Safe Handling of Hazardous Drugs: ASCO Standards.

PURPOSE: To provide 2019 ASCO standards on the safe handling of hazardous drugs. METHODS: An Expert Panel was formed, and a systematic review of the literature on closed system transfer devices was performed to May 2017 using PubMed. The Cochrane Database of Systematic Reviews, PubMed, and Google Scholar were used to search for studies of medical surveillance and external ventilation/health effects of exposure to vapors to November 2017. Available standards were considered for endorsement. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The search for primary research found no studies that addressed health outcomes as they relate to the identified interventions of interest. The ASCO Expert Panel endorses the best practices for safe handling of hazardous drugs as issued by the Occupational Safety and Health Administration, US Pharmacopeia Chapter 800, and Oncology Nursing Society with clarifications in four key areas: medical surveillance, closed system transfer devices, external ventilation of containment secondary engineering controls or containment segregated compounding areas, and alternative duties. CONCLUSION: The ASCO standards address the need for clear standards concerning safe handling of hazardous oncology drugs. More research is needed in several key areas to quantify the level of risk associated with handling hazardous drugs in current workplace settings where the hierarchy of controls is consistently applied. Additional information is available at www.asco.org/safe-handling-standards .

Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study.

PURPOSE: A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen. METHODS: GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1-5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate-no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR > 27 %. RESULTS: Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %). CONCLUSION: The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin. Trial registration Clinical trial information NCT01736917.

Observations of second primary malignancy in patients with multiple myeloma.

BACKGROUND: Advances in the treatment of multiple myeloma have resulted in immunomodulatory (IMiD) agents becoming integral to the standard treatment armamentarium. IMiD agents are effective in the initial and relapsed settings of multiple myeloma. Three studies evaluating the duration of remission in maintenance lenalidomide vs. placebo reported an increased incidence of second primary malignancies in patients receiving maintenance therapy. The purpose of this study was to evaluate the incidence of second primary malignancies after IMiD exposure for standard induction and relapsed therapy in myeloma. PATIENTS AND METHODS: A retrospective chart review was conducted at the Indiana University Simon Cancer Center in Indianapolis, Indiana. Patients were older than 18 years and had been diagnosed with multiple myeloma. Patients with a previous diagnosis of cancer were excluded. The primary objective was to assess the incidence of second primary malignancies in all patients. Secondary objectives included the type of malignancy, whether patients had been previously treated with IMiD therapy and the time from treatment initiation to diagnosis of a second malignancy. RESULTS: Three hundred twenty-five patients were reviewed and 279 were included in the study. Ten patients were diagnosed with a second primary malignancy (3.5%). Nine of the 10 patients were treated with IMiD therapy before diagnosis (P = .169). The mean time to diagnosis was 360 days for all patients. CONCLUSION: The incidence of second primary malignancy was not statistically significant in the IMiD-treated patients. Further long-term follow-up is needed to better assess the potential adverse events of these novel agents.

Prophylaxis with sirolimus and tacrolimus ± antithymocyte globulin reduces the risk of acute graft-versus-host disease without an overall survival benefit following allogeneic stem cell transplantation.

Methotrexate (MTX) is a standard agent used in combination with calcineurin inhibitors for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic cell (HCT) transplantation. We retrospectively compared the incidence of acute GVHD (aGVHD), transplant-related morbidity, and mortality in patients given sirolimus/tacrolimus ± antithymocyte globulin (ATG) versus MTX/tacrolimus or cyclosporine and allogeneic transplantation for hematologic malignancies. Between January 1, 2005, and April 30, 2009, 106 consecutive patients received peripheral blood HCT or bone marrow grafts after 1 of 6 myeloablative conditioning regimens. The incidence of grade II-IV aGVHD was 18.6% in patients who received sirolimus/tacrolimus compared to 48.9% who received MTX (P = .001). The incidence of grade III-IV aGVHD was 5% and 17% (P = .045), respectively. There was no difference in overall survival (OS) between the groups (P = .160). Chronic GVHD (cGVHD) occurred in 40.4% who received sirolimus and 41.9% receiving MTX (P = .89). The incidence of thrombotic microangiopathy or interstitial pneumonitis was not significantly different between groups. The reduction in the risk of severe aGVHD was offset by an increased (20% versus 4%, P = .015) incidence of and mortality from sinusoidal obstructive syndrome (SOS). Sirolimus/tacrolimus appears to reduce the incidence of aGVHD after conventional allotransplantion compared to MTX-calcineurin inhibitor prophylaxis; however, this did not improve survival.

Iron chelation therapy in myelodysplastic syndromes.

PURPOSE: To understand how to appropriately recognize and manage iron overload with iron chelation therapy (ICT) in patients with myelodysplastic syndromes (MDS), evaluation of the role of different agents available for management of iron overload, including efficacy, safety, and economic considerations for transfusion-dependent patients with MDS, is provided. SUMMARY: Patients with MDS have a high incidence of anemia, which often requires treatment. Supportive care measures such as red blood cell transfusions and erythroid colony stimulating factors are mainstays of therapy. Use of long-term transfusion therapy has limitations in patients with MDS due to the risk of developing iron overload. Strategies to manage iron overload include phlebotomy and ICT with agents such as deferoxamine and deferasirox. Data evaluating pharmacologic therapy for treatment of iron overload in patients with MDS suggest timely intervention can mitigate the morbidity associated with this clinical syndrome. CONCLUSION: Development of practical management strategies to implement and optimize ICT using deferoxamine and deferasirox will be important to provide optimal care for transfusion-dependent patients with MDS.

Novel treatment strategies for chronic myeloid leukemia.

PURPOSE: Despite dramatic advances in the treatment of chronic myeloid leukemia (CML), resistance to therapeutic agents has emerged as a significant treatment dilemma. Mutations of the BCR-ABL kinase domain, a common mechanism of resistance to imatinib in CML, are discussed. SUMMARY: Several new targeted kinase inhibitors have reached clinical trials and have proved to be efficacious in halting the oncogenic activity of most BCR-ABL mutants. Dasatinib is 300 times more potent than imatinib at BCR-ABL inhibition, has few side effects, and inhibits the SRC family kinases. Nilotinib inhibits BCR-ABL at 20-50 times more potency than imatinib. Both agents were highly effective in treating chronic phase CML but were less effective at treating accelerated phase CML in early phase clinical trials. In addition to these specific kinase inhibitors, farnesyl transferase inhibitors are actively being investigated. Vaccination strategies are undergoing clinical investigation transitioning from animal models to human clinical trials. CONCLUSION: The new kinase inhibitors, dasatinib and nilotinib, are emerging as plausible therapeutic options for the treatment of imatinib-refractory CML.