Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients.

PURPOSE: Despite the widespread use of antiemetics, nausea continues to be reported by over 70% of patients receiving chemotherapy. METHODS: In this double blind, multicenter trial, we randomly assigned 744 cancer patients to four arms: 1) placebo, 2) 0.5 g ginger, 3) 1.0 g ginger, or 4) 1.5 g ginger. Nausea occurrence and severity were assessed at a baseline cycle and the two following cycles during which patients were taking their assigned study medication. All patients received a 5-HT(3) receptor antagonist antiemetic on Day 1 of all cycles. Patients took three capsules of ginger (250 mg) or placebo twice daily for 6 days starting 3 days before the first day of chemotherapy. Patients reported the severity of nausea on a 7-point rating scale ("1" = "Not at all Nauseated" and "7" = "Extremely Nauseated") for Days 1-4 of each cycle. The primary outcomes were to determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea on Day 1 of chemotherapy. RESULTS: A total of 576 patients were included in final analysis (91% female, mean age = 53). Mixed model analyses demonstrated that all doses of ginger significantly reduced acute nausea severity compared to placebo on Day 1 of chemotherapy (p = 0.003). The largest reduction in nausea intensity occurred with 0.5 g and 1.0 g of ginger (p = 0.017 and p = 0.036, respectively). Anticipatory nausea was a key factor in acute chemotherapy-induced nausea (p < 0.0001). CONCLUSIONS: Ginger supplementation at a daily dose of 0.5 g-1.0 g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients.

A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.

Community-based clinical oncology research trials for cancer-related fatigue.

Cancer-related fatigue (CRF) is a highly prevalent and debilitating symptom experienced by most cancer patients during, and often for considerable periods after, treatment. This symptom affects patients' overall quality of life and is characterized by persistent exhaustion and a decreased capacity to perform daily social and cognitive tasks. CRF is also one of the most commonly reported side effects of cancer and cancer treatments, including surgery, chemotherapy, radiotherapy, hormonal therapy, and biologic response modification therapy. Pharmacologic methods for treating CRF are not always reliable, and many patients continue to experience this symptom following pharmacologic interventions. Managing CRF is of importance to oncology researchers and clinical service providers. As of March 15, 2006, 76 National Institutes of Health sponsored studies examining CRF were actively recruiting subjects, and 15% of these studies were being conducted through the National Cancer Institute (NCI) Community Clinical Oncology Program (CCOP). This article will provide a description of-the NCI CCOP, its functions, and a brief overview of ongoing research on CRF both at our institution and other locations across the United States.

Fatigue and depression in cancer patients undergoing chemotherapy: an emotion approach.

Fatigue and depressive symptoms are common in cancer patients, but the nature of the relationship between the two remains unclear. We examined the degree to which two dimensions of emotion assessed as psychological factors (i.e., arousal and valence) predicted changes in fatigue and depressive symptoms over four cycles of chemotherapy in cancer patients who participated in a randomized clinical trial. Among 549 patients enrolled in the study, 525 provided data from a minimum of two treatments and were included in the multilevel modeling analyses. Multilevel models were used to identify significant predictors of initial levels and changes of fatigue and depressive symptoms and to determine the relationship between fatigue and depressive symptoms independent of other predictors proposed in this study. Multiple factors, including age, gender, and cancer site, predicted the initial levels. More importantly, the two dimensions of psychological factors significantly predicted changes in fatigue and depressive symptoms, in similar patterns but to different degrees. Specifically, changes in fatigue depended more on the valence dimension, whereas changes in depressive symptoms depended on both the valence and arousal dimensions. Theoretical and practical implications of the current findings are discussed and suggestions for interventions to alleviate fatigue and depressive symptoms in cancer patients are proposed.

Exploratory analysis of the usefulness of acupressure bands when severe chemotherapy-related nausea is expected.

The present study examines the efficacy of acupressure wristbands, compared with standard care alone and acustimulation wristbands, in preventing severe nausea among 86 breast cancer patients receiving doxorubicin-based chemotherapy who were at high risk of experiencing severe nausea following treatment. Significant differences in the proportion of patients who reported severe nausea were observed across three conditions (standard care, standard care with acupressure bands, and standard care with an acustimulation band). The proportion of patients in the acupressure band group who reported severe nausea following their chemotherapy treatment (41%) was significantly less than that of the standard care group (68%) and the acustimulation band group (73%). Overall, these findings showed that acupressure wristbands were efficacious and may be an appropriate form of adjuvant therapy for nausea management for breast cancer patients, especially those who are most at risk for experiencing severe nausea following chemotherapy treatment.

Occurrence, severity, and longitudinal course of twelve common symptoms in 1129 consecutive patients during radiotherapy for cancer.

Little is known about the frequency, severity, and course of symptoms experienced by patients receiving radiotherapy (RT). For this descriptive study, 1129 patients with a variety of cancer diagnoses completed a 12-item Symptom Inventory (SI) at the start of RT; 419 of these patients also completed the SI weekly for an additional 4 weeks (five data points). Eighty-four percent of the 1129 patients were already experiencing symptoms when treatment began. All symptoms significantly increased in frequency over a typical 5 week RT course (all Ps<0.001). Skin problems showed the largest increase. The most common symptoms (fatigue, drowsiness, and sleep problems) were also the most severe. Female patients and patients younger than the median age (59 years) reported significantly more symptoms than males and those 59 years or older. Symptom frequency and severity varied significantly by cancer diagnosis. Improved understanding about the time course and dose response of radiation-induced toxicity will permit more accurate presentation of side effect risk at the time patient consent is obtained.

5-Hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomised controlled trial.

BACKGROUND: Despite widespread use of short-acting antagonists for the 5-hydroxytryptamine (5-HT) receptor, about 50% of patients given moderately emetogenic chemotherapy have delayed nausea. We aimed to assess whether a 5-HT-receptor antagonist was more effective than was prochlorperazine for control of delayed nausea and delayed vomiting caused by doxorubicin. METHODS: 691 patients who previously had not had chemotherapy and who were scheduled to receive doxorubicin were given a short-acting 5-HT-receptor antagonist and dexamethasone before doxorubicin (day 1), and were randomly assigned to one of three regimens for days 2 and 3: 10 mg prochlorperazine taken orally every 8 h; any first-generation 5-HT-receptor antagonist (except palonosetron) taken as standard dose intravenously or orally; or 10 mg prochlorperazine taken as needed. Nausea and vomiting were assessed by use of a home record. The primary endpoint was mean severity of delayed nausea. The secondary endpoint was quality of life. Analyses were done by intention to treat. FINDINGS: 519 (77%) of the 671 evaluable patients had delayed nausea, with a mean severity of 3.33 (95% CI 3.22-3.44). 161 (71%) of 226 patients assigned prochlorperazine every 8 h reported delayed nausea (mean severity 3.37 [3.16-3.58]), as did 179 (79%) of 226 patients assigned 5-HT-receptor antagonists (3.29 [3.09-3.48]) and 179 (82%) of 219 patients assigned prochlorperazine as needed (3.33 [3.15-3.50]); groups did not differ in mean severity (p=0.853, one-way ANOVA). Patients allocated prochlorperazine every 8 h had less delayed nausea than did those allocated 5-HT-receptor antagonists (p=0.05, t test) and those allocated prochlorperazine as needed (p=0.009, t test). INTERPRETATION: Short-acting 5-HT-receptor antagonists are no better than is prochlorperazine in control of delayed nausea caused by doxorubicin. Although fewer patients taking prochlorperazine report delayed nausea, the proportion was unacceptably high.

Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial.

BACKGROUND: Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer. METHODS: 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat. FINDINGS: Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity. INTERPRETATION: Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer.

Frequency, severity, clinical course, and correlates of fatigue in 372 patients during 5 weeks of radiotherapy for cancer.

BACKGROUND: Patients often describe fatigue as the most distressing of the symptoms they experienced during their cancer treatment. Fatigue may increase from initial levels experienced during cancer treatment with the addition of radiotherapy (RT). METHODS: Three hundred seventy-two patients completed a Symptom Inventory at the initiation of RT and weekly for 4 weeks thereafter. Descriptive statistics were used to evaluate differences in fatigue at baseline by demographics and diagnosis. Changes over the course of treatment were evaluated by repeated-measures analysis of variance and Student t tests for paired data. The effect of diagnosis, age, gender, and previous treatment on fatigue was investigated by linear and hierarchical regression. RESULTS: Fifty-seven percent of patients reported some degree of fatigue at the initiation of RT. The proportion increased to 76% by Week 3 and then to 78% at Week 5. Eighty-four percent of patients with initial fatigue remained fatigued throughout the 5-week course. Of the 160 patients without initial fatigue, 70% subsequently developed it. By Week 5, only 13% of patients had never reported any fatigue. Severity was found to be related to diagnosis, with patients with prostate carcinoma reporting the least severe fatigue and patients with lung, alimentary, and head and neck carcinoma reporting the most severe fatigue. Neither gender, age, nor total dose of RT predicted significant variance in severity. CONCLUSIONS: Fatigue was a common adverse effect of RT for cancer, reported by more than three-fourths of patients by the third to fifth weeks of treatment. Cancer diagnosis was the only factor found to be significantly related to variation in fatigue severity. Additional studies should be devised to identify other underlying causes of RT-related fatigue.

Management of cancer-related fatigue.

Fatigue is among the most commonly reported symptoms of patients with cancer, with prevalence exceeding 60% in many studies. It is among the most distressing symptoms associated with cancer and cancer treatments because it substantially disturbs patients' quality of life and ability to function optimally on a daily basis. Although the development of this condition has been associated with a number of factors, its etiology remains poorly understood. Important elements to include in any definition of cancer-related fatigue include its pervasiveness, persistence, detrimental effect on quality of life, and its inability to be relieved by rest or sleep. Several validated questionnaires can be used to measure fatigue in patients with cancer, and research efforts are currently focused on ways to distinguish it from depression with which it shares many symptoms. All patients with cancer should be evaluated for fatigue, and treatment options should be considered for those who are experiencing excessive levels of fatigue. Treatment should be individualized according to the underlying pathology when a specific cause has been identified (e.g., anemia, sleep disorder, depression, or metabolic disorder). Nonspecific therapies may be useful in short- and long-term cancer-related fatigue management in many patients. In addition to older therapies, such as hematopoietics, antidepressants, corticosteroids, and psychostimulants, the effectiveness of the new wake-promoting agent modafinil is currently being studied. A more thorough evaluation of the various therapeutic options is required to better define their efficacy and safety profiles in this patient population.

Acustimulation wrist bands are not effective for the control of chemotherapy-induced nausea in women with breast cancer.

This experiment examined the efficacy of an acustimulation wrist band for the relief of chemotherapy-induced nausea using a randomized three-arm clinical trial (active acustimulation, sham acustimulation, and no acustimulation) in 96 women with breast cancer who experienced nausea at their first chemotherapy treatment. Five outcomes related to wrist band efficacy (acute nausea, delayed nausea, vomiting, QOL, and total amount of antiemetic medication used) were examined. The five outcomes were examined separately using analysis of covariance controlling for age and severity of past nausea. There were no significant differences in any of these study measures among the three treatment conditions (P>0.1 for all). Study results do not support the hypothesis that acustimulation bands are efficacious as an adjunct to pharmacological antiemetics for control of chemotherapy-related nausea in female breast cancer patients.

Effect of paroxetine hydrochloride (Paxil) on fatigue and depression in breast cancer patients receiving chemotherapy.

BACKGROUND: Fatigue can significantly interfere with a cancer patient's ability to fulfill daily responsibilities and enjoy life. It commonly co-exists with depression in patients undergoing chemotherapy, suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue. METHODS: We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy randomly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor (SSRI) paroxetine (Paxil, SmithKline Beecham Pharmaceuticals) or an identical-appearing placebo. Patients began their study medication seven days following their first on-study treatment and continued until seven days following their fourth on-study treatment. Seven days after each treatment, participants completed questionnaires measuring fatigue (Multidimensional Assessment of Fatigue, Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist) and depression (Profile of Mood States-Depression subscale [POMS-DD] and Center for Epidemiologic Studies-Depression [CES-D]). RESULTS: Repeated-measures ANOVAs, after controlling for baseline measures, showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D (p = 0.006) and the POMS-DD (p = 0.07) but not in reducing fatigue (all measures, ps > 0.27). CONCLUSIONS: Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo, indicating that a biologically active dose was used, no significant differences between groups on any of the measures of fatigued were observed. Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment.

Patient expectation is a strong predictor of severe nausea after chemotherapy: a University of Rochester Community Clinical Oncology Program study of patients with breast carcinoma.

BACKGROUND: Patients may use their past experiences with nausea, as well as information about the incidence of nausea from chemotherapy that other patients have experienced, to form a prediction, or response expectancy, of nausea from their own upcoming chemotherapy. Mounting evidence suggests that these expectancies relating to nausea are significant predictors, and, likely, contributing factors to the development of treatment-related nausea. METHODS: The patients in the current study were participants in the control arm of a multicenter clinical trial conducted between November 1999 and July 2001 by the University of Rochester Community Clinical Oncology Program. All patients in the current report were age >/= 18 years and were about to begin a first cancer treatment regimen containing doxorubicin. RESULTS: Expectancy of nausea assessed before patients received their first doxorubicin-based chemotherapy treatment was found to be a strong predictor of subsequent nausea and in fact was stronger than previously reported predictive factors, including age, nausea during pregnancy, and susceptibility to motion sickness. Women who believed it was "very likely" that they would have severe nausea from chemotherapy were five times more likely to experience severe nausea than fellow patients who thought its occurrence would be "very unlikely." CONCLUSIONS: Further studies confirming an expectancy of nausea as a risk factor are warranted as are studies examining the benefit to a patient's quality of life from modifying antiemetic treatment guidelines to take into account symptom expectancies. Finally, ethically acceptable interventions that are designed to reduce patients' nausea expectancies or increase their expectancies of nausea control should be developed and studied.

Cancer patients' expectations of experiencing treatment-related side effects: a University of Rochester Cancer Center--Community Clinical Oncology Program study of 938 patients from community practices.

BACKGROUND: Adequate management of treatment-related side effects is important for patients and challenging for clinicians. Side effects generated by various treatments have been characterized reasonably well. However, to the authors' knowledge, less is known regarding what patients expect to experience regarding these side effects and how patient characteristics are related to these expectations. METHODS: Patients with cancer (n = 1015 patients) from 17 Community Clinical Oncology Program (CCOP) institutions affiliated with the University of Rochester Cancer Center CCOP Research Base were surveyed regarding their expectations of experiencing side effects associated with cancer treatment, with 938 patients providing evaluable data. Patients responded to the item, "Indicate your expectations of having this side effect" for 12 common side effects. Patients rated their expectations using a 5-point Likert scale, from 1 ("I definitely will not have this") to 5 ("I definitely will have this"). RESULTS: The median number of symptoms expected (characterized by any value other than one) was nine. The six most expected symptoms were fatigue, nausea, sleep disturbance, weight loss, hair loss, and skin problems. Patients age > 60 years expected to have fewer symptoms than younger patients; female patients expected more side effects than male patients; and patients who had some college education expected more side effects than patients who were high school graduates or had not completed high school. CONCLUSIONS: Patients with cancer clearly exhibit expectations regarding treatment-related side effects; and age, gender, and education level appear to influence these expectations. Further careful characterization of patient expectations and how expectations relate to experience may lead to earlier and more effective management of side effects.

Biobehavioral factors in chemotherapy-induced nausea and vomiting.

Although emesis can be considered a reflex to clear toxins from the body and involves mostly lower brain structures, nausea's purpose appears to be a warning signal to the individual to not engage in behaviors that he or she was doing at the time. As such, it involves the functioning of cognition and memory from higher developed neural structures. Given this, it should not be surprising that biobehavioral factors are important in predicting and controlling nausea. This article reviews the individual characteristics that are clinically useful in predicting which patients will have an increased probability of experiencing nausea or emesis during chemotherapy treatment, and also briefly review psychologic and biobehavioral treatments that can be useful in managing chemotherapy-related nausea.

Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program.

PURPOSE: Fatigue and depression typically occur together in cancer patients, suggesting a common etiology, perhaps based on serotonin. This randomized clinical trial tested whether paroxetine, a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin, would reduce fatigue in cancer patients and whether any reduction was related to depression. PATIENTS AND METHODS: Cancer patients undergoing chemotherapy for the first time were assessed for fatigue. Of 704 patients who reported fatigue at their second chemotherapy cycle, 549 patients were randomly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks. The assessments of fatigue and depression were performed at cycles 3 and 4 of chemotherapy. RESULTS: A total of 244 patients treated with paroxetine and 235 patients treated with placebo provided assessable data. No difference was detected in fatigue between patient groups. At the end of the study, there was a difference between groups in the mean level of depression (Center for Epidemiologic Studies Depression scores, 12.0 v 14.8, respectively; P <.01). CONCLUSION: Paroxetine had no influence on fatigue in patients receiving chemotherapy. A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels.

The efficacy of acupressure and acustimulation wrist bands for the relief of chemotherapy-induced nausea and vomiting. A University of Rochester Cancer Center Community Clinical Oncology Program multicenter study.

As an adjunct to standard antiemetics for the relief of chemotherapy-induced nausea and vomiting (NV), 739 patients were randomly assigned to either: 1) acupressure bands, 2) an acustimulation band, or 3) a no band control condition. Patients in the acupressure condition experienced less nausea on the day of treatment compared to controls (P<0.05). There were no significant differences in delayed nausea or vomiting among the three treatment conditions. Additional analyses revealed pronounced gender differences. Men in the acustimulation condition, but not the acupressure condition, had less NV compared to controls (P<0.05). No significant differences among the three treatment conditions were observed in women, although the reduction in nausea on the day of treatment in the acupressure, compared to the no band condition, closely approached statistical significance (P=0.052). Expected efficacy of the bands was related to outcomes for the acupressure but not the acustimulation conditions.

Nausea and emesis remain significant problems of chemotherapy despite prophylaxis with 5-hydroxytryptamine-3 antiemetics: a University of Rochester James P. Wilmot Cancer Center Community Clinical Oncology Program Study of 360 cancer patients treated in the community.

BACKGROUND: Clinical reports suggest that nausea remains a side effect of chemotherapy despite widespread use of serotonin receptor antagonists. This study summarized the frequency, timing, and intensity of postchemotherapy nausea for patients receiving doxorubicin, cisplatin, or carboplatin. METHODS: Three hundred sixty chemotherapy-naïve patients (73% female) were enrolled in a study testing the ability of an information intervention to reduce nausea. Of these, 322 subjects completed the Morrow Assessment of Nausea and Emesis (MANE), as well as a 5-day self-report diary, at Cycle 1 (300 subjects completed the MANE and self-report diary at Cycle 2). All patients received a 5-hydroxytryptamine-3 receptor antagonist (ondansetron) with dexamethasone on the day of treatment. RESULTS: Seventy-six percent of the patients developed nausea during the 5-day period, beginning with the Cycle 1 infusion, and 73% of patients reported delayed nausea (DN) during Days 2-5. The proportions were similar during Cycle 2. Fifty-five percent of patients described their DN as being of moderate or greater intensity compared with 28% of patients who described acute nausea. Carboplatin was less likely to cause DN than either of the other agents (56% of 106 patients compared with 75% of 47 receiving cisplatin and 83% of 169 taking doxorubicin). The mean peak DN severity was 4.34 (range, 1-7) for doxorubicin, which was significantly higher than the mean peak value for carboplatin (3.66) but was not significantly different from the mean peak value for cisplatin (4.26). Eighteen percent of patients did not experience nausea until Day 3 or later. CONCLUSIONS: Despite prophylaxis with ondansetron, the majority of patients receiving one of these common chemotherapy agents experienced nausea. The frequency of DN was nearly twice that of acute nausea. Results show the need for continued development of antiemetics that are effective against DN.

Reduction in serum cortisol after platinum based chemotherapy for cancer: a role for the HPA axis in treatment-related nausea?

Many adverse effects commonly associated with chemotherapy, such as nausea, vomiting, and fatigue, are also characteristic of adrenal insufficiency. It is conceivable that chemotherapy drugs may directly or indirectly impact the activity of the hypothalamic-pituitary-adrenal axis. We examined this conjecture by characterizing temporal changes in blood cortisol concentrations in women with ovarian carcinoma given chemotherapy. Twenty-three chemotherapy-naïve women with histologically confirmed ovarian cancer underwent serial blood sampling for determination of cortisol levels prior to and every hour for 6 hr following two chemotherapy treatments with cisplatin or carboplatin. Samples were also taken for 4 hr on a comparison day when all study procedures were performed except chemotherapy administration. A significant reduction in serum cortisol was found immediately following infusion of either cisplatin or carboplatin. No progressive reduction in cortisol was found over the two treatment cycles. Because the reduction in cortisol was seen only in the presence of the cytotoxic drug, it is likely that the effect of the drug is "direct" and does not involve overt psychological or circadian mechanisms. The possible role of this reduction in cortisol is discussed in relation to induction of chemotherapy-induced nausea and vomiting.

Fatigue associated with cancer and its treatment.

Fatigue is often related to cancer, and that related to its treatment is the most commonly reported side effect of cancer treatment. It differs from that induced by other causes, such as sleep disturbance and exertion, as the latter are typically alleviated by a period of rest. In contrast to exercise-induced fatigue, the fatigue reported by cancer patients is usually described as an unusual, excessive, whole-body experience that is disproportionate or unrelated to activity or exertion and is not relieved by rest or sleep. Cancer-related fatigue is a subjective experience that has a clear detrimental effect on a cancer patient's quality of life and ability to sustain the usual personal, professional, and social relationships. The fatigue can be pervasive: cancer patients frequently report that fatigue begins with treatment, continues during the course of chemotherapy or radiation treatment, and declines somewhat - but frequently sustains at a higher-than-baseline rate - after treatment is over. It may also persist for several years even in patients with no apparent disease. While a number of researchers have speculated about the nature of cancer-related fatigue, there has been little systematic research on its etiology or treatment. In many aspects our knowledge of the fatigue mechanisms in cancer patients is at a similar stage to that reached in our understanding of anti-cancer therapy-induced nausea and vomiting about 20 years ago. This paper introduces four plausible hypotheses for the development of fatigue. Evidence available to support a role for anemia, adenosine triphosphate, vagal afferents, and the interaction of the HPA/cytokines and 5HT is discussed.