancer treatments, building on past success Successful cancer treatment in the future will be multidisciplinary, allowing for maximization of tumor control with concomitant minimization of adverse effects and cost of treatment

Purpose This paper describes the incidence of chemotherapy-induced nausea and vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. Methods Sequential adult patients naïve to chemotherapy and scheduled to receive at least two cycles of single-day HEC or MEC were enrolled in this prospective observational study. Patients completed the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool on post-chemotherapy days 2 and 6 to record acute-phase (first 24 h) and delayed-phase (days 2–5) CINV. Results There were 648 evaluable patients (318 HEC, 330 MEC) from Australia ( n  = 74), China (153), India (88), Singapore (57), South Korea (151), and Taiwan (125). Mean (SD) patient age was 56 (12) and 58 % of patients were women; the most common primary cancers were breast (27 %), lung (22 %), and colon (20 %). Overall in cycle 1, complete response (no emesis or rescue antiemetics) was recorded by 69 % (95 % confidence interval (CI), 66–73) of all evaluable patients, with country percentages ranging from 55 to 78 % ( p  < 0.001). After HEC, no emesis was recorded by 75 % and no nausea by 38 % of patients. After MEC, 80 % had no emesis and 50 % no nausea. Acute-phase CINV was better controlled than delayed-phase CINV, and the control of nausea was the lowest of any CINV measure in all phases. In a CINV perception survey, physicians tended to overestimate emesis rate and underestimate nausea rate. Conclusions CINV remains a substantial problem, and country-specific information about CINV can be useful in developing strategies to improve outcomes for patients undergoing chemotherapy.

Purpose Alimentary tract (AT) mucositis is a serious problem complicating cancer treatment, however, its pathobiology remains incompletely understood. Nuclear factor-κB (NF-κB) and pro-inflammatory cytokines are considered to have important roles in its development. This has been previously demonstrated in different sites of the AT following administration of irinotecan in an animal model using the Dark Agouti rat. The aim of the present study was to determine whether the changes that occur in the AT are affected by the type of mucotoxic drug. Methods Female DA rats were given a single dose of either methotrexate (1.5 mg/kg intramuscularly) or 5-fluorouracil (150 mg/kg intraperitoneally). Rats were killed at 30, 60, 90 min, 2, 6, 12, 24, 48 and 72 h. Control rats received no treatment. Samples of oral mucosa, jejunum and colon were collected. Haematoxylin and eosin stained sections were examined with respect to histological evidence of damage and standard immunohistochemical techniques were used to demonstrate tissue expression of NF-κB, TNF, IL-1β and IL-6. Results Both MTX and 5-FU administration caused histological evidence of tissue damage in the AT as well as changes in tissue expression of NF-κB and specific pro-inflammatory cytokines. This study, however, demonstrated that there were differences in the timing of histological changes as well as the timing and intensity of pro-inflammatory cytokine tissue expression caused by the different drugs. Conclusions The results from this study suggest that there are differences in the mucositis pathobiology caused by different drugs. This may have important ramifications for the management of mucositis particularly with respect to the development of treatment regimens for mucositis. Further investigations are required to determine the exact pathways that lead to damage caused by the different drugs.

The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among breast cancer patients. Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) combination therapy is now one of the preferred regimens for treating node-positive breast cancer due to better survival with less toxicity involved. Despite the increasing use of CEF, its potential in causing adverse skeletal effects remains unclear. Using a mature female rat model mimicking the clinical setting, this study examined the effects of CEF treatment on bone and bone marrow in long bones. Following six cycles of CEF treatment (weekly intravenous injections of cyclophosphamide at 10 mg/kg, epirubicin at 2.5 mg/kg and 5-flurouracil at 10 mg/kg), a significant reduction in trabecular bone volume was observed at the metaphysis, which was associated with a reduced serum level of bone formation marker alkaline phosphatase (ALP), increased trends of osteoclast density and osteoclast area at the metaphysis, as well as an increased size of osteoclasts being formed from the bone marrow cells ex vivo. Moreover, a severe reduction of bone marrow cellularity was observed following CEF treatment, which was accompanied by an increase in marrow adipose tissue volume. This increase in marrow adiposity was associated with an expansion in adipocyte size but not in marrow adipocyte density. Overall, this study indicates that six cycles of CEF chemotherapy may induce some bone loss and severe bone marrow damage. Mechanisms for CEF-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigation.

Purpose Some patients experience nausea and/or vomiting (NV) before receipt of chemotherapy. Our objective was to evaluate the impact of prior chemotherapy-induced NV (CINV) on the incidence of anticipatory NV in later cycles. Methods This multicenter, prospective non-interventional study enrolled chemotherapy-naïve adults scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC) for cancer in six Asia Pacific countries, excluding those with emesis within 24 h before cycle 1 chemotherapy. On day 1 before chemotherapy, patients answered four questions regarding emesis in the past 24 h, nausea, expectation of post-chemotherapy nausea, and anxiety in the past 24 h, the latter three scored from 0–10 (none–maximum). Multivariate logistic regression was used to assess the impact of prior CINV on anticipatory NV in cycles 2 and 3. Results Five hundred ninety-eight patients (59 % female) were evaluable in cycle 2 (49 % HEC, 51 % MEC). The incidence of anticipatory emesis was low before cycles 2 and 3 (1.5–2.3 %). The incidence of clinically significant anticipatory nausea (score of ≥3) was 4.8, 7.9, and 8.3 % before cycles 1, 2, and 3, respectively, with adjusted odds ratio (OR), 3.95 (95 % confidence interval (CI), 2.23–7.00; p  < 0.001) for patients with clinically significant nausea in prior cycles, compared with none. The adjusted ORs for other anticipatory NV endpoints ranged from 4.54–4.74 for patients with prior CINV. The occurrence of clinically significant anxiety in the prior cycle also resulted in a significantly increased likelihood of anticipatory nausea. Conclusions These findings highlight the importance of preventing CINV in cycle 1 to reduce anticipatory NV in subsequent cycles.

Purpose This paper reports prescribing patterns for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. Methods In a prospective noninterventional study, 31 sites in Australia, China, India, Singapore, South Korea, and Taiwan recorded details of CINV prophylaxis for the acute phase (first 24 h) and delayed phase (days 2–5) after single-day HEC or MEC for adult patients. Additional information on CINV prophylactic medications was collected from 6-day patient diaries. Primary antiemetic therapies were defined as corticosteroids, the 5-hydroxytryptamine-3 receptor antagonists (5HT3-RAs), and neurokinin-1 receptor antagonists (NK1-RAs). Results Evaluable patients in cycle 1 numbered 648 (318 [49 %] HEC and 330 [51 %] MEC) of mean (SD) age of 56 (12) years, including 58 % women. For the acute phase after HEC, overall (and country range), 96 % (91–100 %) of patients received a 5HT3-RA, 87 % (70–100 %) a corticosteroid, and 43 % (0–91 %) an NK1-RA. CINV prophylaxis for the HEC delayed phase was more variable: including 22 % (7–65 %) 5HT3-RA, 52 % (12–93 %) corticosteroid, and 46 % (0–88 %) NK1-RA. For the MEC acute phase, 97 % (87–100 %) of patients received 5HT3-RA and 86 % (73–97 %) a corticosteroid. For the MEC delayed phase, 201 patients (61 %) received a primary antiemetic, including 5HT3-RA (41 %), corticosteroid (37 %), and/or NK1-RA (4 %). Conclusions The 5HT3-RAs were prescribed consistently in all countries, while prescribing of other antiemetic therapies was variable, and corticosteroids were under-prescribed for CINV prophylaxis, particularly in the delayed phase.