Cancer and the Immune System: The History and Background of Immunotherapy.

OBJECTIVE: This article will outline the link between the immune system and cancer, and provide a historical timeline of immunotherapy developmental milestones. DATA SOURCES: Published data and peer reviewed publications/manuscripts, and textbook chapters. CONCLUSION: Science has provided a greater understanding of the interactions between cancer and the human immune system. As this knowledge has grown, there has been significant progress in the development of clinically effective cancer immunotherapies. IMPLICATIONS FOR NURSING PRACTICE: Nurses' knowledge of the different types of immunity and the interaction of cancer cells with the immune system provides foundational knowledge for understanding cancer immunotherapy. Familiarity with the history of cancer immunotherapy will allow nurses to better comprehend why immunotherapy is now a pillar of cancer treatment that continues to develop. This knowledge will translate to better understanding and provision of care for patients receiving immunotherapy for the treatment of cancer.

Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.

PURPOSE: CDK4 is amplified in > 90% of well-differentiated (WDLS) and dedifferentiated liposarcomas (DDLS). The selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD0332991 inhibits growth and induces senescence in cell lines and xenografts. In a phase I trial of PD0332991, several patients with WDLS or DDLS experienced prolonged stable disease. We performed an open-label phase II study to determine the safety and efficacy of PD0332991 in patients with advanced WDLS/DDLS. PATIENTS AND METHODS: Patients age ≥ 18 years experiencing disease progression while receiving systemic therapy before enrollment received PD0332991 200 mg orally once per day for 14 consecutive days in 21-day cycles. All were required to have CDK4 amplification by fluorescence in situ hybridization and retinoblastoma protein (RB) expression by immunohistochemistry (≥ 1+). The primary end point was progression-free survival (PFS) at 12 weeks, with 12-week PFS of ≥ 40% considered promising and ≤ 20% not promising. If ≥ nine of 28 patients were progression free at 12 weeks, PD0332991 would be considered active. RESULTS: We screened 48 patients (44 of 48 had CDK4 amplification; 41 of 44 were RB positive). Of those, 30 were enrolled, and 29 were evaluable for the primary end point. Grade 3 to 4 events included anemia (17%), thrombocytopenia (30%), neutropenia (50%), and febrile neutropenia (3%). At 12 weeks, PFS was 66% (90% CI, 51% to 100%), significantly exceeding the primary end point. The median PFS was 18 weeks. There was one partial response. CONCLUSION: Treatment with the CDK4 inhibitor PD0332991 was associated with a favorable progression-free rate in patients with CDK4-amplified and RB-expressing WDLS/DDLS who had progressive disease despite systemic therapy.