Search

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. [ABSTRACT FROM AUTHOR]

Purpose: To update evidence-based guideline recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer., Methods: An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 545 articles. Outcomes of interest included efficacy and safety., Results: Of the 545 publications identified and reviewed, 14 were identified to form the evidentiary basis for the guideline recommendations., Recommendations: HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab deruxtecan for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations. There is a lack of head-to-head trials; therefore, there is insufficient evidence to recommend one regimen over another. The patient and the clinician should discuss differences in treatment schedule, route, toxicities, etc during the decision-making process. Options include regimens with tucatinib, trastuzumab emtansine, trastuzumab deruxtecan (if either not previously administered), neratinib, lapatinib, chemotherapy, margetuximab, hormonal therapy, and abemaciclib plus trastuzumab plus fulvestrant, and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4-6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive or progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone.Additional information is available at www.asco.org/breast-cancer-guidelines.

Purpose: To provide updated evidence- and consensus-based guideline recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer up to 2021., Methods: An Expert Panel conducted a targeted systematic literature review (for both systemic therapy for non-CNS metastases and for CNS metastases of HER2+ guideline updates) that identified 545 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events., Results: Of the 545 publications identified and reviewed, six on systemic therapy were identified to form the evidentiary basis for the systemic therapy for CNS metastases guideline recommendations., Recommendations: Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Memantine and hippocampal avoidance should be added to whole-brain radiotherapy when possible. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. There are insufficient data to recommend for or against performing routine magnetic resonance imaging to screen for brain metastases; clinicians should have a low threshold for magnetic resonance imaging of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer.Additional information is available at www.asco.org/breast-cancer-guidelines.

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.

Purpose To update the formal expert consensus-based guideline recommendations for practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2-positive advanced breast cancer to 2018. Methods An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 622 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. In 2014, the American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts, and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations. Results Of the 622 publications identified and reviewed, no additional evidence was identified that would warrant a change to the 2014 recommendations. Recommendations Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment in a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging to screen for brain metastases, but rather should have a low threshold for magnetic resonance imaging of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. Additional information is available at www.asco.org/breast-cancer-guidelines .

Purpose To update evidence-based guideline recommendations for practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer to 2018. Methods An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 622 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. Results Of the 622 publications identified and reviewed, no additional evidence was identified that would warrant a change to the 2014 recommendations. Recommendations HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab emtansine for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone. Additional information is available at www.asco.org/breast-cancer-guidelines .

Purpose: Mild-to-moderate bone pain is a commonly reported adverse event (AE) associated with pegfilgrastim. We evaluated the effect of prophylactic naproxen or loratadine vs no prophylactic treatment on pegfilgrastim-associated bone pain., Methods: In this open-label study (NCT01712009), women ≥ 18 years of age with newly diagnosed stage I-III breast cancer and an ECOG performance status ≤ 2 who were planning ≥ 4 cycles of adjuvant or neoadjuvant chemotherapy with pegfilgrastim support starting in cycle 1 were randomized 1:1:1 to receive naproxen, loratadine, or no treatment to prevent pegfilgrastim-associated bone pain. The primary endpoint was all-grade bone pain in cycle 1 from AE reporting. Secondary endpoints included bone pain in cycles 2-4 and across all cycles from AE reporting and patient-reported bone pain by cycle and across all cycles., Results: Six hundred patients were enrolled. Most patients (83.0%) were white, and mean (SD) age was 54.2 (11.1) years. The percentage of patients with all-grade bone pain in cycle 1 from AE reporting in the naproxen, loratadine, and no prophylaxis groups was 40.3, 42.5, and 46.6%, respectively; differences between the treatment groups were not statistically significant. Maximum, mean, and area under the curve for patient-reported bone pain were consistently lower in the naproxen and loratadine groups than in the no prophylaxis group; some of these differences were significant. Loratadine was associated with fewer treatment-related AEs and discontinuations than naproxen., Conclusions: Given its tolerability, its ease of administration, and its potential benefit, treatment with loratadine should be considered to help prevent bone pain in patients receiving chemotherapy and pegfilgrastim., Clinical Trial Registration: ClinicalTrials.gov ; NCT01712009.

Importance: In cancer clinical trials, symptomatic adverse events (AEs), such as nausea, are reported by investigators rather than by patients. There is increasing interest to collect symptomatic AE data via patient-reported outcome (PRO) questionnaires, but it is unclear whether it is feasible to implement this approach in multicenter trials., Objective: To examine whether patients are willing and able to report their symptomatic AEs in multicenter trials., Design, Setting, and Participants: A total of 361 consecutive patients enrolled in any 1 of 9 US multicenter cancer treatment trials were invited to self-report 13 common symptomatic AEs using a PRO adaptation of the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) via tablet computers at 5 successive clinic visits. Patient adherence was tracked with reasons for missed self-reports. Agreement with clinician AE reports was analyzed with weighted κ statistics. Patient and investigator perspectives were elicited by survey. The study was conducted from March 15, 2007, to August 11, 2011. Data analysis was performed from August 9, 2013, to March 21, 2014., Results: Of the 361 patients invited to participate, 285 individuals enrolled, with a median age of 57 years (range, 24-88), 202 (74.3%) female, 241 (85.5%) white, 73 (26.8%) with a high school education or less, and 176 (64.7%) who reported regular internet use (denominators varied owing to missing data). Across all patients and trials, there were 1280 visits during which patients had an opportunity to self-report (ie, patients were alive and enrolled in a treatment trial at the time of the visit). Self-reports were completed at 1202 visits (93.9% overall adherence). Adherence was highest at baseline and declined over time (visit 1, 100%; visit 2, 96%; visit 3, 95%; visit 4, 91%; and visit 5, 85%). Reasons for missing PROs included institutional errors in 27 of 48 (56.3%) of the cases (eg, staff forgetting to bring computers to patients at visits), patients feeling "too ill" in 8 (16.7%), patient refusal in 8 (16.7%), and internet connectivity problems in 5 (10.4%). Patient-investigator CTCAE agreement was moderate or worse for most symptoms (most κ < 0.05), with investigators reporting fewer AEs than patients across symptoms. Most patients believed that the system was easy to use (234 [93.2%]) and useful (230 [93.1%]), and investigators thought that the patient-reported AEs were useful (133 [94.3%]) and accurate (119 [83.2%])., Conclusions and Relevance: Participants in multicenter cancer trials are willing and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators. This approach may improve the precision of AE reporting in cancer trials.

Cancer care delivery in the United States is often fragmented and inefficient, imposing substantial burdens on patients. Costs of cancer care are rising more rapidly than other specialties, with substantial regional differences in quality and cost. The Centers for Medicare & Medicaid Services (CMS) Innovation Center (CMMIS) recently launched the Oncology Care Model (OCM), which uses payment incentives and practice redesign requirements toward the goal of improving quality while controlling costs. As of March 2017, 190 practices were participating, with approximately 3,200 oncologists providing care for approximately 150,000 unique beneficiaries per year (approximately 20% of the Medicare Fee-for-Service population receiving chemotherapy for cancer). This article provides an overview of the program from the CMS perspective, as well as perspectives from two practices implementing OCM: an academic health system (Yale Cancer Center) and a community practice (Hematology Oncology Associates of Central New York). Requirements of OCM, as well as implementation successes, challenges, financial implications, impact on quality, and future visions, are provided from each perspective.

Purpose: A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT)., Methods: A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data., Recommendations: The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Purpose A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). Methods A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. Recommendations The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

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.

Up to 50% of breast cancer survivors on aromatase inhibitor therapy report musculoskeletal symptoms such as joint and muscle pain, significantly impacting treatment adherence and discontinuation rates. We conducted a secondary data analysis of a nationwide, multi-site, phase II/III randomized, controlled, clinical trial examining the efficacy of yoga for improving musculoskeletal symptoms among breast cancer survivors currently receiving hormone therapy (aromatase inhibitors [AI] or tamoxifen [TAM]). Breast cancer survivors currently receiving AI (N = 95) or TAM (N = 72) with no participation in yoga during the previous 3 months were randomized into 2 arms: (1) standard care monitoring and (2) standard care plus the 4-week yoga intervention (2x/week; 75 min/session) and included in this analysis. The yoga intervention utilized the UR Yoga for Cancer Survivors (YOCAS©(®)) program consisting of breathing exercises, 18 gentle Hatha and restorative yoga postures, and meditation. Musculoskeletal symptoms were assessed pre- and post-intervention. At baseline, AI users reported higher levels of general pain, muscle aches, and total physical discomfort than TAM users (all P ≤ 0.05). Among all breast cancer survivors on hormonal therapy, participants in the yoga group demonstrated greater reductions in musculoskeletal symptoms such as general pain, muscle aches and total physical discomfort from pre- to post-intervention than the control group (all P ≤ 0.05). The severity of musculoskeletal symptoms was higher for AI users compared to TAM users. Among breast cancer survivors on hormone therapy, the brief community-based YOCAS©® intervention significantly reduced general pain, muscle aches, and physical discomfort., (© intervention significantly reduced general pain, muscle aches, and physical discomfort.)

Purpose: To provide formal expert consensus-based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer., Methods: The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations., Results: No studies or existing guidelines met the systematic review criteria; therefore, ASCO conducted a formal expert consensus-based process., Recommendations: Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging (MRI) to screen for brain metastases, but rather should have a low threshold for MRI of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer., (© 2014 by American Society of Clinical Oncology.)

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) occurs in as high as 70% of patients receiving certain types of chemotherapy agents. The FDA has yet to approve a therapy for CIPN. The aim of this multicenter, phase III, randomized, double-blind, placebo-controlled trial was to investigate the efficacy of 2% ketamine plus 4% amitriptyline (KA) cream for reducing CIPN., Methods: Cancer survivors who completed chemotherapy at least 1 month prior and had CIPN (>4 out of 10) were enrolled (N=462). CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average "pain, numbness, or tingling in [their] hands and feet over the past 24 h" on an 11-point numeric rating scale at baseline and 6 weeks post intervention. ANCOVA was used to measure differences in 6-week CIPN with effects including baseline CIPN, KA treatment arm, and previous taxane therapy (Y/N)., Results: The KA treatment showed no effect on 6-week CIPN scores (adjusted mean difference=-0.17, p=0.363)., Conclusions: This study suggests that KA cream does not decrease CIPN symptoms in cancer survivors.

Purpose: To provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer., Methods: The American Society of Clinical Oncology convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic literature review from January 2009 to October 2012. Outcomes of interest included overall survival, progression-free survival (PFS), and adverse events., Results: A total of 16 trials met the systematic review criteria. The CLEOPATRA trial found survival and PFS benefits for docetaxel, trastuzumab, and pertuzumab in first-line treatment, and the EMILIA trial found survival and PFS benefits for trastuzumab emtansine (T-DM1) in second-line treatment. T-DM1 also showed a third-line PFS benefit. One trial reported on duration of HER2-targeted therapy, and three others reported on endocrine therapy for patients with HER-positive advanced breast cancer., Recommendations: HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and T-DM1 for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or T-DM1 (if not previously administered) and may offer pertuzumab, if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone., (© 2014 by American Society of Clinical Oncology.)

Purpose: We assessed adding the multikinase inhibitor sorafenib to gemcitabine or capecitabine in patients with advanced breast cancer whose disease progressed during/after bevacizumab., Experimental Design: This double-blind, randomized, placebo-controlled phase IIb study (ClinicalTrials.gov NCT00493636) enrolled patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer and prior bevacizumab treatment. Patients were randomized to chemotherapy with sorafenib (400 mg, twice daily) or matching placebo. Initially, chemotherapy was gemcitabine (1,000 mg/m(2) i.v., days 1, 8/21), but later, capecitabine (1,000 mg/m(2) orally twice daily, days 1-14/21) was allowed as an alternative. The primary endpoint was progression-free survival (PFS)., Results: One hundred and sixty patients were randomized. More patients received gemcitabine (82.5%) than capecitabine (17.5%). Sorafenib plus gemcitabine/capecitabine was associated with a statistically significant prolongation in PFS versus placebo plus gemcitabine/capecitabine [3.4 vs. 2.7 months; HR = 0.65; 95% confidence interval (CI): 0.45-0.95; P = 0.02], time to progression was increased (median, 3.6 vs. 2.7 months; HR = 0.64; 95% CI: 0.44-0.93; P = 0.02), and overall response rate was 19.8% versus 12.7% (P = 0.23). Median survival was 13.4 versus 11.4 months for sorafenib versus placebo (HR = 1.01; 95% CI: 0.71-1.44; P = 0.95). Addition of sorafenib versus placebo increased grade 3/4 hand-foot skin reaction (39% vs. 5%), stomatitis (10% vs. 0%), fatigue (18% vs. 9%), and dose reductions that were more frequent (51.9% vs. 7.8%)., Conclusion: The addition of sorafenib to gemcitabine/capecitabine provided a clinically small but statistically significant PFS benefit in HER2-negative advanced breast cancer patients whose disease progressed during/after bevacizumab. Combination treatment was associated with manageable toxicities but frequently required dose reductions., (©2013 AACR)

Gabapentin is used for the treatment of hot flashes and neuropathic pain in breast cancer survivors, and is commonly used off-label for the treatment of anxiety. Yet, clinical trial evidence to support the use of gabapentin for anxiety symptoms is lacking. In a randomized, double-blinded controlled trial we compared 300 mg gabapentin versus 900 mg gabapentin versus placebo. Subjects were 420 breast cancer patients who had completed all chemotherapy cycles. Anxiety traits and current (state) anxiety were measured using the Speilberger Strait-Trait Anxiety Inventory at baseline, 4 and 8 weeks. Pain was measured at baseline using a 10-point scale. Analyses included analysis of covariance and ordinary least squares regression. At 4 weeks, state anxiety change scores were significantly better for gabapentin 300 and 900 mg (p = 0.005) compared to placebo. The magnitude of improvement was proportional to baseline state anxiety. At 8 weeks, the anxiolytic effects of gabapentin compared to placebo persisted (p < 0.005). We found no significant interactions. The lower dose (300 mg) was associated with the best treatment outcomes for all patients except those with the highest baseline anxiety. Given its similar pharmacology, efficacy in the treatment of hot flashes, and low cost, gabapentin may provide a low cost and parsimonious alternative treatment choice for breast cancer survivors presenting in primary care practices with anxiety symptoms. Gabapentin is effective for hot flashes, and, therefore, may provide therapeutic benefit for both anxiety and hot flashes at a generic drug price. For patients reluctant to take a controlled substance, such as a benzodiazepine, gabapentin may offer an alternative therapy. Similarly, patients with a history of substance use may benefit from gabapentin without risk of addiction or abuse. For cancer survivors experiencing both hot flashes and anxiety, gabapentin may provide a single effective treatment for both and is an alternative therapy for anxiety for patients unwilling to take a benzodiazepine or those with a history of substance use.

Purpose: Pegfilgrastim-induced bone pain is a significant clinical problem that may result in discontinuation of pegfilgrastim and lead to less effective chemotherapy dosing. Interventions for pegfilgrastim-induced bone pain are needed., Patients and Methods: The University of Rochester Cancer Center Clinical Community Oncology Program Research Base randomly assigned 510 patients at 17 sites to receive either naproxen (500 mg two times per day) or placebo on the day of pegfilgrastim administration, continuing for 5 to 8 days after pegfilgrastim. Patients recorded pain severity (using a scale of 0 to 10) and duration in daily diaries. The primary outcome measure was the area under the curve (AUC) for pain for days 1 through 5. Secondary outcome measures included the identification of risk factors for the development of pain and response to naproxen., Results: Patients' mean age was 55.6 years and 86% were female. Sixty-eight percent of patients had breast cancer and 10% had lung cancer. Pain reached its peak at 3 days for both groups. The mean AUC for pain was 7.71 for the placebo group and 6.04 for the naproxen group (P = .037). Naproxen reduced maximum pain from 3.40 to 2.59 (P = .005). Naproxen also reduced overall pain incidence from 71.3% to 61.1% (P = .020) and duration from 2.40 to 1.92 days (P = .009). The reduction in severe pain (> 5 on a scale of 1 to 10) from 27.0% to 19.2% was also significant (P = .048). Risk factors could not be identified to predict incidence, severity, or ability to prevent pegfilgrastim-induced bone pain., Conclusion: Our phase III randomized placebo-controlled clinical trial demonstrated that naproxen at a dose of 500 mg twice per day is effective in reducing the incidence and severity of pegfilgrastim-induced bone pain.

Background: Race/ethnicity and culture influence illness perceptions, health beliefs and behaviors, and communication with health care providers. However, information about the impact of race/ethnicity on the understanding of cancer diagnosis and treatment plan is limited., Methods: Nine hundred seventy-three cancer patients completed an information needs-assessment questionnaire prior to starting treatment at 20 geographically distinct clinical cancer sites within the University of Rochester Community Clinical Oncology Program network. Chi2 Test was used to examine the association between race/ethnicity and education, occupation, and perception and use of available information. T test and analysis of covariance were used to examine race/ethnicity-based differences in concerns over understanding cancer diagnosis/treatment plan and the effect of race/ethnicity controlling for demographics., Results: There were 904 non-Hispanic white and 69 nonwhite (blacks, Latinos, and others) patients in the sample. Whites and nonwhites were comparable in educational attainment and occupation. However, there was a statistically significant race/ethnicity-based difference in concerns over understanding the diagnosis and treatment plan for cancer, even after controlling for sex (male, female), age, education, and occupation (p < .001). More nonwhite patients indicated that additional information would have been helpful in dealing with these concerns (p <.001)., Conclusions: Nonwhite cancer patients reported more concerns about understanding their diagnosis and treatment plan and were more likely to indicate that additional information would have been helpful. The findings emphasize the need for oncology professionals to confirm patients' understanding and ensure patients' information needs have been met, particularly when working with racial/ethnic minorities.

The purpose of this study was to develop and validate a self-report measure of body image and sexual adjustment in breast cancer patients: the Sexual Adjustment and Body Image Scale (SABIS). Three hundred and fifty three women diagnosed with primary breast cancer that had completed initial surgical treatment completed the SABIS and five measures of psychological, psychosocial, and sexual functioning. Psychometric properties of the SABIS were examined and it was found to be a reliable and valid means of assessing body image and sexuality in breast cancer patients following surgery.

Several studies have shown that patients' expectancies for the development of nausea following chemotherapy are robust predictors of that treatment-related side effect, and some studies have shown that interventions designed to influence expectancies can affect patients' reports of symptoms. In this randomized, multicenter, Community Clinical Oncology Program trial, we investigated the effect of an expectancy manipulation designed to reduce nausea expectancy on chemotherapy-induced nausea in 358 patients scheduled to receive chemotherapy treatment. Patients in the intervention arm received general cancer-related educational material plus specific information about the efficacy of ondansetron, specifically designed to diminish nausea expectancy. Patients in the control arm received only the general cancer-related educational material. Nausea expectancy was assessed both prior to and following the educational intervention. We observed a significant reduction in nausea expectancy in the intervention group (P=0.024) as compared to the control group (P=0.34). In the intervention group, patients' expectations of nausea assessed prior to the intervention correlated significantly with average nausea (r=0.27, P=0.001), whereas nausea expectancy assessed following the intervention did not (r=0.1, P=0.22). Although the expectancy manipulation reduced patients' reported expectations for the development of nausea, the occurrence of nausea was not reduced. Furthermore, post-intervention nausea expectancy compared to pre-intervention expectancy was less predictive of subsequent nausea. Explanations for these findings include the possibility that the expectancy manipulation was not strong enough, and the possibility that changing nausea expectancies does not change occurrence of nausea.

The purpose of this study was to explore the relative contributions of coping, depression, pain and age, in the experience of cancer related fatigue. A total of 353 women treated for primary breast cancer were assessed within one year of diagnosis using the Profile of Mood States, the Hospital Anxiety and Depression Scale and the mini-Mental Adjustment to Cancer Scale. Fatigue was positively associated with depression and pain, but inversely related to age. In contrast to our expectations, fighting spirit was not associated with less fatigue. A relationship between coping style and cancer-related fatigue was found exclusively for 'positive reappraisal', a combination of fighting spirit and fatalism. Detectable only in multivariate analysis together with depression, the results suggest a weak association between coping and fatigue. The relationship between cancer related fatigue, age and coping styles requires further exploration within longitudinal studies., (Copyright 2005 John Wiley & Sons, Ltd.)

Goals of Work: To assess complementary and alternative medicine (CAM) therapies being utilized by cancer patients during treatment and communication about CAM usage between the patient and physician., Patients and Methods: Newly diagnosed cancer patients receiving chemotherapy or radiation therapy were recruited to complete a CAM survey within 2 weeks after the termination of treatment. Patients were queried on which CAM modalities they utilized and whether or not they were discussed with either their oncologist or primary care physician., Main Results: Of the patients surveyed, 91% reported using at least one form of CAM. The most widely used forms of CAM were prayer, relaxation and exercise. CAM users tended to be women chemotherapy patients with at least a high school education. Of the patients using CAM, 57% discussed the use of at least one of these therapies with their oncologist or primary care physician. The most frequent CAM modalities discussed with at least one physician were diets, massage, and herbal medicine., Conclusions: An overwhelming proportion of cancer patients are using CAM, particularly prayer, relaxation, and exercise. However, patients may not discuss the use of CAMs at all or fully with their physician; if they do, it is most likely to be their oncologist, but not about the most frequently used CAMs. Future research needs to assess effective ways for oncologists to gather information about CAM usage by patients during allopathic treatment and discern ways these therapies may enhance or interfere with traditional cancer treatments.

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.

We evaluated therapy with weekly paclitaxel 80 mg/m2 in metastatic breast cancer patients age > or =65. There was a low incidence of serious toxicities, with similar tolerability profiles in younger and older patients. Response rates and overall survival times were comparable in the two age groups (<65 and > or =65). Weekly paclitaxel therapy is a reasonable option for older patients with metastatic breast cancer.

Purpose: We evaluated the safety and efficacy of weekly paclitaxel therapy in women with metastatic breast cancer in a phase II multicenter trial. Entry criteria were relatively liberal to reflect the heterogeneity of metastatic breast cancer in clinical practice., Patients and Methods: Patients had histologically confirmed and measurable metastatic breast cancer. Up to two prior chemotherapy regimens for metastatic disease, including prior therapy with anthracyclines and taxanes and prior high-dose therapy, were allowed. Paclitaxel 80 mg/m(2) was administered weekly for 4 weeks per 4-week cycle., Results: We enrolled 212 patients; 211 were assessable for toxicity and 177 were assessable for response. Ninety percent of patients had received prior chemotherapy (adjuvant, metastatic, or both), 46% of patients had three or more involved metastatic sites, and 60% of patients had visceral-dominant disease. Responses were documented on two occasions and were independently reviewed. The overall response rate (complete plus partial response) was 21.5% (95% confidence interval, 15.4% to 27.5%), with 41.8% of patients having disease stabilization. Median time to progression was 4.7 months, and overall survival in all 212 patients enrolled was 12.8 months. Therapy was well tolerated, with a 15% incidence of grade 3/4 hematologic toxicity and a 9% incidence of grade 3 neurotoxicity; other serious toxicities were rare. The response rate and toxicity profile in the 34% of patients > or = 65 years of age were similar to that of younger patients., Conclusion: Weekly paclitaxel therapy was well tolerated and demonstrated reasonable activity in this relatively heavily pretreated population with advanced disease. Further study of weekly paclitaxel in combination therapy is warranted.

Objective: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axillary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are intended for use in the care of patients outside of clinical trials., Potential Intervention: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated., Outcomes: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity., Evidence: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed., Values: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A "recommendation" was made when level I or II evidence was available and there was consensus as to its meaning. A "suggestion" was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus., Recommendations: The recommendations, suggestions, and expert opinions of the Panel are described in this article., Validation: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document.

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.

The purpose of this study was to determine the maximum tolerated dose and dose-limiting toxicities of fish oil fatty acid capsules containing omega-3 fatty acid ethyl esters. Twenty-two patients with neoplastic disease not amenable to curative therapy who had lost 2% of body weight over a previous 1 month time period were given an escalating dose of fish oil fatty acids. The maximum tolerated dose was found to be 0.3 g/kg per day of this preparation. This means that a 70-kg patient can generally tolerate up to 21 1-g capsules/day containing 13.1 g of eicosapentaenoic acid + docosahexaenoic acid, the two major omega-3 fatty acids. Dose-limiting toxicity was gastrointestinal, mainly diarrhea, and a poorly described toxicity designated as "unable to tolerate in esophagus or stomach." A patient with chronic lymphocytic leukemia taking the fish oil provided an unusual opportunity to perform a detailed biochemical study of the effect of fish oil capsules on the lipids of malignant cells at several sequential time points in treatment. Studies of the malignant lymphocytes, serum, and whole blood of this one patient revealed an increase in eicosapentaenoic acid, the major component of the fish oil capsules, during fish oil capsule treatment. This study provides a scientific basis for the selection of omega-3 fatty acid doses for future studies in cancer. The maximum tolerated dose found is considerably higher than anticipated from published studies of many human diseases. The observation of a modification of the lipids of leukemic cells, serum, and blood in a patient with chronic leukemia provides a biochemical basis for a possible effect of fish oil supplements on cancer cachexia and tumor growth.

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.

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.

This study evaluated a training program for leaders of supportive-expressive psychotherapy groups for breast cancer patients. Twenty-four mental health/medical cancer care professionals completed two training phases and were tested for their understanding of the treatment model. Participants' understanding was enhanced as a result of the training program. This study demonstrates that a brief training program can improve therapists' understanding of the treatment model and demonstrates an effective method of evaluation. Future research should examine how performance on these tests generalizes to performance when leading a supportive-expressive group.

Malignant meningiomas are uncommon and rarely occur outside the central nervous system. We describe herein a morphologically unusual malignant neoplasm that arose in the retroperitoneum of a 25-year-old woman. The tumor was composed of sheets of epithelioid cells that were frequently arranged in prominent whorls. By electron microscopy, the neoplastic cells had long, tapering cell processes that formed numerous interdigitations; many junctions including desmosomes; and abundant intermediate filaments. Immunohistochemistry showed that the tumor cells expressed vimentin, keratin, and epithelial membrane antigen. Based on these findings, the neoplasm was classified as a malignant meningioma. According to our review of the literature, this is the first reported occurrence of a primary retroperitoneal meningothelial neoplasm and the second reported case of an ectopic meningioma that was malignant.

Background: In a pilot study, Cancer and Leukemia Group B (CALGB) incorporated etoposide into primary combination therapy for advanced Hodgkin disease., Methods: Thirty-six evaluable patients were treated with two or three courses of methotrexate, vincristine, prednisone, leucovorin, etoposide, and cyclophosphamide (MOPLEC), and then treated with five to seven additional courses of a known "curative" regimen: nitrogen mustard, vinblastine, prednisone, and procarbazine (MVPP)., Results: After treatment with MOPLEC, there were 16 complete responders (44%) and 18 partial responders (50%). One patient had progressive disease and one patient was taken off study after an anaphylactic reaction to etoposide. After completing the entire protocol, 32 patients achieved complete remission (CR) (89%) and 3 achieved partial remission (PR) (8%). Five CR patients have relapsed and three additional patients have died in CR without recurrence. At 36 months, the estimated failure-free survival is 61% and overall survival is 72%., Conclusions: This combination, which includes etoposide, is active for the primary treatment of advanced Hodgkin disease.

Four types of colonies can be formed by progenitor cells (CFUc) in double layer agar cultures: eosinophil, granulocyte, macrophage, and mixed granulocyte-macrophage. We have developed a method for in situ staining of intact agar plates with luxol fast blue and acetoorcein employed to differentiate the type of colonies. Cultures of 10(5) normal human bone marrow cells yielded 89.1 colonies, of which 72% were eosinophil. Cultures of 5 X 10(5) peripheral blood cells, enriched by isopycnic sedimentation, yielded 39.0 colonies, of which 48% were eosinophil. T-cell depleted peripheral blood mononuclear cells yielded 116.9 colonies/5 X 10(5) cells, of which 74% were eosinophil. Umbilical cord blood cells yielded 65.1 colonies/5 X 10(5) cells, of which 23% were eosinophil. Comparing similar numbers of total colonies, there appears to be fewer relative and absolute numbers of eosinophil colonies formed by CFUc recovered from cord blood as opposed to adult peripheral blood and bone marrow. Enumeration of colony numbers without regard to types of colonies is imprecise. The method employed in the present study is easy to perform, reproducible and provides permanent slides.

HTLV-I is associated with adult T-cell leukemia/lymphoma (ATL) characterized by monoclonal expansions of CD4+ T-lymphocytes. In this report we describe a histologically benign, polyclonal HTLV-I infection in a patient exhibiting both an absolute CD4+ and CD8+ lymphocytosis. Three T-cell lines containing integrated HTLV-I proviral copies established from this patient were initially polyclonal, but with time all grew out the same two clones as determined by analysis of their T-cell antigen receptor beta chain gene rearrangements. The patient subsequently developed pulmonary and nasopharyngeal nodules containing HTLV-I infected cells. Restriction analysis of the patient's HTLV-I provirus revealed no differences from prototype HTLV-I and the tax gene was normally expressed in vivo and in vitro. The patient's T-lymphocytosis and HTLV-I+ pulmonary tract nodules were put into a complete clinical remission by treatment with alkylating agents and steroids. Subsequently, the patient developed a severe immunodeficiency state and expired. Retrospective serologic and gene amplification assays for HIV-1 demonstrated that he had been doubly infected from the time of presentation. Postmortem analysis by polymerase chain reaction revealed the presence of both HTLV-I and HIV-1 in lymphatic tissues and the testes; HIV-1 was also detected in brain tissue.

Twenty-five patients from the literature and two additional patients with Hodgkin's disease and idiopathic thrombocytopenic purpura (ITP) are reviewed. In 22 patients the ITP occurred after the Hodgkin's disease was treated. In nine of these patients, the Hodgkin's disease. In one patient, ITP preceded Hodgkin's disease by one year. Seven of 26 patients achieved complete remission of the ITP with prednisone. In each of these patients the Hodgkin's disease was in complete remission, and each had a previous splenectomy. Seven of 14 patients achieved complete remission of the ITP after splenectomy. Four of these patients had active Hodgkin's disease. Of the 27 patients, 14 were in remission of the Hodgkin's disease at the time of ITP. To date, relapse of the Hodgkin's disease had occurred in only one patient. Lymphadenopathy in five of these patients proved to be benign hyperplasia on biopsy. In addition to the association with Hodgkin's disease, review of ITP cases at Upstate Medical Center and a recent report in the literature indicate that there may be a general association between ITP and malignancy.

A double-layer agar culture assay for granulopoietic progenitor cell (CFU-C) was employed to study the in vitro growth pattern of bone marrow or peripheral blood cells from 37 patients at diagnosis of acute nonlymphocytic leukemia. The patients were classified as having type A growth if there were greater than 50 colonies (A1), or greater than one colony and greater than 50 clusters was observed after 14 days in culture (A2). Type B growth was defined as no growth (B1), less than 50 colonies and less than 50 clusters (B2) or cluster growth only (B3). Agar cultures containing marrow cells from 10 patients were stained in situ, and the colonies and clusters revealed abnormal cellular maturation. Treatment with cytosine arabinoside and an anthracycline resulted in a complete remission of leukemia in one of 15 patients with type A growth and 17 of 22 patients with type B growth. The subtype of growth pattern did not correlate with the mechanism (i.e., drug resistance versus kinetic resistance) for the failure to achieve a complete remission. The subtype of type B growth (B1, B2 or B#) did not correlate with the duration of complete remission. Nonetheless, the growth patterns observed in cultures of cells obtained from patients with acute nonlymphocytic leukemia appear to be excellent predictors of the success of achieving complete remission with induction therapy.

A 51-year-man was seen with the diagnosis of acute myelomonocytic leukemia. The WBC count was 380,000/microL at presentation. The serum phosphorus concentration was 0.4 mg/dL and 0.2 mg/dL prior to any phosphorus replacement. Urinary phosphorus excretion was too low to be measured. The patient did not demonstrate any of the usual causes of profound hypophosphatemia with hypophosphaturia. The parathyroid glands were normal at necropsy. Reasons for believing the profound hypophosphatemia was due to phosphorus uptake by the leukemic cells are discussed.

The pathophysiology of a neutropenic disorder was evaluated in a 60-year-old man using myeloid progenitor cell (CFU-C), colony stimulating activity (CSA), and antineutrophil antibody assays. An immunoglobulin, present in the patient's serum at presentation, was directed against peripheral blood neutrophils, and autologous and allogeneic bone marrow CFU-C. A course of prednisone resulted in resolution of the neutropenia and a disappearance of the cytotoxic antibody. This study suggests that the patient's neutropenic disorder resulted from antibody-mediated destruction of circulating neutrophils and a suboptimal bone marrow granulopoietic response.

Primary germ cell neoplasms of the central nervous system (CNS) are rare tumors which generally respond to radiotherapy. Experience is limited in managing the refractory patient. We report a patient whose suprasellar dysgerminoma responded completely to 5,000 rad. Seven years later, disease recurrence was refractory to an additional 4,000 rad. Theorizing that the "blood-brain barrier" was no longer intact after extensive radiotherapy and tumor involvement of the ventricular system, the patient was treated with systemic bleomycin, cisplatin, and vinblastine. Pharmacokinetic studies revealed that the bleomycin and cisplatin entered the cerebrospinal fluid. Serial CT scans and CSF levels of beta-HCG confirmed the clinical impression of a partial remission. Subsequent tumor progression was refractory to therapy with intraventricular bleomycin. It is concluded that systemic chemotherapy may be beneficial in certain cases of CNS germ cell neoplasms.