Chemotherapy-induced Side Effects Research Articles

S43 - ZeOxaNMulti trial: a randomized, double-blinded, placebo-controlled trial of oral zeolite “Multizeo Med” (based on PMA-zeolite – a double activated zeolite clinoptilolite called also Panalite) to prevent chemotherapy-induced side effects, in particular peripheral neuropathy

S43 - ZeOxaNMulti trial: a randomized, double-blinded, placebo-controlled trial of oral zeolite “Multizeo Med” (based on PMA-zeolite – a double activated zeolite clinoptilolite called also Panalite) to prevent chemotherapy-induced side effects, in particular peripheral neuropathy

Intellectual development of childhood ALL patients: a multicenter longitudinal study.

In childhood acute lymphoblastic leukemia (ALL), radiotherapy for CNS prophylaxis is not used in frontline therapy anymore. Standard treatment for ALL nowadays consists of polychemotherapy. Therefore, assessment of potential chemotherapy-induced cognitive side effects becomes important. Although neurotoxicity was demonstrated in cross-sectional studies, longitudinal studies remain scarce. We evaluated intellectual development of 94 pediatric ALL patients between 1990 and 1997, diagnosed before the age of 12years, treated according to the European Organisation for Research and Treatment of Cancer Children's Leukemia Group 58881 protocol. Three assessments of the Wechsler Intelligence Scale for Children Revised were performed since diagnosis, according to age. Using repeated measures regression analysis, we investigated the effect of gender (low versus increased) risk group, parents' education, age at diagnosis, intelligence quotient (IQ) subscale (verbal (VIQ) versus performance (PIQ) intelligence), and test session. PIQ scores were lower than VIQ at baseline (-5.3 points on average, p = 0.0032), yet PIQ increased more strongly (PIQ: +3.9 points per test session; VIQ: +0.8, p = 0.0079), so this baseline difference disappeared (p = 0.0079). There were no clear effects of gender (girls: +0.6 points; p = 0.78) or risk group (low risk: +1.5 points; p = 0.49), but IQ scores were higher when one parent had followed higher education (+9.5 points, p < 0.0001). Finally, diagnosis at younger age predicted lower IQ scores (-1.3 points per year, p = 0.0009). Given that IQ scores did not decline, our findings demonstrate a stable pattern. However, the lower PIQ scores at baseline may indicate that performance functioning is vulnerable to acute neurotoxicity. Also, lower scores for younger patients highlight the stronger impact of the disease and/or treatment at younger age.Copyright © 2016 John Wiley & Sons, Ltd.

Mitochondria: Inadvertent targets in chemotherapy-induced skeletal muscle toxicity and wasting?

Chemotherapy has been associated with increased mitochondrial reactive oxygen species production, mitochondrial dysfunction and skeletal muscle atrophy leading to severe patient clinical complications including skeletal muscle fatigue, insulin resistance and wasting. The exact mechanisms behind this skeletal muscle toxicity are largely unknown, and as such co-therapies to attenuate chemotherapy-induced side effects are lacking. Here, we review the current literature describing the clinical manifestations and molecular origins of chemotherapy-induced myopathy with a focus on the mitochondria as the target organelle via which chemotherapeutic agents establish toxicity. We explore the likely mechanisms through which myopathy is induced, using the anthracycline doxorubicin, and the platinum-based alkylating agent oxaliplatin, as examples. Finally, we recommend directions for future research and outline the potential significance of these proposed directions.

A phase III study evaluating oral glutamine and transforming growth factor-beta 2 on chemotherapy-induced toxicity in patients with digestive neoplasm

BackgroundPatients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities. AimsThe primary objective of this phase III study was to evaluate the efficacy of glutamine and transforming growth factor-β2 (TGF-β2) in the prevention of grade 3–4 non-hematological toxicities induced by chemotherapy in patients with GI cancer. Patients and methodsWe designed a double-blind, randomized, controlled and multicenter trial stratified according to center, type of chemotherapy, presence of cachexia, and age. Patients were randomized to receive either Clinutren Protect® (CP) or a control isocaloric diet (without TGF-β2 or glutamine). ResultsBetween November 2007 and October 2011, 210 patients were enrolled in the study, of which 201 were included in the intention-to-treat analysis. Grade 3–4 non-hematological toxicities were not significantly different between the CP and control groups when evaluated by univariate and multivariate analyses. Likewise, no difference was observed regarding grade 3–4 hematological toxicities or reasons for treatment interruption. ConclusionThis randomized study does not support the hypothesis that oral glutamine and TGF-β2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm.

Music therapy for the reduction of chemotherapy-induced side effects in children with cancer: Two randomized controlled studies

Music therapy for the reduction of chemotherapy-induced side effects in children with cancer: Two randomized controlled studies

Integrative approach in prevention and therapy of basal cellular carcinoma by association of three actives loaded into lipid nanocarriers

Basal cell carcinoma (BCC) is one of the commonest malignancies occurred on sun-exposed skin, mainly by UV-B radiation, of lighter-skinned individuals. The aim of the present study was to develop advanced drug delivery formulations used in BCC therapy that overcomes chemotherapy-induced side-effects of skin photosensitivity by an integrative approach of nanoencapsulation in conjunction with combination therapy that uses chemotherapeutic, chemoprotective and sunscreen agents. The combination of anticancer drug together with sunscreen agent is very useful in therapy, especially for individuals who are more exposed to the sun without using a sunscreen. Nanostructured lipid carriers (NLCs) employed as drug delivery systems were co-loaded with 5-fluorouracil (5-FU), a hydrophilic chemotherapeutic drug, and ethylhexyl salicylate (EHS), a lipophilic UV-B sunscreen agent. The NLCs were developed using bioactive squalene (50.8% w/w) from amaranth seed oil as chemoprotective agent. By varying the concentrations of 5-FU and EHS, the co-loaded NLCs presented particle sizes of about 100nm, acceptable physical stability with values smaller than −25mV and appropriate entrapment efficiency that reaches values over 65% for both types of drugs. The UV-B blocking ability of EHS loaded into NLCs were influenced by the concentration of 5-FU. The amaranth oil offered a capacity of 70% in scavenging the free radicals. In vitro drug release showed that NLCs presented sustained release of 5-FU that followed the Fick’s law of diffusion.

Herbal medicines for the treatment of cancer chemotherapy-induced side effects.

Accumulating evidence suggests that Japanese herbal medicines, called Kampo, have beneficial effects on cancer chemotherapy-induced side effects. Rikkunshito ameliorates cisplatin-induced anorexia through an antagonistic effect on the 5-HT receptors and by increasing the serum ghrelin levels. Hangeshashinto improves irinotecan-induced diarrhea and chemotherapy-induced mucositis by inhibiting the activity of β-glucuronidase as well as the synthesis of prostaglandin E2. Goshajinkigan prevents oxaliplatin-induced neurotoxicity, possibly through suppressing functional alterations of the transient receptor potential channels. In this review, we will summarize the currently available literature regarding the clinical efficacy and potential mechanisms of Kampo medicines in the treatment of cancer chemotherapy-induced side effects.

Therapeutic potential of cannabinoids in counteracting chemotherapy-induced adverse effects: an exploratory review.

Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed.

The association of chemotherapy-induced toxicities with germline polymorphisms: an umbrella review of systematic reviews and meta-analyses

REVIEW QUESTION/OBJECTIVE What is the association between germline polymorphisms and chemotherapy-induced toxicities in cancer patients? INCLUSION CRITERIA Types of participants This review will consider reviews that include patients with cancer of any type, stage of progression or severity, who receive or have received chemotherapy of any variety, schedule or formulation. All ages and ethnicities will be included. Reviews that include patients treated with radiotherapy or surgery will be included if they have also received chemotherapy. Types of exposure This review will consider studies that evaluate any form of germline polymorphism (i.e. SNPs, short tandem repeats and deletions), whether detected by candidate gene analysis or GWAS. Studies that investigate race, ethnicity or sex instead of defined polymorphisms will not be included. Types of outcomes This review will consider reviews that include any chemotherapy-induced toxicities, adverse events or side effects as outcome measures. This will include those defined by any edition or volume of the common terminology criteria for adverse events or National Cancer Institute common toxicity criteria, as well as any other organizational-, national- or laboratory-specific system used to define chemotherapy-induced toxicity. Criteria for defining toxicities often assign specific grades. All grades or combinations of grades will be included. Outcomes relating to tumor or cancer response, progression free and overall survival will not be included. However, measures of treatment-related mortality will be. Treatment termination or reduction due to adverse events will also be included.

Toxgnostics: predicting and preventing chemotherapy-induced side effects.

Toxgnostics: predicting and preventing chemotherapy-induced side effects.

Toll-like receptor-5 agonist Entolimod broadens the therapeutic window of 5-fluorouracil by reducing its toxicity to normal tissues in mice

Myelosuppression and gastrointestinal damage are common side effects of cancer treatment limiting efficacy of DNA-damaging chemotherapeutic drugs. The Toll-like receptor 5 (TLR5) agonist Entolimod has demonstrated efficacy in mitigating damage to hematopoietic and gastrointestinal tissues caused by radiation. Here, using 5-Fluorouracil (5-FU) treated mice as a model of chemotherapy-induced side effects, we demonstrated significant reduction in the severity of 5-FU-induced morbidity and increased survival accompanied by the improved integrity of intestinal tissue and stimulated the restoration of hematopoiesis. Entolimod-stimulated IL-6 production was essential for Entolimod's ability to rescue mice from death caused by doses of 5-FU associated with hematopoietic failure. In contrast, IL-6 induction was not necessary for protection and restoration of drug-damaged gastrointestinal tissue by Entolimod. In a syngeneic mouse CT26 colon adenocarcinoma model, Entolimod reduced the systemic toxicity of 5-FU, but did not reduce its antitumor efficacy indicating that the protective effect of Entolimod was selective for normal, non-tumor, tissues. These results suggest that Entolimod has clinical potential to broaden the therapeutic window of genotoxic anticancer drugs by reducing their associated hematopoietic and gastrointestinal toxicities.

The traditional Chinese medical compound Rocaglamide protects nonmalignant primary cells from DNA damage-induced toxicity by inhibition of p53 expression

One of the main obstacles of conventional anticancer therapy is the toxicity of chemotherapeutics to normal tissues. So far, clinical approaches that aim to specifically reduce chemotherapy-mediated toxicities are rare. Recently, a number of studies have demonstrated that herbal extracts derived from traditional Chinese medicine (TCM) may reduce chemotherapy-induced side effects. Thus, we screened a panel of published cancer-inhibiting TCM compounds for their chemoprotective potential and identified the phytochemical Rocaglamide (Roc-A) as a candidate. We show that Roc-A significantly reduces apoptotic cell death induced by DNA-damaging anticancer drugs in primary human and murine cells. Investigation of the molecular mechanism of Roc-A-mediated protection revealed that Roc-A specifically blocks DNA damage-induced upregulation of the transcription factor p53 by inhibiting its protein synthesis. The essential role of p53 in Roc-A-mediated protection was confirmed by siRNA knockdown of p53 and by comparison of the effects of Roc-A on chemoprotection of splenocytes isolated from wild-type and p53-deficient mice. Importantly, Roc-A did not protect p53-deficient or -mutated cancer cells. Our data suggest that Roc-A may be used as an adjuvant to reduce the side effects of chemotherapy in patients with p53-deficient or -mutated tumors.

Administration Of E-Selectin Antagonist GMI-1271 Improves Survival After High-Dose Chemotherapy By Alleviating Mucositis and Accelerating Neutrophil Recovery

Cytotoxic chemotherapies used to treat acute leukemia and high-grade lymphoma target rapidly-dividing cells including the malignant cells but also normal HSC needed to replenish the blood and immune system, as well as mucosal cells lining the respiratory and gastrointestinal tracts. Consequences include therapy-induced mucositis (providing a portal of entry for bacteria) and neutropenia leading to increased morbidity and potentially life-threatening infections. In acute myeloid leukemia and high-grade lymphoma patients, treatment-related mortality can reach 20% (Elmaagacli, BMT, 2007).We now report a novel therapy (therapeutic blockade of E-selectin) that may enhance survival after repeated rounds of high-dose chemotherapy. In mice we find the mechanism contributing to this enhanced survival to be a combination of accelerated neutrophil recovery and a dramatic reduction in therapy-related weight loss and intestinal mucositis when E-selectin is therapeutically blocked or genetically-deleted.Our studies were performed using two treatment regimens (chemotherapy or radiation). For chemotherapy, cohorts of mice received repeated rounds of the anti-metabolite, 5-fluorouracil (5-FU) at a dose of 150mg/kg every 10 days without prophylactic antibiotic support. Using this regime, 80% of E-selectin gene-deleted mice (E-/-) survived >6 weeks. In sharp contrast all wild-type mice died (p<0.05). To determine whether febrile neutropenia was potentially involved, blood was collected for analysis on the 10th day following each round of treatment, just prior to the administration of the next round of 5-FU. After 4 rounds of chemotherapy E-/- mice had recovered acceptable neutrophil counts (n=10). In contrast, only 5 of 10 wild-type mice had recovered from therapy-induced neutropenia. Most of those that could not subsequently died.Deletion of the E-selectin gene also prevented therapy-induced weight loss (from 16% average weight loss in wild-type mice, to only 2% in E-/- mice after 2 rounds 5-FU, p<0.05) which was completely unanticipated. To investigate this further, cohorts of mice were administered 5-FU as described above for histological scoring of intestinal mucositis. To our surprise, we found that deletion of the E-selectin gene almost completely alleviated chemotherapy-induced mucositis. In sharp contrast, intestines of wild-type mice showed extensive ulceration and villous loss with inflammatory infiltrates occurring at the same time as neutropenia – very likely contributing to their death. Moreover we found E-selectin was up-regulated 10-fold in the intestines following chemotherapy or radiation damage, which we hypothesis is critical for recruitment of inflammatory cells to the mucosa. Indeed by immunohistology and flow cytometry, migration of F4/80+ macrophages to 5-FU damaged intestines was increased 7-10-fold in wild-type mice but completely absent in E-/- mice. Similar results were also observed following 8.0 Gy total body irradiation.Therapy-induced mucositis is greatly exacerbated by a wave of secondary inflammation following initial direct damage. We found administration of the selective E-selectin antagonist GMI-1271 (20 mg/kg bi-daily) for 5 days following each round of chemotherapy enhanced neutrophil recovery and similarly protected mice from weight loss and mucositis following chemotherapy. Importantly the administration of GMI-1271 effectively blocked secondary migration of inflammatory F4/80+ Ly-6C+ macrophages to intestines of mice following chemotherapy or irradiation.In conclusion, our results suggest that inflammatory macrophages play a major role in chemotherapy-induced mucositis and are recruited to damaged intestine following E-selectin up-regulation. Importantly there is no current highly-effective treatment to prevent mucositis. Therapeutic blockade of E-selectin by administration of GMI-1271 at the same time as chemotherapy represents a potential effective and novel therapy to block recruitment of inflammatory macrophages to damaged mucosa whilst also enhancing neutrophil recovery, thus protecting patients from two chemotherapy-induced side-effects. Therapeutic blockade of E-selectin should provide an opportunity for improved completion rates of toxic chemotherapy or radiotherapy regimes and reduce therapy-related morbidity and mortality. Disclosures:Magnani:GlycoMimetics, Inc.: Employment, Equity Ownership.

Neurotoxicity of cancer chemotherapy.

There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causal mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.

A genetic variant of 5-hydroxytryptamine receptor 3C (HTR3C): A novel link to chemotherapy-induced side effects.

9630 Background: Symptom clusters are defined as three or more concurrent symptoms that are related to each other. Clusters may stem from common physiological mechanisms and may better represent adverse effects to chemotherapy compared to individual symptoms. We aimed to identify association between the experience of symptom clusters and specific genetic alterations. Methods: Study population consisted of 108 breast cancer patients who received over two cycles of adjuvant doxorubicin and cyclophosphamide (AC) treatment at the oncology institute of the Sheba Medical Center. Participants completed the Memorial Symptom Assessment Scale, the Lee Fatigue Scale and the Center for Epidemiological Studies Depression Scale. Hierarchical cluster analysis was used to identify patients' subgroups based on their symptom experience. For the genetic analyses, DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) of candidate genes were tested using restriction endonuclease assays. Results: Two distinct subgroups were identified based on severity of fatigue, depression, nausea, and change in food tastes: "all high" (n=79) and "all low" (n=29) level of all symptoms. As patients did not have active cancer, symptoms were attributed solely to chemotherapy. A genetic variant of HTR3C (rs6766410) results in a substitution of asparagine to lysine (N163K) may be associated with nausea and vomiting. We tested the association between this variant and symptom score. 51 of 75 (68%) patients with high symptom score harbored the variant allele, compared to 13 of 28 (46%) of those with low symptom score (p=0.038). Conclusions: Analysis of genetic background of clusters, rather than for individual symptoms, represents a novel approach for the study of chemotherapy-induced side effects. This approach enabled the identification of HTR3C variant as a possible mediator of side effects following treatment with AC. Discovering the genetic basis of symptom clusters may lead to the development of novel diagnostic and therapeutic modalities able to improve symptom management. This may translate to improved outcome among chemotherapy-treated cancer patients.

Predicting risk of chemotherapy-induced side effects in patients with colon cancer with single-nucleotide polymorphism (SNP) Bayesian networks (BNs).

344 Background: Patients receiving standard chemotherapy for colon cancer are at significant, but unequal, risk for development of treatment-induced side effects. Currently, there is no accurate way to identify these risks for individual patients. This study adopted a novel approach to creating a risk prediction model for chemotherapy-induced side effects through the development of clusters of SNPs defined by BNs. It was designed to assess the feasibility of identifying SNP-BNs that could accurately predict the risk for 6 common, and often debilitating, side effects: chemotherapy-induced nausea/vomiting (CINV), diarrhea, oral mucositis (OM), cognitive dysfunction (CD), peripheral neuropathy (PN), and fatigue. Methods: Patients (n=57) with colon cancer who received at least 3 cycles of FOLFOX6 +/- bevacizumab (along with standard supportive care strategies) were enrolled. Saliva samples were collected, DNA was isolated, and SNPs were analyzed on Illumina Omni microarrays (2.5 x 106 SNPs). Side effects under consideration were observed using Patient Care Monitor, a validated patient-reported symptom assessment instrument. BNs were developed for each of the 6 side effects and cross-validated using robust statistical analyses. Results: The percentage of patients who experienced moderate-to-severe side effects was notable despite supportive care measures. These included the following: CINV (32%), diarrhea (16%), OM (26%), CD (21%), PN (26%), and fatigue (56%). SNP-BNs were defined for each of the 6 side effects and were found to predict risk with a high degree of accuracy (&gt;90%) and receiver operating characteristic (ROC) curves (&gt;0.920). Conclusions: This study calls attention to the fact that treatment-related side effects persist in patients receiving FOLFOX6 +/- bevacizumab for colon cancer. SNP-BNs were identified that could accurately predict 6 of the most common treatment-related side effects. This genomic-based tool has the potential to offer clinicians accurate and actionable information for individualizing a patient’s cancer care plan.

The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care — an observational analysis on non-small-cell lung cancer patients

To evaluate frequency and severity of adverse drug reactions (ADRs) and its economic consequences after standard dose (immuno-)chemotherapy (CT) of non-small-cell lung cancer (NSCLC). Subanalysis of a prospective, multicentre, longitudinal, observational cohort study; data were collected from patient interviews and pre-planned chart reviews. Costs were aggregated per CT line and presented from provider perspective. A total of 120 consecutive NSCLC patients (mean age, 63.0 ± 8.4 (SD) years; men, 64.2%; ECOG (Eastern Cooperative Oncology Group) performance status <2, 84.3%; tumour stage III/IV, 85%; history of comorbidity, 93.3%) receiving 130 CT lines were evaluated. 80% of CT lines were associated with grade 3 or 4 ADRs, 22.3% developed potential life-threatening complications, 77.7% were associated with at least one hospital stay (inpatient, 63.9%; outpatient/day clinic 39.2%, ICU 6.9%), with a mean cumulative number of 12.8 (±14.0 SD) hospital days. Mean (median) toxicity management costs per CT line (TMC-TL) amounted to €3,366 (€1,406) and were found to be higher for first-line compared to second-line treatment: €3,677 (€1,599) vs. €2,475 (€518). TMC-TL were particularly high in CT lines with ICU care €12,207 (€9,960). Eight out of 11 ICU stays were associated with grade 3 or 4 infections. Nine CT lines with ICU care accounted for 25% of total expenses (€109,861 out of €437,580). In first-line NSCLC treatment, in particular, CT toxicity management is expensive. Asymmetric cost distribution seems to be triggered by infection associated ICU care. Its avoidance should reduce patients' clinical burden and have considerable economic implications. Nevertheless, comparative observational studies have to confirm estimated savings.

Colon Cancer Reversed by Phyto-Nutritional Therapy: A Case Study

Colorectal cancer is the second most common cancer in Malaysia and up to 80% of its patients seek complementary therapies. Globally, up to 95% of cancer patient use adjunct therapies to reduce chemotherapy-induced side-effects. Morgan et al . (2004) had showed that conventional treatment for colon cancer produced minimal results. The vast majority of cancer survivors admitted to using dietary supplements and herbs after their cancer diagnosis. Current treatment seems to pay more attention to cancer as a disease rather than meeting the physiological needs of the patient. Nutritional therapy should be individually tailored since dietary deficiency is multifactorial and the tumor burden for each patient is different. Cancer is a metabolic disorder and colon cancer is strongly associated with advancing age, dietary and lifestyle habits. Up to 90% of all cancers might be prevented with proper nutrition since one-third of overall cancer deaths are linked to malnutrition. This case study shows how a late stage colon adenocarcinoma might be completely reversed by evidence-based phyto-nutritional therapy combined with some lifestyle modifications. The cancer apoptotic properties of this natural protocol warrant further investigation involving a higher number of patients with similar conditions

Abstract P1-15-12: Single Nucleotide Polymorphism (SNP) Bayesian networks (BNs) Predict Risk of Chemotherapy-Induced Side Effects in Patients with Breast Cancer Receiving Dose Dense (DD) Doxorubicin/Cyclophosphamide Plus Paclitaxel (AC+T)

Abstract Background: Despite advances in supportive care, patients undergoing standard chemotherapy for breast cancer are at significant, but unequal, risk for the development of treatment-induced side effects. Current methods for predicting risk are inconsistent and unreliable. Because the pathobiology of many side effects are regulated by the synergistic interaction of simultaneously expressed genes, we reasoned that a novel approach to risk prediction could be achieved by the development of clusters of SNPs defined by BNs. The present study was designed to assess the feasibility of identifying BNs that were associated with regimen-related diarrhea, oral mucositis, nausea and vomiting, fatigue, cognitive dysfunction and neuropathy in patients with breast cancer treated with dose-dense AC+T. The primary endpoint was an area under the receiver operating characteristic curve (aROC) &amp;gt;0.80. Methods: After informed consent, 78 patients with breast cancer who had received at least 3 cycles of (DD) AC+T were enrolled and saliva samples were collected. Salivary DNA was isolated and analyzed on Illumina Omni microarrays (2.5 × 106 SNPs). Standard supportive therapy for prevention and management of side effects was provided. The frequency and severity of diarrhea, oral mucositis, fatigue, cognitive dysfunction, neuropathy&amp;lt;INS dateTime=2012-09-25T18:35 cite=“mailto:CJordan”&amp;gt;,&amp;lt;/INS&amp;gt; and nausea and vomiting were determined using Patient Care Monitor©, a validated patient-reported symptom assessment instrument. BNs were developed for each of the six side effects using Bayesian methods including ten-fold internal cross-validation. Results: The incidence of clinically significant side effects was higher than anticipated by the literature and are reported in Table 1 along with the accuracy and aROC. Conclusions: We identified SNP-BNs associated with moderate to severe common side effects of AC+T regimens used to treated breast cancer. These BNs, sourced from salivary SNPs, should provide &amp;lt;/DEL&amp;gt; clinicians with accurate actionable information which predicts side effect risk for patients who are scheduled to receive dose-dense doxorubicin/cyclophosphamide and paclitaxel for the treatment of breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-12.

Effect of platinum-containing chemotherapy on olfactory, gustatory, and hearing function in ovarian cancer patients

Most patients with epithelial ovarian cancer have a poor overall prognosis. Therefore, one of the main therapeutic aims after cytoreductive surgery for these patients is to identify, delay and relieve chemotherapy-induced side effects and optimise the quality of life, especially after first-line therapy. Twelve ovarian cancer patients undergoing carboplatinum-containing chemotherapy were assessed using validated tests for olfactory, gustatory, and hearing functions before, during, immediately after, and 3 months after chemotherapy. All chemosensory functions decreased during and after carboplatinum-containing chemotherapy, but recovered 3 months after treatment ended. For olfaction, this decrease was significant, affecting odour identification minimally, and odour threshold the most. For taste, the decrease was not significant, but could be observed in total scores and in each quality (sweet, sour, salty, and bitter). For hearing, the decrease was not significant, but a recovery of the deep and middle frequencies was clearly evident 3 months after chemotherapy. Patients must be informed about transient declines in chemosensory functions during chemotherapy. Symptomatic relief provided by the use of more spices, a small amount of glutamate, or additional flavouring might help to compensate for decreased functions during chemotherapy and increase patient quality of life.