No abstract

Fertility-related perceptions varied among survivors, but the majority never underwent fertility testing. Uncertainty or concerns differed by current circumstances (e.g., wanting children and relationship status). Providers should routinely discuss potential infertility and offer testing throughout survivorship. A negative impact on romantic relationships may seem small, but should be considered for survivors who desire children and may discover they are infertile in the future.

Purpose This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl –tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. Methods Patients received mifamurtide 2 mg/m2 intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24 hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. Results The study began therapy in January 2008; the last patient completed therapy in October 2012. 205 patients were enrolled; median age was 16.5 years and 143/204 (72%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30 minutes post-infusion, then in a loglinear manner 2–6 hours post-dose; t1/2 was 2 hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2 mg/m2 mifamurtide across the age range. Patients reported 3,415 IRAE after 7,122 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills+fever or headache+fatigue symptom clusters. One and two year OS was 70.6% and 41.4%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N=40) had similar 2-year OS (38.8%) as the entire cohort (41.4%) Conclusions Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 41.4%. A randomized clinical trial would be required to definitively determine impact on patient outcomes.

Over the last 30 years, it has become apparent that oncology patients ages 15 to 39 have not reaped the same rewards of improved survival that we have seen in younger and older patients. As a result, in 2006 the Adolescent and Young Adult (AYA) Oncology Progress Review Group convened and examined the factors that impact the care of the 70,000 new cases per year (approximately 7% of all new cases) in the United States and published their findings. The reasons for inferior survival gains are of course multiple and include the settings in which patients are cared for, clinical trial enrollment, insurance coverage, varied treatment of sarcomas, varied treatment of acute lymphoblastic leukemia, the psychosocial impact of cancer and cancer survivorship. A new area of a yet-to-be completely defined subspecialty was born out of this meeting: AYA oncology. As a medical community we realized that these patients do not fit neatly into the pediatric nor adult world and, therefore, require a unique approach which many individuals, oncology centers, advocacy groups, and cooperative trial groups have started to address. This group of dedicated providers and advocates has made strides but there is still much work to be done on the local, national, and international level to make up for shortcomings in the medical system and improve outcomes. We review key components of AYA cancer care in 2015 that all providers should be aware of, how far we have come, where this movement is headed, and the obstacles that continue to stand in the way of better cure rates and quality of life after cure for this unique group of patients. Like an adolescent maturing into adulthood, this movement has learned from the past and is focused on moving into the future to achieve its goals.