Jeffrey J. Kirshner

Hydrocortisone With or Without Mitoxantrone in Men With Hormone-Refractory Prostate Cancer: Results of the Cancer and Leukemia Group B 9182 Study

PURPOSE Approximately 40,000 men die each year of hormone-refractory prostate cancer (HRPC). The results of treatment with chemotherapy have been disappointing to date, with no trials demonstrating a benefit with respect to survival duration. Corticosteroids and mitoxantrone each have been shown to be active agents in this disease. The purpose of this study was to demonstrate an advantage of mitoxantrone and hydrocortisone (M+H) over hydrocortisone alone with respect to survival duration. PATIENTS AND METHODS Two hundred forty-two patients with HRPC were randomized to receive either M+H or hydrocortisone alone. Patients were monitored for survival, time to disease progression, time to treatment failure, response, and quality-of-life (QOL) parameters. RESULTS Treatment in both arms was well tolerated. Although there was a delay in time to treatment failure and disease progression in favor of M+H over hydrocortisone alone, there was no difference in overall survival (12.3 months for M+H v 12.6 months for hydrocortisone alone). There was an indication that QOL was better with M+H, in particular with respect to pain control. CONCLUSION M+H generated more frequent responses and a delay in both time to treatment failure and disease progression compared with hydrocortisone alone. In addition, there was a possible benefit of M+H with respect to pain control over hydrocortisone alone. No improvement in survival was observed. Although M+H could be viewed as a palliative option for patients with HRPC, new drugs and novel strategies are needed to improve survival for this disease.

Differential Effects of Paroxetine on Fatigue and Depression: A Randomized, Double-Blind Trial From the University of Rochester Cancer Center Community Clinical Oncology Program

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

Adult idiopathic thrombocytopenic purpura: Clinical findings and response to therapy

Abstract Sixty-two adults with idiopathic thrombocytopenic purpura were seen from 1971 to 1979. All were >16 years old, with 150,000/μl). In 75 percent of the patients, complete remission was achieved by six weeks. Only 29 percent of those with a complete remission (complete responders) are projected to be in a continuing remission after 48 months. The majority of relapses occurred during the first two years of remission. A symptom duration of

Implementing a Geriatric Assessment in Cooperative Group Clinical Cancer Trials: CALGB 360401

PURPOSE Factors captured in a geriatric assessment can predict morbidity and mortality in older adults, but are not routinely measured in cancer clinical trials. This study evaluated the implementation of a geriatric assessment tool in the cooperative group setting. PATIENTS AND METHODS Patients age ≥ 65 with cancer, who enrolled on cooperative group cancer trials, were eligible to enroll on Cancer and Leukemia Group B (CALGB) 360401. They completed a geriatric assessment tool before initiation of protocol therapy, consisting of valid and reliable geriatric assessment measures which are primarily self-administered and require minimal resources and time by healthcare providers. The assessment measures functional status, comorbidity, cognitive function, psychological state, social support, and nutritional status. The protocol specified criteria for incorporation of the tool in future cooperative group trials was based on the time to completion and percent of patients who could complete their portion without assistance. Patient satisfaction with the tool was captured. RESULTS Of the 93 patients who enrolled in this study, five (5%) met criteria for cognitive impairment and three did not complete the cognitive screen, leaving 85 assessable patients (median age, 72 years). The median time to complete the geriatric assessment tool was 22 minutes, 87% of patients (n = 74) completed their portion without assistance, 92% (n = 78) were satisfied with the questionnaire length, 95% (n = 81) reported no difficult questions, and 96% (n = 82) reported no upsetting questions. One hundred percent of health care professionals completed their portion. CONCLUSION This brief, primarily self-administered geriatric assessment tool met the protocol specified criteria for inclusion in future cooperative group clinical trials.

Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

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.

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.

Information-Seeking Styles Among Cancer Patients Before and After Treatment by Demographics and Use of Information Sources

The type and quantity of information needed varies between patients who actively seek information and those who tend to avoid information.We analyzed data from a longitudinal study of adult cancer patients from outpatient clinics for whom information needs and behaviors were assessed by survey before and after treatment. We evaluated the relationships between information-seeking style (active, moderately active, and passive styles) and demographics, cancer type, and health status for the pretreatment and posttreatment periods and overall. The generalized estimating equations (GEE) approach was used to model the log odds of more active to more passive information-seeking preferences taking into consideration both the pretreatment and posttreatment periods. Analyses included 731 case participants, including female breast cancer patients (51%), male genitourinary cancer patients (18%), and lung cancer patients of both sexes (10%). At pretreatment, 17% reported an active information-seeking style, 69% were moderately active, and 14% were passive. During this period, 19% of those with at least some college education reported being very active compared with 14% of those with less education. With adjustment for all other covariates, male genitourinary and lung cancer patients had a higher odds of having a more active information-seeking style in the pretreatment than in the posttreatment period, with an odds of 4.5 (95% confidence interval [CI]: 2.4–8.4) and 5.4 (95% CI: 2.7–10.6), respectively. Controlling for all covariates, breast cancer patients had 1.5 (95% CI: 1.0–2.1) times higher odds of being more active in seeking information than other patients. Public health researchers and clinicians must work together to develop the most effective strategy for meeting the informational needs of these patients before and after treatment.

Recommendations on Disease Management for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: American Society of Clinical Oncology Clinical Practice Guideline

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.

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.

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.

Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: Final results from CALGB trial 79809

BACKGROUND Chemotherapy-induced ovarian failure (CIOF) is a frequent side-effect of adjuvant chemotherapy that results in rapid bone loss. We hypothesised that zoledronic acid (ZA), a third-generation amino bisphosphonate, would prevent bone loss in premenopausal women who developed CIOF. METHODS Women (439) were randomised to intravenous (i.v.) ZA 4 mg every 3 months for 2 years starting within 1-3 months after randomization (arm A) or 1 year after randomization (arm B, controls). CIOF was prospectively defined as ≥ 3 months of amenorrhoea, follicle-stimulating hormone (FSH) ≥ 30 MIU/ml and non-pregnant at 1 year. The primary end-point was the percentage change in bone mineral density (BMD) in the lumbar spine (LS) from baseline to 12 months in the ZA and in control groups in women who developed CIOF; the secondary end-point was BMD in LS at 3 years in all randomised women. FINDINGS One hundred and fifty (56%) met the definition of CIOF at 1 year. Overall, grade 3 toxicities of ZA were fatigue (1%) arthralgias (21%) and pain (84%). The median percent change (interquartile range, IQR) at 1 year was +1.2% (-0.5% to +2.8%) and -6.7% (-9.7% to -2.9%) p<0.001 and at 3 years was +1.0% (-1.6% to +5.2%) and -0.5% (-3.7% to +3.2%) p=0.019 in arms A and B, respectively. INTERPRETATION ZA every 3 months is well tolerated and prevents rapid bone loss in premenopausal women that develop CIOF. Giving ZA with rather than 1 year after the start of adjuvant chemotherapy is the preferred sequence to prevent bone loss.