Jatoi, Aminah

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.

Abstract 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 Medicine’s 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 B6, 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.

Abstract Rash from epidermal growth factor receptor inhibitors is common and negatively impacts the quality of life of cancer patients. Published guidelines recommend holding cancer therapy if the rash is severe. Does this recommendation hinge solely on improving patients' quality of life, or does it also hinge on the prevention of a potentially fatal, cutaneous adverse event? In other words, do patients die from rashes from epidermal growth factor receptor inhibitors? To our knowledge, the latter question has never before been asked and answered in an evidence-based fashion. Therefore, we conducted a systematic review of the published, prospectively conducted clinical trial literature on epidermal growth factor receptor inhibitors. The primary aim was to determine whether rash-related death has ever been reported in such trials. Among 117 such trials, which included 8,998 cancer patients, the rate of rash development was >50%, as expected. However, there were no reported deaths from a rash. Although we cannot conclude that a rash-related death from this class of agents can never occur, this systematic review provides evidence-based guidance on how best to counsel cancer patients who develop a rash from an epidermal growth factor receptor inhibitor. It suggests that quality of life issues should remain at the forefront as cancer patients and health care providers make decisions about holding cancer therapy.

Purpose To determine prognostic factors and impact of adjuvant chemotherapy (CT) and radiotherapy (RT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Patients and Methods We performed a retrospective review 472 consecutive patients who underwent complete resection with negative margins (R0) for invasive carcinoma (T1-3N0-1M0) of the pancreas between 1975 and 2005 at the Mayo Clinic in Rochester, MN. Exclusion criteria included metastatic or unresectable disease at surgery, positive surgical margins, and indolent tumor types (islet cell tumors and mucinous cystadenocarcinoma). Median RT dose was 50.4 Gy in 28 fractions; 98% of RT patients also received concurrent fluorouracil-based CT. Results Six patients died within 30 days of surgery. For the 466 surviving patients, median follow-up was 32.4 months; median OS was 21.6 months. Median OS after adjuvant CT-RT was 25.2 versus 19.2 months after no adjuvant therapy (P = .001). Two-year OS was 50% versus 39%, and 5-year OS was 28% versus 17%. Adverse prognostic factors identified by univariate and multivariate analysis included positive lymph nodes (risk ratio [RR] = 1.3; P < .001), high histologic grade (RR = 1.2; P < .001), and no adjuvant therapy (RR = 1.3; P < .001). Tumor extension beyond the pancreas was an adverse prognostic factor by univariate analysis alone (P = .03). Patients receiving adjuvant therapy had more adverse prognostic factors than those not receiving adjuvant therapy (P = .001). Conclusion This study represents one of the largest, single-institution, retrospective reviews of adjuvant therapy in patients after R0 resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CT-RT.

Abstract Purpose. Previous studies have found that marriage is associated with longer survival and better quality of life among lung cancer patients. The present study used the Mayo Clinic Lung Cancer Cohort to re-examine this issue. Methods. In total, 5,898 non-small cell lung cancer (NSCLC) patients, who had available information on marital status and who had been enrolled in the Mayo Clinic Lung Cancer Cohort (MCLCC), were the focus of this study. Patients had extensive baseline and follow-up data on cancer stage, cancer treatment, and prognostic factors. All patients had been followed within the MCLCC with at least annual confirmation of vital status and patient-reported quality of life (the Lung Cancer Symptom Scale and the Linear Analogue Scales of Assessment). Results. The numbers of patients who were married, single, divorced, and widowed at the time of cancer diagnosis were 4,457 (76%), 265 (4%), 440 (7%), and 736 (12%), respectively. No statistically significant difference in survival was observed among these four groups, even after adjusting for a variety of prognostic factors, such as age, gender, and tumor stage. However, exploratory analyses suggested that widowed and divorced patients received less aggressive cancer therapy, and certain patient subgroups, such as stage IA widowed patients, had a shorter survival. Divorced patients reported greater financial concerns, and married and widowed patients reported greater spirituality and better social support. Conclusion. This study did not observe differences in survival or quality of life based on marital status at the time of diagnosis of NSCLC, but subgroup analyses appear to suggest findings worthy of further exploration.

Purpose To answer the question, “should elderly non–small-cell lung cancer patients be offered elderly-specific trials?” Patients and Methods The North Central Cancer Treatment Group (NCCTG) performed a pooled analysis of elderly patients who participated in elderly-specific trials (required age ≥ 65 years) and age-unspecified trials (required age ≥ 18 years). Between 1998 and 2000, all NCCTG non–small-cell lung cancer (NSCLC) patients with incurable cancer, age ≥ 65 years, and receiving first-line chemotherapy were included. A total of 118 elderly patients participated in elderly-specific trials, and 108, in age-unspecified trials. Demographics and outcomes were compared based on trial type. Results The median age of elderly patients in elderly-specific trials was greater: median (range): 73 years (65 to 87) and 70 years (65 to 85), respectively (P < .001), as was the percentage older than 80 years: 17% and 3%, respectively (P = .0008). Median survival times were 232 and 302 days, respectively (P = .08). After adjustment for baseline age, Eastern Cooperative Oncology Group performance score, cancer stage, and body mass index, this survival difference was not statistically significant (hazard ratio = 1.25; P = .16). Grade 3 or worse nonhematologic adverse event rates were greater in age-unspecified trials (81% v 57%, respectively; P < .001), as were grade 3 or worse hematologic events (68% v 10%, respectively; P < .001). Conclusion Elderly patients in NSCLC elderly-specific trials suffered lower rates of severe adverse events with no statistically significant differences in survival. It seems that elderly-specific trials are providing quality care and helping to define optimal cancer therapy in the elderly, particularly among the “oldest of the old.”