Falls and functional impairments in cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study.

PURPOSE: This study was conducted in order to characterize the prevalence of falls and functional impairments (FIs) and their association with chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors. METHODS: We analyzed baseline assessments from a phase III RCT in cancer survivors with self-reported CIPN scores of >4 out of 10. Patients completed the EORTC QLQ-CIPN-20 for neuropathy and reported falls in the previous 3 months. FIs were defined using the Activities of Daily Living subsection of the Vulnerable Elder's Scale. Associations of baseline characteristics and CIPN with falls and FIs were examined using logistic regression. RESULTS: Of 421 patients, 11.9 % experienced recent falls and 26.6 % reported FIs. Motor neuropathy was the only factor associated with falls (OR = 1.127, p = 0.01). Factors associated with FIs included non-white race (OR = 0.335 white relative to non-white, 0.781, p = 0.01) and greater motor neuropathy scores (OR = 1.262, p < 0.0001). CONCLUSION: CIPN, primarily motor, is associated with falls and FIs. Future prospective research should investigate the ability of motor neuropathy severity to predict falls.

Oral antibiotic prophylaxis of early infection in multiple myeloma: a URCC/ECOG randomized phase III study.

Multiple myeloma (MM) is a malignancy of clonal plasma cells, resulting in an increased production of ineffective immunoglobulins with suppression of non-involved immunoglobulins. Patients with MM are at increased risk of infectious complications, particularly streptococcal and staphylococcal infections. This study evaluated the impact of prophylactic antibiotics on the incidence of serious bacterial infections (SBIs) during the first 2 months of treatment in patients with newly diagnosed MM. Patients with MM receiving initial chemotherapy were randomized on a 1:1:1 basis to daily ciprofloxacin (C; 500 mg twice daily), trimethoprim-sulfamethoxazole (T; DS twice daily) or observation (O) and evaluated for SBI (Eastern Cooperative Oncology Group ≥grade 3) for the first 2 months of treatment. From July 1998 to January 2008, 212 MM patients were randomized to C (n=69), T (n=76) or O (n=67). The incidence of SBI was comparable among groups: C=12.5%, T=6.8% and O=15.9%; P=0.218. Further, any infection during the first 2 months was also comparable (20% vs 23% vs 22%, respectively, P=0.954). We demonstrate that prophylactic antibiotics did not decrease the incidence of SBI (≥grade 3) within the first 2 months of treatment. We conclude that routine use of prophylactic antibiotics should not be mandated for patients receiving induction chemotherapy.

The efficacy of calcitriol therapy in the management of bone loss and fractures: a qualitative review.

UNLABELLED: Osteoporosis, a skeletal disorder characterized by a reduction in bone strength, increases fracture risk. Primary osteoporosis is usually a result of reduced bone mineral density as a consequence of natural aging. Secondary osteoporosis is usually a result of a disease, such as cystic fibrosis, or medical treatment, such as corticosteroids or cancer treatment. INTRODUCTION: Currently, ten million Americans are osteoporotic and an additional 34 million have the precursor condition, osteopenia. Osteoporosis leads to 1.5 million fractures and 500,000 hospitalizations annually. Osteoporosis-related fractures increase mortality and reduce quality of life. Calcitriol, the active form of vitamin D, regulates intestinal calcium absorption, among other actions. During the past four decades, many clinical trials investigating the effect of calcitriol on bone loss have been performed. METHODS: We conducted a systematic qualitative review of clinical trials that assessed calcitriol for the treatment of osteoporosis and bone loss. In these clinical trials, calcitriol was used as a monotherapy and in combination with other therapeutic bone agents. RESULTS AND CONCLUSION: Studies using calcitriol monotherapy, although not conclusive, found that calcitriol slowed the rate of bone loss in a variety of populations. Calcitriol in combination with other therapeutic bone agents was shown to have additional bone-preserving effects when compared to the use of therapeutic bone agents alone. A common side-effect of calcitriol therapy was hypercalcemia and hypercalciuria, but the degree of hypercalcemia was mild. Recent research found that intermittent dosing can reduce hypercalcemia rates. Calcitriol, alone or in combination with other agents, should be considered for the therapy of osteoporosis.

Associations between adult and childhood secondhand smoke exposures and fecundity and fetal loss among women who visited a cancer hospital.

BACKGROUND: A large percentage of the population continues to be exposed to secondhand smoke (SHS). Although studies have consistently linked active smoking to various pregnancy outcomes, results from the few studies examining SHS exposure and pregnancy difficulties have been inconsistent. METHODS: Approximately 4800 women who presented to Roswell Park Cancer Institute between 1982 and 1998 and reported being pregnant at least once were queried about their childhood and adult exposures to SHS using a standardised questionnaire. Women were asked to report on selected prenatal pregnancy outcomes (fetal loss and difficulty becoming pregnant). RESULTS: Approximately 11.3% of women reported difficulty becoming pregnant, while 32% reported a fetal loss or 12.4% reported multiple fetal losses. 40% reported any prenatal pregnancy difficulty (fetal loss and/or difficulty becoming pregnant). SHS exposures from their parents were associated with difficulty becoming pregnant (OR = 1.27, 95% CI 1.03 to 1.56) and lasting >1 year (OR = 1.34, 95% CI 1.12 to 1.60). Exposure to SHS in both at home during childhood and at the time of survey completion was also associated with fetal loss (OR = 1.39, 95% CI 1.17 to 1.66) and multiple fetal losses (OR = 1.62, 95% CI 1.25 to 2.11). Increasing current daily hours of SHS exposure as an adult was related to the occurrence of both multiple fetal loss and reduced fecundity (p(trend) < 0.05). CONCLUSIONS: Reports of exposures to SHS during childhood and as an adult were associated with increased odds for prenatal pregnancy difficulties. These findings underscore the public health perspective that all people, especially women in their reproductive years, should be fully protected from tobacco smoke.

Post-treatment skin reactions reported by cancer patients differ by race, not by treatment or expectations.

Cancer patients may experience skin problems while undergoing chemotherapy and radiation therapy. Frequency of skin reactions may be influenced by skin pigmentation and psychological factors. A Symptom Inventory completed by 656 cancer patients nationwide before and after chemotherapy, radiation therapy, or chemotherapy plus radiation therapy was analysed to determine if treatment type, race (Black vs White), and pretreatment expectations influenced post-treatment skin reactions. Subsequent analysis of a local Symptom Inventory completed weekly for 5 weeks by 308 patients receiving radiation therapy examined severity of reported skin reactions. Significantly more patients receiving radiation therapy had stronger expectations of skin problems (62%) than patients receiving chemotherapy (40%, P=0.001) or chemotherapy plus radiation therapy (45%, P=0.003). Overall, expectations did not correlate with patient reported post-treatment skin problems in white (r=0.014, P=0.781) or black (r=0.021, P=0.936) patients. Although no significant difference was found between black and white patients in their pretreatment expectations of skin problems (P=0.32), black patients (10 out of 18, 56%) reported more skin problems than white patients (90 out of 393, 23%, P=0.001). Similarly, the local study showed that significantly more black patients (1 out of 5, 20%) reported severe skin reactions at the treatment site than white patients (12 out of 161, 8%). A direct correlation was observed between severity of skin problems and pain at the treatment site (r=0.541, P<0.001). Total radiation exposure did not significantly correlate with the report of skin problems at the treatment site for white or black patients. Overall, black patients reported more severe post-treatment skin problems than white patients. Our results suggest that symptom management for post-treatment skin reactions in cancer patients receiving radiation treatment could differ depending on their racial background.

The role of patients' expectations in the development of anticipatory nausea related to chemotherapy for cancer.

Although anticipatory nausea (AN), which is reported by one-third of patients receiving chemotherapy for cancer, is thought to develop primarily by classical conditioning, response expectancies may also be important. The role of patients' expectations of nausea in the development of AN was examined in 63 female cancer patients receiving their first course of chemotherapy. Twenty women (32%) expected to experience nausea and twelve (19%) reported AN before the third cycle. Pretreatment expectations predicted AN at cycle three (Spearman's r = 0.41, P = 0.001). AN developed in 40% of patients who expected nausea, 13% of those who were uncertain whether they would develop it, and no patients who did not expect nausea. Logistic regression indicated that expecting nausea was the strongest predictor (chi(2) =13.15; P < 0.001). Results support a role for cognitive factors in the development of chemotherapy side effects and suggest testing psychologic interventions to modify patients' expectations.

Relationship of gastric myoelectrical and cardiac parasympathetic activity to chemotherapy-induced nausea.

OBJECTIVES: We evaluated (a) whether pretreatment levels of gastric tachyarrhythmia, a dysrhythmic pattern of gastric myoelectrical activity, or cardiac parasympathetic activity are associated with the development of chemotherapy-induced nausea and (b) whether chemotherapy-induced nausea is preceded by an increase in gastric tachyarrhythmia and a decrease in cardiac parasympathetic activity, as has been observed during motion sickness. METHODS: Electrogastrograms and estimates of respiratory sinus arrhythmia (RSA) were obtained from cancer chemotherapy patients before treatment and for approximately 24 hours after treatment. RESULTS: Higher levels of pretreatment gastric tachyarrhythmia were observed on chemotherapy sessions that were followed by posttreatment reports of nausea. Pretreatment levels of RSA, however, did not differ between chemotherapy treatments that were and were not followed by nausea. No statistically significant changes in gastric tachyarrhythmia or RSA were observed prior to first reports of nausea following chemotherapy. CONCLUSIONS: In contrast to motion sickness, chemotherapy-induced nausea may not be related to an increase in dysrhythmic gastric myoelectrical activity; however, higher levels of pretreatment gastric tachyarrhythmia may be related to posttreatment reports of chemotherapy-induced nausea.

Nausea and vomiting remain a significant clinical problem: trends over time in controlling chemotherapy-induced nausea and vomiting in 1413 patients treated in community clinical practices.

Data from 1413 outpatients in community-based clinical practices were collected in order to characterize the use and effectiveness of 5-HT(3) receptor antagonists for control of chemotherapy-induced nausea and vomiting (NV). Patients were divided by treatment starting date into six cohorts for trend analysis. In addition, NV symptoms were compared in 252 patients treated prior to the commercial introduction of the 5-HT(3) receptor antagonist antiemetics, and an equal number of patients treated after their introduction. A comparison of cohorts revealed a significant (P = 0. 027) downward trend over time for the frequency of post-treatment vomiting episodes, but not for frequency of post-treatment nausea (P = 0.69). The average duration of nausea following treatment increased significantly over time (P = 0.003). Although the introduction of 5-HT(3) receptor antagonist antiemetics has apparently led to a significant reduction in the frequency of post-treatment vomiting, there has been an accompanying increase in the duration of post-treatment nausea.

Patient expectations as predictor of chemotherapy-induced nausea.

We examined the relationship between patients' pretreatment expectations for nausea and vomiting and their subsequent development in a homogeneous group of 29 female cancer patients receiving platinum-containing chemotherapy as inpatients (Study 1) and in 81 subjects with any of a variety of cancer diagnoses treated largely as outpatients (Study 2). Each study found a significant relationship between patients' expectations for nausea development measured prior to their first treatment and their mean postchemotherapy nausea severity (both, p < 0.05). Patients' expectations accounted for unique variance in nausea severity in each study even after controlling for known pharmacological and physiological predictors of nausea (Study 1: delta R2 = .18, p < .04; Study 2: delta R2 = .05, p < .03). By contrast, we found no significant relationships between expectations for vomiting and subsequent vomiting. Our results support the view that patients' expectations for nausea affect its subsequent development, indicating the presence of a significant psychological component in treatment-related nausea. Implications of this are discussed.

Vagal changes following cancer chemotherapy: implications for the development of nausea.

Many physiological changes that occur contemporaneously with nausea are mediated by the autonomic nervous system, but the specific autonomic changes associated with nausea have not been characterized. Cardiac parasympathetic (vagal) activity as indicated by heart rate variability, measured as the standard deviation of successive differences (SDSD) in beat-to-beat intervals, was assessed in 24 women with ovarian cancer immediately prior to and accompanying nausea that occurred following anticancer chemotherapy. A progressive increase in SDSD followed infusion of the chemotherapy agent, indicating a rise in cardiac parasympathetic (vagal) activity, with onset of nausea consistently occurring after the peak activity had been reached, at a time when SDSD was decreasing. An increase in parasympathetic activity seems to set the stage for the expression of nausea but an additional stimulus is apparently needed to finally trigger the event.

Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.

BACKGROUND: Hot flashes are the most frequently reported side effect of tamoxifen treatment. Although hormones are an effective treatment, their safety is questionable in women with breast cancer. It is therefore important to evaluate nonhormonal treatments for hot flashes. OBJECTIVE: To evaluate the effectiveness of oral clonidine for control of hot flashes associated with tamoxifen therapy in postmenopausal women with breast cancer. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: University of Rochester Cancer Center Community Clinical Oncology Program. PATIENTS: 194 postmenopausal women with breast cancer who were receiving adjuvant tamoxifen therapy. INTERVENTION: Oral clonidine hydrochloride, 0.1 mg/d, or placebo for 8 weeks. MEASUREMENTS: In a daily diary, patients recorded number, duration, and severity of hot flashes and overall quality-of-life score (on a 10-point scale) during a 1-week baseline period and during the 4th, 8th, and 12th weeks of the study. RESULTS: Patients in the placebo and treatment groups were similar in age, duration of tamoxifen use, reported frequency and duration of hot flashes at baseline, and dropout rates. One hundred forty-nine patients completed 12 weeks of follow-up. The mean decrease in hot flash frequency was greater in the clonidine group than in the placebo group after 4 weeks of treatment (37% compared with 20% [95% CI for difference, 7% to 27%]) and 8 weeks of treatment (38% compared with 24% [CI for difference, 3% to 27%]). Patients receiving clonidine were more likely than patients receiving placebo to report difficulty sleeping (41% compared with 21%; P = 0.02). A significant difference was seen in the mean change in quality-of-life scores (0.3 points in the clonidine group compared with -0.2 points in the placebo group; P = 0.02) at 8 weeks, although the median difference was 0 in both groups. CONCLUSION: Oral clonidine, 0.1 mg/d, is effective against tamoxifen-induced hot flashes in postmenopausal women with breast cancer.

Sources of information used by patients to learn about chemotherapy side effects.

BACKGROUND: Little is known about the relative importance of specific information sources patients use to obtain knowledge about treatment side effects. The authors examined information sources used to learn about side effects, why patients believe they will experience some but not others, and the meanings side effects have in terms of treatment efficacy. METHODS: Before treatment, 31 ovarian cancer patients and 81 men and women with a variety of cancer diagnoses completed a questionnaire assessing their expectations about experiencing specific side effects of chemotherapy and information sources used. RESULTS: The doctor or nurse was the most frequently cited source of side-effect information, with readings second. While most thought they would get certain side effects because the doctor or nurse had said so, most instinctively believed they would not get others. CONCLUSIONS: Patients relied on medical and non-medical information sources. Further research could examine other sources for their influences on information-seeking activities.

Changes in clinical measures of autonomic nervous system function related to cancer chemotherapy-induced nausea.

Individual cancer patients differ in their nausea/vomiting response to chemotherapy. It is not known why patients receiving the same chemotherapy have different severity of side effects. Several lines of research implicate the autonomic nervous system (ANS) in the development of chemotherapy-induced nausea. We examined the association between autonomic reactivity and the level of nausea experienced following chemotherapy in 20 patients with ovarian cancer treated with cisplatin or carboplatin who received the same antiemetic. We applied eight common non-invasive clinical tests of autonomic function prior to inpatient chemotherapy treatment, 2 h after treatment and again 24 h following treatment. Two hours after chemotherapy and before any nausea was reported by the patients, the nine patients who subsequently experienced high levels of nausea had a greater overall percentage of abnormal clinical ANS tests than the 11 patients who subsequently developed low levels of nausea (P < 0.01). Twenty-four hours after treatment, the overall number of abnormal autonomic tests remained non-significantly higher than at the pretreatment baseline for the high nausea group. Demographic and clinical characteristics were not related to chemotherapy-induced nausea in this sample. Autonomic reactivity appears to be related to the development of nausea following chemotherapy. Further investigation of ANS involvement in chemotherapy-induced nausea could increase understanding of nausea etiology and potentially lead to the prediction of susceptible patients.

Group psychotherapy for recently diagnosed breast cancer patients: a multicenter feasibility study.

As many as 80% of breast cancer patients report significant distress during initial treatment, yet there is little in the way of systematic psychotherapeutic interventions for women coping with the stress of a recent diagnosis of breast cancer. The literature on psychotherapeutic treatment of cancer patients provides uniform evidence for an improvement in mood, coping and adjustment as a result of group therapy. The present study examined the feasibility of implementing a manualized treatment, supportive-expressive group psychotherapy, in busy oncology practices across the US. This intervention was applied to women with primary breast cancer in a manner which tests not only the efficacy of the approach but also its accessibility to group therapists not previously experienced in its use. One hundred and eleven breast cancer patients within 1 year of diagnosis were recruited from ten geographically diverse sites of the National Cancer Institute's Community Clinical Oncology Program (CCOP) and two academic medical centers. Two therapists from each site were trained in supportive-expressive group psychotherapy. Training consisted of participation in a workshop, reading a treatment manual, and viewing explanatory videotapes. Each patient participated in a supportive-expressive group that met for 12 weekly sessions lasting 90 min. Assessment of mood disturbance was made at entry, 3, 6, and 12 months. Results indicated a significant 40% decrease in the Total Mood Disturbance (TMD) scores of the Profile of Mood States (POMS) (ANOVA F [2,174]=3.98, p<0.05). The total symptom score of the Hospital Anxiety and Depression Scale (HADS) was likewise significantly reduced over the 6-month period (F [2, 174]=5.2, p<0.01). Similarly, the total score of the Impact of Event Scale (IES) was significantly reduced (F [2,174]=4.0, p<0.05). There was substantial uniformity of treatment effect across sites. Outcome was independent of stage of disease (I vs. II). We conclude that this treatment program can be effectively implemented in a community setting and results in reduced distress among breast cancer patients.

Use of 5-HT3 receptor antagonists to prevent nausea and emesis caused by chemotherapy for patients with breast carcinoma in community practice settings.

BACKGROUND: Although 5-HT3 receptor antagonists are clinically more effective in controlling emesis, particularly that caused by high dose cisplatin, than previously available agents, they appear to be less effective against nausea. This report focuses on the effectiveness of these agents against nausea and emesis in patients receiving two moderately emetogenic combination chemotherapy regimens as treatment for breast carcinoma in community practice settings. METHODS: Six hundred ninety-two breast carcinoma patients (688 female, 4 male; mean age, 51 years) enrolled in a nonrandomized study completed the Morrow Assessment of Nausea and Emesis (MANE) following 4 consecutive chemotherapy treatments. The frequency, duration, and severity of postchemotherapy nausea (PN) and postchemotherapy emesis (PE) were compared by type of antiemetic (5-HT3 receptor antagonist vs. other) and chemotherapy regimen (cyclophosphamide and doxorubicin with or without 5-fluorouracil [CA/CAF] vs. cyclophosphamide, methrotrexate, and 5-fluorouracil [CMF]). RESULTS: Within each regimen, the mean duration of PN was significantly longer for patients who received a 5-HT3 receptor antagonist than for those who were not given an antiemetic of that type (CA: 40.3 hours vs. 29.6 hours, P < 0.05; CMF: 37.6 hours vs. 30.2 hours, P < 0.05). There were no significant differences in the frequency or severity of nausea or in the frequency, severity, or duration of emesis by type of antiemetic for patients receiving either regimen. CONCLUSIONS: The results of this observational study suggest that 5-HT3 receptor antagonists are no more effective than other commonly used medications in controlling postchemotherapy nausea and emesis in women with breast carcinoma who are treated with moderately emetogenic chemotherapy in community practice settings. In fact, they may be associated with significant prolongation of the course of postchemotherapy nausea.

Anticipatory nausea and vomiting in the era of 5-HT3 antiemetics.

Cancer chemotherapy is known to lead to nausea and vomiting in a large proportion of cases. If emesis is severe it can lead in its turn to anticipatory nausea and vomiting (ANV), which cannot be controlled by antiemetic medication. The etiology of ANV and various methods that have been used to counteract the condition are discussed.

Statistical considerations in the design, conduct and analyses of antiemetic clinical trials. An emerging consensus.

Various aspects of trial design and planning for clinical testing of antiemetic therapies administered to cancer patients are considered. It is generally felt that a randomized double-blind parallel-arm design is the best. Ways of achieving adequate power of such studies are discussed briefly, as is the need for previous identification of primary and secondary end-points. Finally, summary recommendations are given.

Initial control of chemotherapy-induced nausea and vomiting in patient quality of life.

The side effects commonly experienced by patients receiving chemotherapy for the treatment of cancer can challenge many aspects of daily life. Nausea and vomiting, the most common side effects reported by patients, affect the ability to continue with usual life activities and, thus have a pronounced impact on quality of life. This paper reviews studies of the impact of nausea and emesis on quality of life, and highlights the importance of prevention of these side effects by presenting new data on how persistent uncontrolled nausea and vomiting can be. The Morrow Assessment of Nausea and Emesis (MANE) was used to collect information on symptoms experienced by consecutive patients starting chemotherapy between September 1987 and December 1995 at any of 18 geographically diverse member sites of the University of Rochester Cancer Center Community Clinical Oncology Program. Data from 1,413 patients were collected after each of four successive chemotherapy treatments. Reported incidences of posttreatment nausea and posttreatment vomiting after the first treatment were 59.4% and 28.6%, respectively. Occurrence of nausea/vomiting at the first treatment was a strong predictor of nausea/vomiting at later treatments. Of the 839 patients reporting initial nausea, 763 (90.9%) reported nausea at at least one subsequent treatment, and approximately 59% reported nausea after all three subsequent treatments. Fewer than half (45.6%) of the patients who had no nausea at the first treatment developed it later. The majority (72.0%) of patients reporting vomiting at the first treatment also reported subsequent vomiting, 30.7% of whom experienced emesis at all remaining treatments. Conversely, 76.2% of patients who were emesis-free at the first treatment remained so for all later treatments. These findings show a continuing need for further progress in controlling nausea and vomiting, and demonstrate the importance of aggressive nausea/vomiting control at the first treatment. In addition, more emphasis on controlling chemotherapy-induced nausea after its initial occurrence is necessary.

Progress in reducing anticipatory nausea and vomiting: a study of community practice.

Chemotherapy-related nausea and vomiting (NV) in 300 consecutive patients treated in community practices prior to the availability of 5-HT3 antiemetics (9/87 to 1/91) were compared with NV in a second sample of 300 patients treated after their commercial introduction (9/93 to 2/95). Eighty-six percent of the later patients received 5-HT3 antiemetics, and significantly fewer (43.3%) reported one or more episodes of posttreatment vomiting during their first four cycles of chemotherapy compared with those in the previous sample (55.0%: P < .01). Identical numbers of both groups (79.3%) reported at least one episode of posttreatment nausea. A significant increase in the average duration of both posttreatment nausea (from 28.1 h to 37.2 h; P = 0.001) and posttreatment vomiting (from 10.9 h-16.5 h, P = .02) was found; no significant differences were seen in the reported severity of either symptom. The proportion of patients experiencing at least one episode of anticipatory nausea (31.0% vs 32.0%) or anticipatory vomiting (7.7% vs 6.3%) did not differ significantly (P > 0.5) between groups, nor were there significant differences in the duration or severity of anticipatory symptoms (P > 0.4 for all comparisons). The reduction in the frequency of posttreatment vomiting supports research findings of efficacy. Findings of an increase in duration of posttreatment nausea and emesis and no change in the frequency of posttreatment nausea or in anticipatory symptoms show a continuing need for progress in control of posttreatment emesis and emphasize the need for further research on the control of chemotherapy-induced nausea.