A review of cancer immunotherapy: from the past, to the present, to the future.

Compared with previous standards of care (including chemotherapy, radiotherapy, and surgery), cancer immunotherapy has brought significant improvements for patients in terms of survival and quality of life. Immunotherapy has now firmly established itself as a novel pillar of cancer care, from the metastatic stage to the adjuvant and neoadjuvant settings in numerous cancer types. In this review article, we highlight how the history of cancer immunotherapy paved the way for discoveries that are now part of the standard of care. We also highlight the current pitfalls and limitations of cancer checkpoint immunotherapy and how novel research in the fields of personalized cancer vaccines, autoimmunity, the microbiome, the tumour microenvironment, and metabolomics is aiming to solve those challenges.

Endocrine therapy for breast cancer in the primary care setting.

The treatment of hormone-positive breast cancer (bca) is a rapidly evolving field. Improvement in the understanding of the mechanisms of action and resistance to anti-hormonal therapy has translated, in the past decade, into multiple practice-changing clinical trials, with the end result of increased survivorship for patients with all stages of hormone-positive cancer. The primary care physician will thus play an increasing role in the routine care, surveillance, and treatment of issues associated with anti-hormonal therapy. The aim of the present review was to provide a focused description of the issues relevant to primary care, while briefly highlighting recent advances in the field of anti-hormonal therapy. Key Points: ■ Hormone-positive bca is the most prevalent form of bca and, compared with the other subtypes, is usually associated with better survival.■ Survivorship has significantly increased for all stages of hormone-positive bca, making the primary care physician a key player in the care of affected patients.■ The two most common classes of anti-hormonal agents used in these patients are selective estrogen receptor modulators and aromatase inhibitors. Each class of medication is associated with signature side effects.■ Within the past decade, multiple novel estrogen receptor blockers (for example, fulvestrant) and agents aimed at circumventing resistance to endocrine therapy [inhibitors of cyclin-dependent kinase 4/6 and of mtor (the mechanistic target of rapamycin)] have gained clinical ground. Understanding their side effects will be increasingly relevant to primary care physicians.■ Multidisciplinary care is always encouraged in the care of cancer patients receiving anti-hormonal therapy.

The trastuzumab and vinorelbine combination: an alternative to taxane-based chemotherapy for early-stage and locally advanced her2-positive breast cancer.

BACKGROUND: Anthracyclines and taxanes have historically constituted the backbone of chemotherapy regimens for patients with breast cancer positive for the human epidermal growth factor receptor 2 (her2). For a subset of patients who categorically refuse alopecia, or for those with a contraindication to those drugs, there is an urgent need to define alternative regimens. Here, we report our institutional experience with trastuzumab and vinorelbine (tv), a combination with good clinical activity and a good side effect profile for patients with her2-positive breast cancer. METHODS: In a retrospective analysis, outcomes data were extracted for patients receiving tv as their only chemotherapy in the non-metastatic setting at the Jewish General Hospital. For the most part, tv was administered weekly for 6 months, followed by trastuzumab for 6 months. RESULTS: The analysis identified 46 patients (mean age: 64 years) who received tv between 2003 and 2012 (n = 36 adjuvant, n = 10 neoadjuvant). Of the patients in the adjuvant group, 81% had stage i disease. In the neoadjuvant group, 3 patients experienced a complete pathologic response. Only 1 patient experienced local recurrence after a short course (3 months) of adjuvant tv. Overall survival and breast cancer-specific survival were 94% and 98% respectively at a median 5 years of follow-up. Febrile neutropenia-induced sepsis resulted in the death of 1 patient with significant medical comorbidities; 2 other patients died of comorbidities unrelated to their cancer or treatment. Grades 3 or 4 adverse events included neutropenia (23%), febrile neutropenia (10%), fatigue (2%), and anemia (2%). CONCLUSIONS: For patients with non-metastatic breast cancer refusing alopecia, or for patients who are not candidates for standard chemotherapy, tv is a reasonable alternative to standard adjuvant chemotherapy.

Acute liver failure because of chronic lymphocytic leukemia: case report and review of the literature.

Infiltration of the liver by hematologic malignancies is an uncommon cause of liver failure. B-Cell chronic lymphocytic leukemia (cll) is a usually indolent disease that may infiltrate the liver, but based on a review of the literature, has never been reported to induce acute liver failure. Here, we describe the case of a 78-year-old woman with acute liver failure secondary to infiltration with cll being unresponsive to chemotherapy and causing death. This case is notable because of its atypical presentation and ultimate poor prognosis.

Potential cost-effectiveness of rifampin vs. isoniazid for latent tuberculosis: implications for future clinical trials.

SETTING: Standard treatment for latent tuberculosis infection (LTBI) is 9 months daily isoniazid (9INH). An alternative is 4 months daily rifampin (4RMP), associated with better completion and less toxicity; however, its efficacy remains uncertain. OBJECTIVES: To assess the cost-effectiveness of these regimens for treating LTBI in human immunodeficiency virus negative persons, using results from a recent clinical trial, plus different scenarios for 4RMP efficacy, and to estimate the costs of an adequately powered noninferiority trial and resulting savings from substitution with 4RMP. DESIGN: A decision-analysis model tracked TB contacts and lower-risk tuberculin reactors receiving 9INH, 4RMP or no treatment. For different 4RMP efficacy scenarios, we estimated the cost-effectiveness, sample size and cost of non-inferiority trials, and potential cost savings substituting 4RMP for 9INH for 10 years in Canada. RESULTS: With an assumed 4RMP efficacy of 60%, 9INH was more effective but slightly more expensive. Above a threshold efficacy of 69%, 4RMP was cheaper and more effective than 9INH. If the true efficacy of 4RMP is ≥75%, a trial powered to detect non-inferiority with a lower limit of 60% estimated efficacy (~20 000 subjects) may lead to cost savings within 10 years, even with the extreme assumption that Canada bears the entire cost. CONCLUSION: 4RMP may be a reasonable alternative to 9INH. Costs of a large-scale non-inferiority trial may be offset by subsequent savings.