Drug Shortages in Oncology: ASCO Clinical Guidance for Alternative Treatments.

PURPOSE: To increase awareness, outline strategies, and offer clinical guidance on navigating the complexities of treatment planning amid antineoplastic drug shortages. METHODS: A multidisciplinary panel of oncologists, ethicists, and patient advocates was assembled to provide rapid clinical guidance to help providers navigate appropriate patient care in cases where rationing or alternative therapies must be considered. The groups of content experts developed general principles for resource allocation during shortages and clinical guidance on alternative therapies for specific disease sites. The recommendations are supported by evidence when available. RESULTS: A total of 44 volunteers with content expertise formed the Advisory Group that developed general guidance on the prioritization of antineoplastic agents in limited supply. Disease site-specific clinical guidance was then produced by subgroups on the basis of members' specialties and expertise. The majority of alternative treatment options were developed in consideration of cisplatin and carboplatin shortages. All guidance is posted on ASCO's website. RECOMMENDATIONS: The prioritization of antineoplastic agents in limited supply should be based on specific goals of the therapy where evidence-based medicine has shown survival outcome and life-extending benefit in both early and advanced stages. Recommendations for specific disease sites are presented. While management options vary according to the disease site, alternatives are presented. For settings in which there are no alternatives with comparable efficacy and safety, it is recommended that patients are referred to an area where the necessary drug is available or can be obtained.Additional information is available at asco.org/drug-shortages.

Treatment options after first-line immunotherapy in metastatic NSCLC.

Introduction: The recent approvals of checkpoint inhibitors as single agents or in combination with chemotherapy with programmed death ligand 1 expression of < or ≥1% have challenged clinicians when it is time to begin a metastatic lung cancer patient in second-line therapy. The advantages given by immunotherapy over conventional chemotherapy such as improved overall survival and a better toxicity profile make the second-line clinical scenario more difficult for a patient who faces a likely inferior regimen as well as toxicity which may significantly impact the quality of life.Areas covered: Options given today by the National Comprehensive Cancer Network are very limited, and essentially, we go back to conventional cytotoxic agents alone or in combination with biological agents if possible. In this article, we discuss the actual treatment available for this difficult scenario and some of the ongoing trials which aim to address this dilemma.Expert commentary: This is an unmet need in lung cancer management; we need a better understanding of the mechanism of resistance to immunotherapy so we can target them once the patient moves to second-line treatment.

Novel molecular targeted therapies for refractory thyroid cancer.

The incidence of thyroid cancer continues to increase and this neoplasia remains the most common endocrine malignancy. No effective systemic treatment currently exists for iodine-refractory differentiated or medullary thyroid carcinoma, but recent advances in the pathogenesis of these diseases have revealed key targets that are now being evaluated in the clinical setting. RET (rearranged during transfection)/PTC (papillary thyroid carcinoma) gene rearrangements, B-Raf gene mutations, and vascular endothelial growth factor receptor 2 (VEGFR-2) angiogenesis pathways are some of the known genetic alterations playing a crucial role in the development of thyroid cancer. Several novel agents have demonstrated promising responses. Of the treatments studied, multi-kinase inhibitors such as axitinib, sorafenib, motesanib, and XL-184 have shown to be the most effective by inducing clinical responses and stabilizing the disease process. Randomized clinical trials are currently evaluating these agents, results that may soon change the management of thyroid cancer.

Efficacy of sorafenib, a multi-tyrosine kinase inhibitor, in an adenoid cystic carcinoma metastatic to the lung: case report and review of literature.

INTRODUCTION: Treatment for squamous cell carcinoma of the head and neck has significantly improved with the addition of cetuximab, a monoclonal antibody against the epidermal growth factor receptor, to conventional cytotoxic agents. The most significant aspect of this treatment approach is the proof that head and neck cancers are suitable for targeted therapies as has been shown in other malignancies. Unfortunately, there are other rare histologic types of head and neck cancer such as adenocarcinoma and adenoid cystic carcinoma. The latter has traditionally been considered to be chemotherapy resistant and surgical resection with or without adjuvant radiation therapy has been the rule as far as treatment is concerned. The course of adenoid cystic carcinoma ranges from indolent to aggressive; however, most patients succumb to the disease as a result of distant metastases. This clinical scenario poses a challenge to oncologists. Several conventional chemotherapy regimens and novel targeted agents have been tried in this rare histologic subtype without success. CASE PRESENTATION: In this case report, we present a 59-year-old Caucasian female with refractory adenoid cystic carcinoma of the maxilla metastatic to the lung that responded to sorafenib, a novel multi-tyrosine kinase inhibitor, which targets angiogenesis, Raf kinase pathway, platelet-derived growth factor Ret, and c-Kit. CONCLUSION: This case illustrates the possibility that this chemoresistant tumor may need the inhibition or blocking of several oncogenic pathways. Certainly, it is imperative that more studies are done in this special population trying to identify tumorigenesis mechanisms that may be upregulated in this malignancy and could be potential targets for therapeutic development.

Hematopoietic cell transplantation in acute promyelocytic leukemia: a comprehensive review.

The past three decades have brought major therapeutic advances in the management of acute promyelocytic leukemia. The current state-of-the-art induction treatment with all-trans retinoic acid in combination with anthracycline-based chemotherapy results in long-lasting remissions and cure in up to 70% of newly diagnosed patients. Unfortunately, treatment failure still occurs in one-third of patients. When disease relapses, patients can achieve subsequent remissions with arsenic trioxide, all-trans retinoic acid with or without chemotherapy, or other therapies. Patients achieving molecular remissions after salvage therapy are generally considered candidates for high-dose chemotherapy and autologous hematopoietic cell transplantation as a postconsolidation strategy. On the other hand, patients with evidence of persistent hematologic or molecular disease after salvage therapy could be offered allogeneic hematopoietic transplantation if a suitable HLA-donor is identified and the patient's overall performance and clinical condition are permissible. We hereby provide a comprehensive review and analysis of published clinical trials that evaluate the role of hematopoietic cell transplantation across different stages of acute promyelocytic leukemia.