Pralatrexate in Combination with Oxaliplatin in Advanced Esophagogastric Cancer: A Phase II Trial with Predictive Molecular Correlates.

The purpose of our study was to evaluate the efficacy of a combination of pralatrexate plus oxaliplatin in advanced esophagogastric cancer (EGC), analyze the impact of polymorphisms in folate metabolism pathway genes on toxicity and efficacy of pralatrexate, and to evaluate microRNA profile of tumor epithelium as a predictive biomarker. This was a two-stage trial with a safety lead in cohort and a primary endpoint of overall response rate (ORR). Patients received biweekly intravenous oxaliplatin (85 mg/m2) and pralatrexate (Dose level 1 [D1], 120 mg/m2; dose level-1 [D-1] 100 mg/m2). Single-nucleotide polymorphisms (SNP) in genes encoding proteins involved in pralatrexate metabolism were evaluated in germline DNA. microRNA profiling of the tumor epithelium was performed. ORR was 26%. Dose-limiting toxicities were observed in 2 of 4 patients at D1 and none at D-1. The T>C polymorphism in DHFR rs11951910 was significantly associated with lower progression-free survival (PFS; P ≤ 0.01), whereas the presence of the SLC19A1 rs2838957 G>A polymorphism was associated with improved PFS (P = 0.02). Presence of the GGH rs3780130 A>T and SLC19A1 rs1051266 G>A polymorphisms were significantly associated with better overall survival (OS; P = 0.01), whereas GGH rs7010484 T>C polymorphism was associated significantly with reduced OS (P = 0.04). There was no correlation between epithelial microRNA expression profile with disease progression or response. We conclude that the combination of oxaliplatin and pralatrexate is safe, is well tolerated, and has modest efficacy in advanced EGC. Pharmacogenomic analysis may be relevant to the use of pralatrexate in combination with platinum agents.

Positive effects of acupressure bands combined with relaxation music/instructions on patients most at risk for chemotherapy-induced nausea.

PURPOSE: Research by our group has shown that acupressure bands are efficacious in reducing chemotherapy-induced nausea (CIN) for breast cancer patients who expect nausea, and that their effectiveness in controlling CIN can largely be accounted for by patients' expectations of efficacy, i.e., a placebo effect. The present research examined if the effectiveness of acupressure bands could be enhanced by boosting patients' expectation of the bands' efficacy. METHODS: Two hundred forty-two chemotherapy-naïve patients with breast cancer who expected nausea were randomized. Arms 1 and 2 received acupressure bands, plus a relaxation MP3 and written handout that were either expectancy-enhancing (arm 1) or expectancy-neutral (arm 2). Arm 3 was the control without bands or MP3 and received standard care. All participants received guideline-specified antiemetics. RESULTS: Peak CIN for arms 1, 2, and 3 on a 1-7 scale was 3.52, 3.55, and 3.87, respectively (p = 0.46). Because no differences were observed between arms 1 and 2 (primary analysis), we combined these two arms (intervention) and compared them to controls for the following analyses. A significant interaction was found between intervention/control and receiving doxorubicin-based chemotherapy (yes/no) and pre-treatment anxiety (high/low). Intervention patients receiving doxorubicin had lower peak CIN than controls (3.62 vs. 4.38; p = 0.02). Similarly, intervention patients with high pre-treatment anxiety had a lower peak CIN than controls (3.62 vs. 4.62; p = 0.01). CONCLUSIONS: In breast cancer patients undergoing chemotherapy and having high CIN expectation, acupressure bands combined with a relaxation recording were effective in reducing CIN for patients who received doxorubicin or had high anxiety.

Racial Differences in Information Needs During and After Cancer Treatment: a Nationwide, Longitudinal Survey by the University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program.

Before treatment, cancer patients need information about side effects and prognosis, while after treatment they need information to transition to survivorship. Research documenting these needs is limited, especially among racial and ethnic minorities. This study evaluated cancer patients' needs according to race both before and after treatment. We compared white (n = 904) to black (n = 52) patients receiving treatment at 17 National Cancer Institute Community Oncology Research Program (NCORP) sites on their cancer-related concerns and need for information before and after cancer treatment. Two-sample t test and chi-squared analyses were used to assess group differences. Compared to white patients, black patients reported significantly higher concerns about diet (44.3 vs. 25.4 %,) and exercise (40.4 vs. 19.7 %,) during the course of treatment. Compared to whites, blacks also had significantly higher concern about treatment-related issues (white vs. black mean, 25.52 vs. 31.78), self-image issues (7.03 vs. 8.60), family-related issues (10.44 vs. 12.84), and financial concerns (6.42 vs. 8.90, all p < 0.05). Blacks, compared to whites, also had significantly greater post-treatment information needs regarding follow-up tests (8.17 vs. 9.44), stress management (4.12 vs. 4.89), and handling stigma after cancer treatment (4.21 vs. 4.89) [all p < 0.05]. Pre-treatment concerns and post-treatment information needs differed by race, with black patients reporting greater information needs and concerns. In clinical practice, tailored approaches may work particularly well in addressing the needs and concerns of black patients.

Buspirone for management of dyspnea in cancer patients receiving chemotherapy: a randomized placebo-controlled URCC CCOP study.

PURPOSE: Cancer-related dyspnea is a common, distressing, and difficult-to-manage symptom in cancer patients, resulting in diminished quality of life and poor prognosis. Buspirone, a non-benzodiazepine anxiolytic which does not suppress respiration and has proven efficacy in the treatment of generalized anxiety disorder, has been suggested to relieve the sensation of dyspnea in patients with COPD. The main objective of our study was to evaluate whether buspirone alleviates dyspnea in cancer patients. METHODS: We report on a randomized, placebo-controlled trial of 432 patients (mean age 64, female 51%, lung cancer 62%) from 16 participating Community Clinical Oncology Program (CCOP) sites with grade 2 or higher dyspnea, as assessed by the Modified Medical Research Council Dyspnea Scale. Dyspnea was assessed by the Oxygen Cost Diagram (OCD; higher scores are better) and anxiety by the state subscale of the State-Trait Anxiety Inventory (STAI-S; lower scores are better) at baseline and after the 4-week intervention (post-intervention). RESULTS: Mean scores from baseline to post-intervention for buspirone were OCD 8.7 to 9.0 and STAI-S 40.5 to 40.1 and for placebo were OCD 8.4 to 9.3 and STAI-S 40.9 to 38.6 with raw improvements over time on both measures being greater in the placebo group. Analysis of covariance (ANCOVA) controlling for baseline scores showed no statistically significant difference between groups for OCD (P = 0.052) or STAI-S (P = 0.062). CONCLUSION: Buspirone did not result in significant improvement in dyspnea or anxiety in cancer patients. Thus, buspirone should not be recommended as a pharmacological option for dyspnea in cancer patients.

Hot flashes severity, complementary and alternative medicine use, and self-rated health in women with breast cancer.

CONTEXT: Hot flashes (HF) are a common distressing symptom in women with breast cancer (BC). Current pharmacologic options are moderately effective and are associated with bothersome side effects. Complementary and alternative medicine is commonly used by cancer patients. However, information on the association of hot flashes severity with such use and self-rated health is lacking. OBJECTIVE: To examine the hot flashes severity in women with breast cancer and its association with complementary and alternative medicine use and self-rated health (SRH). DESIGN: Longitudinal multicenter study to assess information needs of cancer outpatients. PARTICIPANTS: Patients with a diagnosis of breast cancer who were scheduled to undergo chemotherapy and/or radiotherapy. OUTCOME MEASURES: Hot flashes severity (0 = not present and 10 = as bad as you can imagine), use of complementary and alternative medicine (yes/no), and self-rating of health (SRH) status post-treatment and six-months thereafter (1-5, higher score = better SRH). RESULTS: The majority of women with HF (mean age = 54.4 years) were Caucasian and married, with higher education, and 93% had received surgical treatment for BC. At the end of treatment, 79% women reported experiencing HF [mean severity = 5.87, standard deviation (SD) = 2.9]; significantly more severe HF were reported by younger women with poor SRH, poor performance status, and those reporting doing spiritual practices. At follow-up, 73% had HF (mean severity = 4.86, SD = 3.0), and more severe HF were reported by younger women with poor self-rated health who had undergone chemotherapy plus radiotherapy, used vitamins, and did not exercise. CONCLUSIONS: A high percentage of women experienced hot flashes at the end of treatment and at six-month follow-up. A significant association of hot flashes severity with spiritual practice, increased vitamin use, and reduced exercise emphasize the need for future studies to confirm the results. This can facilitate safe use of complementary and alternative medicine and favorable outcomes while managing cancer-related hot flashes.

Phase II study of perioperative chemotherapy with cisplatin and pemetrexed in non-small-cell lung cancer.

INTRODUCTION: Pathologic complete response (pCR) with neoadjuvant chemotherapy is associated with improved survival in many solid tumors. We evaluated pCR rate of cisplatin with pemetrexed in non-small-cell lung cancer. METHODS: Patients with stages IB to IIIA non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 1 were enrolled in this single-arm phase II trial using two-stage design with 90% power to detect pCR rate of more than or equal to 10%. Pretreatment mediastinal lymph node biopsy was required. Patients received three cycles of cisplatin 75 mg/m with pemetrexed 500 mg/m (day 1 every 21 days) preoperatively and additional two cycles within 60 to 80 days after surgery. The primary end point was pCR. Polymorphisms in FPGS, GGH, SLC19A1, and TYMS genes were correlated with treatment outcomes. RESULTS: Thirty-eight patients were enrolled, with median age of 62.5 years. Preoperatively, 26% had squamous histology, and 34% had biopsy-proven N2 involvement. R0 resection was achieved in 94% of the 34 patients who underwent surgery, and 54% had documented N2 clearance. There was no pCR seen. Median disease-free survival (DFS) and overall survival of these patients have not yet been reached in contrast to median of 13.8 and 24.2 months, respectively, in patients with persistent N2 disease (p = 0.3241 and p = 0.1022, respectively). There was a statistically significant association between DFS and postoperative tumor, node, metastasis stage (p = 0.0429), SLC19A1 rs3788189 TT genotype (p = 0.0821), and viable tumor defined as less than or equal to 10% of resected specimen (p = 0.026). CONCLUSION: The primary end point was not met. Patients with N2 clearance, less than or equal to 10% viable tumor in the resected specimen, and SLC19A1 rs3788189 TT genotype have favorable DFS outcomes.

An exploratory study on the effects of an expectancy manipulation on chemotherapy-related nausea.

CONTEXT: Previous research has shown that the effectiveness of acupressure bands in reducing chemotherapy-related nausea is related to patients' expectations of efficacy. OBJECTIVE: To test whether an informational manipulation designed to increase expectation of efficacy regarding acupressure bands would enhance their effectiveness. METHODS: We conducted an exploratory, four-arm, randomized clinical trial in breast cancer patients about to begin chemotherapy. All patients received acupressure bands and a relaxation CD. This report focuses on Arm 1(expectancy-neutral informational handout and CD) compared with Arm 4 (expectancy-enhancing handout and CD). Randomization was stratified according to the patient's level of certainty that she would have treatment-induced nausea (two levels: high and low). Experience of nausea and use of antiemetics were assessed with a five-day diary. RESULTS: Our expectancy-enhancing manipulation resulted in improved control of nausea in the 26 patients with high nausea expectancies but lessened control of nausea in 27 patients having low nausea expectancies. This interaction effect (between expected nausea and intervention effectiveness) approached statistical significance for our analysis of average nausea (P=0.084) and reached statistical significance for our analysis of peak nausea (P=0.030). Patients receiving the expectancy-enhancing manipulation took fewer antiemetic pills outside the clinic (mean(enhanced)=12.6; mean(neutral)=18.5, P=0.003). CONCLUSION: This exploratory intervention reduced antiemetic use overall and also reduced nausea in patients who had high levels of expected nausea. Interestingly, it increased nausea in patients who had low expectancies for nausea. Confirmatory research is warranted.

Acupressure bands are effective in reducing radiation therapy-related nausea.

Previous studies have shown that acupressure bands can reduce chemotherapy-related nausea. Patients' expectations of efficacy account for part of this outcome. We conducted a three-arm randomized clinical trial to investigate the effectiveness of acupressure bands in controlling radiation therapy-induced nausea and to test whether an informational manipulation designed to increase expectation of efficacy would enhance the effectiveness of the acupressure bands. Patients who experienced nausea at prior treatments were randomized to either standard care (Arm 1, n=29) or standard care plus acupressure bands with either neutral (Arm 2, n=30) or positive (Arm 3, n=29) information regarding the efficacy of the bands. Patients reported nausea for two days prior to randomization (baseline) and for five days following using a seven-point semantic rating scale (1=not nauseated to 7=extremely nauseated). Patients in Arms 2 and 3 combined reported greater reduction in average nausea than patients in Arm 1 (P=0.01; mean(bands)=0.70, mean(no bands)=0.10). This equates to a 23.8% decrease in nausea in the band groups compared to a 4.8% decrease in the control group, a 19% difference. The informational manipulation failed to alter efficacy expectations and there was no statistically significant difference in nausea between patients in Arms 2 and 3. Acupressure bands are an effective, low-cost, nonintrusive, well-accepted, and safe adjunct to standard antiemetic medication. An attempt to boost the efficacy of the acupressure bands by providing positive information was not successful.

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.

Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): implications for studies testing initial treatment of brain tumors.

PURPOSE: To determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma. METHODS AND MATERIALS: Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of > or =60, and adequate pulmonary function were eligible. All patients provided informed consent. Standard RT started within 5 weeks of diagnosis. In both arms, 150 mg/m(2) of TMZ was given on Days 1-5 of RT. In Arm 1, 200 mg/m(2) of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m(2) of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles. RESULTS: A total of 15 and 14 patients were enrolled in the two pilot arms. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose. CONCLUSION: The results of these pilot studies have implications for the design of studies testing the initial treatment of brain tumors. Because of the poor tolerance of the combination, the multicooperative group Phase III study consists of two randomized arms of single-agent carmustine vs. single-agent TMZ.

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.

Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma.

BACKGROUND: Although temozolomide is active against recurrent malignant glioma, responses in many patients are modest and short-lived. Temozolomide may prove more effective in combination with other agents. Therefore, combination oral chemotherapy for these patients is a particularly attractive approach. METHODS: The authors conducted a Phase I study of temozolomide in combination with escalating doses of oral etoposide (VP-16) to determine the maximum tolerated doses of these two agents when given together. The temozolomide dose was fixed at 150 mg/m(2) per day on Days 1-5. The oral VP-16 was escalated in cohorts of 3 to 6 patients by numbers of days of VP-16 administered: 50 mg/m(2) per day, Days 1-5 (dose level 1), Days 1-8 (dose level 2), Days 1-12 (dose level 3), Days 1-16 (dose level 4), and Days 1-20 (dose level 5). Therapy was given in 28-day cycles. RESULTS: Of the 29 patients enrolled, 26 were fully evaluable and 3 were partially evaluable for toxicity. The 29 patients received a total of 92 cycles. The median age of the patients was 49 years (range, 28-76 years). Diagnoses included glioblastoma (n = 19), gliosarcoma (n = 3), anaplastic astrocytoma (n = 5), and anaplastic oligoastrocytoma (n = 2). The median time from diagnosis to disease recurrence was 8 months (3-188 months). Twenty patients were treated at the first disease recurrence, seven at the second, and two at the third. Twenty-four patients (83%) were receiving anticonvulsants and 24 were receiving dexamethasone. All patients had received previous radiation, and 25 of 29 had been treated with chemotherapy previously. Of the 3 patients at dose level 1, none had dose-limiting toxicity (DLT). Of the 6 patients at dose level 2, 1 patient had DLT: Grade 3 thrombocytopenia resulting in a > 2-week delay in starting the next cycle of chemotherapy. Of the 6 patients at dose level 3, 1 patient had DLT: death due to pneumonia. There were 2 DLTs in the 7 patients at dose level 4: fever, neutropenia, and herpes zoster infection in 1 patient and death due to pneumonia in another. Seven patients had been started at dose level 5 when DLT was established at dose level 4: of the 5 fully evaluable and 2 partially evaluable patients at dose level 5, there was no DLT. CONCLUSIONS: The maximum tolerated dose of temozolomide and oral VP-16 in this heavily treated group of patients with recurrent malignant glioma is temozolomide 150 mg/m(2) per day for 5 days and oral VP-16 50 mg/m(2) per day for 12 days.

Acustimulation wristbands for the relief of chemotherapy-induced nausea.

CONTEXT: Substantial evidence suggests that acupuncture-point stimulation may be effective in controlling side effects of chemotherapy. OBJECTIVE: To examine the efficacy of an acustimulation wristband for the relief of chemotherapy-induced nausea. DESIGN: Randomized clinical trial using a 3-level crossover design. SETTING: Three outpatient oncology clinics in the northeastern United States. PARTICIPANTS: Twenty-five women and 2 men who experienced moderate or more severe nausea following their first chemotherapy treatment. INTERVENTION: We compared active acustimulation of the Pericardium 6 (PC-6) point on the ventral surface of the wrist with sham acustimulation (a corresponding point on the posterior surface of the wrist). A control group received no acustimulation. OUTCOME MEASURES: Severity of nausea and quantity of antiemetic medication used. RESULTS: No statistically significant differences in average severity of nausea were observed between the 3 interventions. However, the data showed a difference close to statistical significance in the severity of delayed nausea reported during active acustimulation compared to no acustimulation (P <.06). In addition, patients took fewer antinausea pills during the active-acustimulation cycle of this experiment compared to the no-acustimulation phase (P < .05). CONCLUSION: Findings on the efficacy of an acustimulation band for the control of chemotherapy-induced nausea are positive but not conclusive. These findings provide ample justification for further study of acustimulation in clinical oncology.

Temporal interrelationships among fatigue, circadian rhythm and depression in breast cancer patients undergoing chemotherapy treatment.

Seventy-eight female breast cancer patients were assessed for fatigue, depression, overall mood, and circadian rhythm at their second and fourth on-study chemotherapy cycles as part of a larger study examining the efficacy of paroxetine in reducing chemotherapy-induced fatigue. The Multidimensional Assessment of Fatigue (MAF), the Fatigue Symptom Checklist (FSCL), the Center for Epidemiologic Studies-Depression [CES-D) questionnaire, the Hamilton Depression Inventory (HDI), and the Profile of Mood States (POMS) were completed by patients at home 7 days after each treatment to assess symptom severity. Circadian rhythm was assessed over a 72-h period with the Mini-Motionlogger Actigraph (Ambulatory Monitoring, Ardsley, NY), starting 6 days after treatment. Daily patterns of sleep and activity were compared across the 3-day period by autocorrelation analyses to calculate a circadian rhythm score for each patient, with higher scores associated with lower disruption. Comparisons of fatigue, depression, and mood with patient circadian rhythm measures taken after the second cycle indicate that all five paper and pencil measures correlated well with the measure of circadian rhythm (all r(partial) <--0.30, all P<0.05). Changes in the fatigue, depression and mood measures from the second on-study treatment to the fourth were significantly correlated with concurrent changes in circadian rhythm (MAF r=-0.31; P=0.04; FSCL r=-0.30; P=0.04; CES-D r=-0.39; P=0.008; HDI r=-0.34; P=0.03; POMS r=-0.40; P=.007). These findings provide evidence that circadian rhythm disruption is involved in the experience of fatigue and depression in cancer patients.