Aminah Jatoi

Dronabinol Versus Megestrol Acetate Versus Combination Therapy for Cancer-Associated Anorexia: A North Central Cancer Treatment Group Study

PURPOSE To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia. PATIENTS AND METHODS Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight. RESULTS Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P =.0001) for appetite and 11% versus 3% (P =.02) for > or = 10% baseline weight gain. Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone. The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate-treated and combination-treated patients. The single-item Uniscale, a global QOL instrument, found comparable scores. Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate. CONCLUSION In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone. Combination therapy did not appear to confer additional benefit.

Muscle wasting in cancer cachexia: clinical implications, diagnosis, and emerging treatment strategies.

Cancer cachexia is a complex metabolic condition characterized by loss of skeletal muscle. Common clinical manifestations include muscle wasting, anemia, reduced caloric intake, and altered immune function, which contribute to increased disability, fatigue, diminished quality of life, and reduced survival. The prevalence of cachexia and the impact of this disorder on the patient and family underscore the need for effective management strategies. Dietary supplementation and appetite stimulation alone are inadequate to reverse the underlying metabolic abnormalities of cancer cachexia and have limited long-term impact on patient quality of life and survival. Therapies that can increase muscle mass and physical performance may be a promising option; however, there are currently no drugs approved for the prevention or treatment of cancer cachexia. Several agents are in clinical development, including anabolic agents, such as selective androgen receptor modulators and drugs targeting inflammatory cytokines that promote skeletal muscle catabolism.

Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes: Results of a placebo-controlled trial from the North Central Cancer Treatment Group (N03CB)

Epidermal growth factor receptor (EGFR) inhibitors are effective cancer therapies, but they are reported to cause a rash in >50% of patients. In the current study, the authors examined the use of tetracycline for rash prevention.

Complete Pathologic Response After Neoadjuvant Chemoradiotherapy for Esophageal Cancer Is Associated With Enhanced Survival

BACKGROUND Neoadjuvant chemoradiotherapy followed by esophagogastrectomy has become the standard of care for patients with locally advanced esophageal cancer. This report analyzes our experience with this treatment approach. METHODS From January 1998 through December 2003, all patients from a single institution receiving neoadjuvant chemoradiotherapy followed by esophagogastrectomy were reviewed for operative mortality, morbidity, long-term survival, and factors affecting survival. Only patients preoperatively staged with both computed tomographic scans and endoscopic ultrasound were included. RESULTS There were 162 patients (142 men, 20 women), and the median age was 61 years (range, 22 to 81 years). Histopathology was adenocarcinoma in 143 patients and squamous cell in 19. Pretreatment clinical stage was II in 28 patients (17%), III in 111 (68%), and IV (M1a) in 23 (14%). Ivor Lewis esophagogastrectomy was the most common procedure, occurring in 132 patients. Operative mortality and morbidity was 4.9% and 37%, respectively. Pathologic response was complete in 42 patients (26%), near complete in 27 (17%), partial in 88 (54%), and unresectable in 5 (3%). Five-year survival for overall, complete, near complete, and partial response patients was 34%, 55%, 27%, and 27%, respectively (p = 0.013). Patients whose lymph nodes were rendered free of cancer showed improved overall and disease-free survival compared with patients having persistently positive lymph nodes (p = 0.019). CONCLUSIONS Esophagogastrectomy after neoadjuvant chemoradiotherapy can be performed with low mortality and morbidity. Patients with complete pathologic response have significantly improved long-term survival compared with patients with near complete and partial responses. Future efforts should be directed at understanding determinants of complete responses.

Current management strategies for ovarian cancer

Epithelial ovarian cancer originates in the layer of cells that covers the surface of the ovaries. The disease spreads readily throughout the peritoneal cavity and to the lymphatics, often before causing symptoms. Of the cancers unique to women, ovarian cancer has the highest mortality rate. Most women are diagnosed as having advanced stage disease, and efforts to develop new screening approaches for ovarian cancer are a high priority. Optimal treatment of ovarian cancer begins with optimal cytoreductive surgery followed by combination chemotherapy. Ovarian cancer, even in advanced stages, is sensitive to a variety of chemotherapeutics. Although improved chemotherapy has increased 5-year survival rates, overall survival gains have been limited because of our inability to eradicate all disease. Technologic advances that allow us to examine the molecular machinery that drives ovarian cancer cells have helped to identify numerous therapeutic targets within these cells. In this review, we provide an overview of ovarian cancer with particular emphasis on recent advances in operative management and systemic therapies.

Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma

Introduction: The EML4–anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors. Methods: We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated. Results: ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/− assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases. Conclusions: Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.

A placebo-controlled, double-blind trial of infliximab for cancer-associated weight loss in elderly and/or poor performance non-small cell lung cancer patients (N01C9)

PURPOSE This study tested whether infliximab, a chimeric IgG1kappa monoclonal antibody that blocks tumor necrosis factor (TNF) alpha, improves/stabilizes weight loss in elderly and/or poor performance status patients with metastatic non-small cell lung cancer (NSCLC). METHODS This double-blind trial randomly assigned patients to infliximab/docetaxel (n=32) versus placebo/docetaxel (n=29). The primary endpoint was > or = 10% weight gain. RESULTS Groups were balanced with respect to age, number of prior chemotherapy regimens, baseline weight loss, and performance status. No patient gained > or = 10% baseline weight, and early evidence of the lack of efficacy prompted early trial closure. Appetite improvement was negligible in both arms. However, infliximab-/docetaxel-treated patients developed greater fatigue and worse global quality of life scores. Other outcomes, such as tumor response rate (<10% in both groups) and overall survival, were not statistically different between groups. There were no statistically significant differences in adverse events, although one death was attributed to infliximab. Genotyping for the TNF alpha -238 and -308 polymorphisms revealed no clinical significance of these genotypes, as relevant to the loss of weight or appetite. CONCLUSIONS This trial closed early because infliximab did not prevent or palliate cancer-associated weight loss. Infliximab was associated with increased fatigue and inferior global quality of life.

A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome : Results from N00C1 from the north central cancer treatment group

Tumor necrosis factor‐α (TNF‐α) is a putative mediator of the cancer anorexia/weight loss syndrome. The current study was designed to determine whether etanercept (a dimeric fusion protein consisting of the extracellular ligand‐binding portion of the human 75‐kilodalton TNF receptor linked to the Fc portion of human immunoglobulin [Ig] G1) could palliate this syndrome.

Search for Evidence-Based Approaches for the Prevention and Palliation of Hand–Foot Skin Reaction (HFSR) Caused by the Multikinase Inhibitors (MKIs)

BACKGROUND The anticancer multikinase inhibitors (MKIs) are associated with cutaneous adverse events, including hand-foot skin reaction (HFSR), a condition affecting 20%-40% of patients. Symptoms are usually mild, but can evolve into a painful condition that limits function and impacts quality of life (QoL), resulting in shortened cancer treatment duration or intensity. The goal of this study was to systematically review the literature on the prevention and palliation of MKI-associated HFSR, to identify areas for further clinical study, and to provide a foundation for evidence-based guidelines for HFSR management. METHODS Systematic searches of the National Library of Medicines PubMed database, Cochrane Reviews, BIOSIS, CancerLit, and the American Society of Clinical Oncology website were conducted using search terms for cutaneous toxicities associated with chemotherapeutic agents. Articles were categorized (C) based on type of agent and cutaneous reaction as: C1 (MKI and HFSR); C2 (MKI and other cutaneous toxicity); C3 (other antineoplastic agents and HFSR); and C4, other. RESULTS Of the 2,069 abstracts screened, 350 (17%) met the criteria for C1-C4, with 56 (16%) coded as C1 with details of HFSR histology, pathogenesis, clinical outcome, QoL impact, and/or prevention and treatment approaches in MKI-treated patients. No randomized, controlled trials (RCTs) on prevention/palliation of HFSR were identified. Anecdotal evidence or expert opinion advocated protective measures, preventive and therapeutic skin care, systemic analgesics for pain, vitamin B(6), and MKI dose modification. CONCLUSION No articles containing evidence from RCTs on preventive/palliative approaches to MKI-associated HFSR have been published. Systematic study of optimal treatment strategies for HFSR is needed to advance development of evidence-based treatment guidelines.

Motivational readiness for physical activity and quality of life in long-term lung cancer survivors

Little is known about the relationship between motivational readiness for physical activity and quality of life (QOL) in long-term lung cancer survivors. Long-term survivors are considered those who are living 5 years or more following a cancer diagnosis. This project examined the relationship between a self-report measure of motivational readiness for physical activity and QOL in a sample of 272 long-term lung cancer survivors. Participants (54% male, average age 70 years old) completed the mailed survey an average of 6 years after being diagnosed with lung cancer. Survey measures included the stage of change for physical activity and a set of single item QOL and symptom scales. Thirty-seven percent of respondents reported they currently engaged in regular physical activity (a total of 30 min or more per day, at least 5 days per week). Kruskal-Wallis tests revealed that those who reported engaging in regular physical activity reported a better overall QOL, better QOL on all five domains of QOL functioning (mental, physical, social, emotional, and spiritual), and fewer symptoms compared to those with a sedentary lifestyle. Physical activity level may have important QOL and symptom management benefits for long-term lung cancer survivors.