Cancer Journal 

About: Cancer Journal is an academic journal published by Wolters Kluwer Health. The journal publishes majorly in the area(s): Cancer & Radiation therapy. Over the lifetime, 2019 publications have been published receiving 57501 citations.

Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial.

Abstract: PURPOSE Zoledronic acid, a new and more potent bisphosphonate, was compared with pamidronate, the current standard treatment for patients with osteolytic or mixed bone metastases/lesions. PATIENTS AND METHODS A total of 1,648 patients with either Durie-Salmon stage III multiple myeloma or advanced breast cancer and at least one bone lesion were randomly assigned to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. The primary efficacy endpoint was the proportion of patients experiencing at least one skeletal-related event over 13 months. RESULTS The proportion of patients with at least one skeletal-related event was similar in all treatment groups. Median time to the first skeletal-related eventwas approximately 1 year in each treatment group. The skeletal morbidity rate was slightly lower in patients treated with zoledronic acid than in those treated with pamidronate, and zoledronic acid (4 mg) significantly decreased the incidence and event rate for radiation therapy to bone, both overall and in breast cancer patients receiving hormonal therapy. Pain scores decreased in all treatment groups in the presence of stable or decreased analgesic use. Zoledronic acid (4 mg) and pamidronate were equally well tolerated; the most common adverse events were bone pain, nausea, fatigue, and fever and < 5% of serious adverse events were related to the study drug. The incidence of renal impairment among patients treated with 4 mg of zoledronic acid via 15-minute infusion was similar to that among patients treated with pamidronate. CONCLUSIONS Zoledronic acid (4 mg) via 15-minute intravenous infusion was as effective and well tolerated as 90 mg of pamidronate in the treatment of osteolytic and mixed bone metastases/lesions in patients with advanced breast cancer or multiple myeloma. (Can-

Managing cytokine release syndrome associated with novel T cell-engaging therapies.

Abstract: Chimeric antigen receptor (CAR)-modified T cells and bispecific T cell-engaging antibodies have demonstrated dramatic clinical responses in recent clinical trials The hallmark of these novel highly active immunotherapies is nonphysiologic T cell activation, which has correlated not only with greatly increased efficacy but also with notable toxicity in some cases We and others have observed a cytokine release syndrome (CRS), which correlates with both toxicity and efficacy in patients receiving T cell-engaging therapies In addition to elevations in effector cytokines, such as interferon-γ, cytokines associated with hemophagocytic lymphohistiocytosis or macrophage activation syndrome, such as interleukin (IL)-10 and IL-6, may also be markedly elevated Whereas corticosteroids may control some of these toxicities, their potential to block T cell activation and abrogate clinical benefit is a concern Detailed studies of T cell proliferation and the resultant immune activation produced by these novel therapies have led to more targeted approaches that have the potential to provide superior toxicity control without compromising efficacy One approach we have developed targets IL-6, a prominent cytokine in CRS, using the IL-6R antagonist tocilizumab We will review the pathophysiology and management options for CRS associated with T cell-engaging therapies

Antibody-drug conjugates for cancer therapy.

Abstract: The antibody-drug conjugate (ADC) concept is to use an antibody to deliver a cytotoxic drug selectively to a target such as a tumor-associated antigen. Such conjugates represent a broadly applicable approach to enhance the antitumor activity of antibodies and improve the tumor-to-normal tissue selectivity of chemotherapy. Critical parameters for ADC development include target antigen selection, conjugate internalization by tumor cells, drug potency and stability of the linker between drug and antibody. Other important considerations include the conjugation methods, drug-to-antibody ratio, and the effects of drug conjugation on antibody properties. Highly potent drugs with more stable linkers have been attached to a new generation of antibodies to create conjugates with pronounced antitumor activities in preclinical studies and encouraging results in early stage clinical trials. This review details these advances, discusses some of the remaining challenges, and overviews ADCs currently in clinical trials for cancer therapy.

A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy.

Abstract: PURPOSE: Angiosarcoma is a rare vascular malignancy, and there are few published data to guide chemotherapy treatment decisions. We present a retrospective analysis of angiosarcoma encompassing all anatomic sites of disease presenting to a single institution over a 14-year period. Characteristics at presentation and prognostic factors are reviewed. For patients with unresectable disease, progression-free survival with various chemotherapy regimens is described. PATIENTS AND METHODS: Pathological confirmation of all cases was performed before they were included in this analysis. One hundred twenty-five patients with angiosarcoma were seen and treated between January 1, 1990 and December 31, 2003. RESULTS: Angiosarcoma showed marked variation by anatomic site regarding gender ratio, median age at diagnosis, overall survival, and response to chemotherapy. Overall 5-year survival was 31% for angiosarcoma. Superficial depth and negative microscopic surgical margins correlated with longer overall survival, but tumor size did not reach significance as a prognostic factor. For unresectable angiosarcoma, doxorubicin based regimens yielded progression-free survival of 3.7-5.4 months. Paclitaxel achieved a progression-free survival of 6.8 months for scalp angiosarcoma and 2.8 months for sites below the clavicle. DISCUSSION: Angiosarcoma is an aggressive malignancy characterized by biologic heterogeneity at different anatomic sites and relative sensitivity to paclitaxel and doxorubicin.

The Contribution of Angiogenesis to the Process of Metastasis.

Abstract: The role of angiogenesis in tumor growth has been studied continuously for over 45 years. It is now appreciated that angiogenesis is also essential for the dissemination and establishment of tumor metastases. In this review, we focus on the role of angiogenesis as a necessity for the escape of tumor cells into the bloodstream and for the establishment of metastatic colonies in secondary sites. We also discuss the role of tumor lymphangiogenesis as a means of dissemination of lymphatic metastases. Appropriate combination therapies may be used in the future to both prevent and treat metastatic disease through the rational use of antiangiogenic and antilymphangiogenic therapies in ways that are informed by the current and future work in the field.