Outpatient Management Following Intensive Induction or Salvage Chemotherapy for Acute Myeloid Leukemia

Adults with newly diagnosed or relapsed acute myeloid leukemia (AML) commonly receive intensive chemotherapy to achieve disease remission. In the United States and many other countries, it is standard practice that these patients remain hospitalized “preemptively” until blood count recovery, owing to the risk for overwhelming infections and bleeding during pancytopenia. This care policy requires hospitalization for an average of 3 to 4 weeks after completion of chemotherapy. However, highly effective oral prophylactic antimicrobials are now available, and transfusion support of outpatients has become routine in recent years. As a result, the care of patients with hematologic malignancies treated with intensive modalities is increasingly shifting from inpatient to outpatient settings. Benefits of this shift could include the reduced need for medical resources (eg, transfusions or intravenous antimicrobial therapy), improved quality of life (QOL), decreased rates of nosocomial infections, and lower costs. Increasing evidence indicates that select AML patients undergoing intensive remission induction or salvage chemotherapy can be discharged early after completion of chemotherapy and followed closely in a well-equipped outpatient facility in a safe and cost-effective manner. Further demonstration that the current approach of preemptive hospitalization is medically unjustified, economically more burdensome, and adversely affects health-related QOL would very likely change the management of these patients throughout this country and elsewhere, resulting in the establishment of a new standard practice that improves cancer care.

Risk Stratification in Multiple Myeloma, Part 1: Characterization of High-Risk Disease

Survival in multiple myeloma (MM) is variable, ranging from several months to more than 15 years. While survival has recently improved with the use of novel therapy, approximately 25% of patients have a median survival of 2 years or less. Accurate identification of high-risk patients, and risk stratification, are crucial in improving outcomes for all patients. In the first part of this two part series, we review the currently identified prognostic factors characterized by disease burden (Durie-Salmon staging system, International Staging System, magnetic resonance imaging, (18F) fluorodeoxyglucose positron emission tomography, presence of extramedullary disease or plasma-cell leukemia), host factors (age, performance status, and renal function), tumor biology (proliferation rate, conventional cytogenetics, interphase fluorescence in situ hybridization, and gene expression profiling), and depth of response to therapy. Efforts have been made to identify ultra–high-risk patients by combining all the identified variables into a unifying comprehensive model. In the second part of this series, we will discuss the significance of these factors in the context of currently available therapies for MM, distinguishing between treatments that only improve outcomes of high-risk patients when compared with previous therapies, versus those that overcome high-risk status, thereby reclassifying these patients as standard risk.

Breast Cancer and Racial Disparity Between Caucasian and African American Women, Part 1 (BRCA-1)

Breast cancer is a commonly diagnosed malignancy and the second leading cause of cancer-related death among American women today. Despite the lower incidence of breast cancer among African American women, they are more likely to die from the disease each year than their white counterparts. We present a retrospective cohort study of the tumor registry data from electronic medical records of patients diagnosed with breast cancer at the University of Florida Health, Jacksonville from 2000 to 2005. A total of 907 patients were diagnosed with breast cancer; 445 patients with invasive breast cancer had complete medical records and were selected for this review. Much like previously published research, we found that African American patients presented with a more advanced stage and aggressive subtype of breast cancer than white patients, and were less likely to have health insurance. However, we have yet to determine if universal health care insurance can lead to improved health care access, better breast cancer awareness, and an enhanced attitude toward breast cancer screenings. Such factors would ultimately lead to an earlier diagnosis and better outcomes in both African American and white patients. We plan to investigate this critical issue in a follow-up study (BRCA-2; Breast Cancer and Racial Disparity Between Caucasian and African American Women, Part 2), which will begin a few years after the complete implementation of the universal health care law enacted by President Obama in 2010. The higher frequency of aggressive tumor subtypes in African American women warrants more attention. We suggest further research to determine whether decreasing the initial age for screening or increasing the frequency of mammograms in African American women would improve breast cancer outomes. This study underscores the importance of identifying and preventing obstacles in routine breast cancer screening, as well as increasing breast cancer awareness.

The “Hit Hard and Hit Early” Approach to the Treatment of Chronic Myeloid Leukemia: Implications of the Updated National Comprehensive Cancer Network Clinical Practice Guidelines for Routine Practice

In July 2012, the National Comprehensive Cancer Network (NCCN) updated its clinical practice guidelines in chronic myeloid leukemia (CML) with perhaps the most sweeping changes in a decade. These changes are expected to affect routine practice in CML, particularly with respect to criteria for early molecular response at 3 months and minimum specifications for molecular monitoring assays. Viewed as a whole, these updates signal an important shift in the recommendations for managing patients with CML. These updates support the wider use of standardized molecular monitoring assays, which should improve data consistency, reliability, and reproducibility. They also implicitly recommend that treating physicians strive for deeper levels of response early in the treatment course, in recognition of the effectiveness of current standard therapy. Most importantly, these updates reinforce the increasingly common perception that CML in its early chronic phase can be managed as a chronic disease in the majority of newly diagnosed patients. In this review, we outline the major updates to the guidelines, discuss the rationale behind these updates, and provide our perspectives on how they affect patient management in CML, including a preference for the use of newer tyrosine kinase inhibitors in the first-line setting.

Optimal Use of Iron Chelators in Pediatric Patients

Regular red cell transfusion therapy is used in the treatment of children with various hematologic disorders. These transfusions cause progressive iron loading, which if untreated results in endocrinopathies, cardiac arrhythmias, congestive heart failure, hepatic fibrosis, and premature death. Iron chelation therapy is used to prevent iron loading, remove excess accumulated iron, and detoxify iron. Three chelators have received US Food and Drug Administration approval: deferoxamine, deferasirox, and deferiprone, although deferiprone is approved only as a second-line agent. These chelators differ in their modes of administration, ability to remove iron from different organs, and adverse effect profiles. Chelation therapy should be individualized, taking into account the child’s and family’s preferences, adherence, adverse effects, ongoing transfusional iron intake, and the degree of cardiac and hepatic iron loading.

Managing Breast Cancer in the Older Patient

Breast cancer is a disease that is associated with aging, with almost one-half of all new breast cancer cases diagnosed annually in the United States occurring in women ages 65 and older. Recent data suggest that although breast cancer outcomes in younger women have shown substantial improvement as a result of advances in treatment and screening, the benefits in older women have been less pronounced. Although older patients have been underrepresented in cancer clinical trials, there is an emerging body of literature to help guide treatment decisions. For early-stage breast cancer, the discussion regarding treatment options involves balancing the reduction in risk of recurrence gained by specific therapies with the potential for increased treatment-related toxicity, potentially exacerbated by physiological decline or comorbidities that often co-exist in the older population. A key component of care is the recognition that chronologic age alone cannot guide the management of an older patient with breast cancer. Rather, treatment decisions must also take into account a patient’s functional status, estimated life expectancy, the risks and benefits of the therapy, potential barriers to treatment, and patient preference. This article reviews the available evidence for therapeutic management of early-stage breast cancer in older patients, and highlights data from the geriatric oncology literature that provide a basis on which to facilitate evidence-based treatment.

Association Between Cancer Types, Cancer Treatments, and Venous Thromboembolism in Medical Oncology Patients

Nearly 20% of all venous thromboembolism (VTE) occurs in cancer patients, and as many as 78% of cancer patients who develop a thrombotic event do so as outpatients. The risk of VTE in cancer patients is influenced by the type of cancer, its stage and histology, the presence of thrombophilia, and the many therapeutic interventions they receive (eg, surgery, chemotherapy, radiotherapy, supportive care). The greatest VTE risk appears to occur early after cancer diagnosis and in patients with late- or metastatic-stage malignancy. VTE most often occurs in cancers of the pancreas, ovary, kidney, lung, stomach, and brain, as well as in hematologic malignancies such as lymphoma and myeloma. The clinical consequences of thrombosis in cancer patients are typically more severe and more costly than events in patients without cancer. Patient-, cancer-, and treatment-related factors should be considered when assessing individual patients for their risk of VTE. Primary pharmacologic VTE prophylaxis should be given to all hospitalized medical and surgical oncology patients at risk, and this therapy should be considered for high-risk ambulatory outpatients (eg, myeloma patients receiving highly thrombogenic chemotherapeutic regimens, very-high-risk solid tumor patients with Khorana scores ≥3) who have no contraindications to anticoagulants.

Efficacy of Bisphosphonates and Other Bone-Targeted Agents in Metastatic Bone Disease From Solid Tumors Other Than Breast and Prostate Cancers

Metastatic bone disease complicates the course of malignancy in a substantial proportion of patients with advanced cancer. Bisphosphonates are now widely used to improve skeleton-related outcomes of patients with metastatic cancer to the bone. Most studies evaluating the efficacy of bisphosphonates and other bone-targeted agents have been performed in patients with metastatic breast and prostate cancer. Only a few studies have evaluated the role of bisphosphonates in other tumor types involving the skeletal system. We present a review of the clinical literature focusing on the current and potential roles of bisphosphonates (particularly zoledronic acid) and newer bone-targeted therapies in patients with metastasis to bone arising from solid tumors other than breast and prostate cancer.

Efficacy of Neoadjuvant Cisplatin and Oral Capecitabine in Triple-Negative Breast Cancers: A Pilot Study

Due to the lack of molecular targets, triple-negative breast cancers (TNBCs) typically represent a worse prognosis compared to their hormone-positive counterparts. While neoadjuvant chemotherapy has been used for breast cancers for a long time, there is no standard chemotherapy regimen for TNBCs. Cisplatin has generally been regarded as an effective chemotherapy agent against TNBCs. However, here we present a pilot study involving the use of cisplatin in combination with oral capecitabine in the neoadjuvant setting in 16 patients with TNBC. Twelve patients were African American and 4 patients were white. Six patients completed all 4 cycles of chemotherapy, 6 patients completed 3 cycles, and 4 patients completed 2 cycles. A complete clinical response was observed in 2 patients, and 10 patients achieved partial clinical response. One patient had progressive disease, and 3 patients were lost to follow-up or taken off study. Following chemotherapy, 12 patients underwent surgery (7 patients had breast conservation, and 5 patients had a mastectomy). Ten of the 12 patients who had surgery achieved a partial pathologic response and the other 2 patients had complete pathologic response. Grade 3 nausea, vomiting, and diarrhea occurred in 7 patients; 1 patient experienced dehydration and renal failure; and 5 patients had grade 1/2 hand-foot syndrome. There were no grade 4 or 5 toxicities. The response to cisplatin-capecitabine combination chemotherapy in the neoadjuvant setting was suboptimal compared to that with single-agent cisplatin in prior studies. The toxicity profile with this combination was also worse than that of cisplatin alone. Based on our findings, we do not recommend this combination regimen in the neoadjuvant setting for TNBCs. However, future studies analyzing the use of cisplatin with other combinations are warranted.

Ocular Adnexal MALTomas: Case Series of Patients Treated With Primary Radiation

Background: Ocular adnexal mucosal-associated lymphoid tissue lymphomas (MALTomas) are rare, and there are no phase III trials to guide treatment. Primary radiation therapy has been the typical management. This retrospective series reports the experience of a single institution and adds to the current literature. Methods: Our electronic medical record system and available paper charts were used to identify patients with MALTomas of the lacrimal gland or sac, conjunctiva, and orbital structures, including extraocular muscles. In order to determine pathology, staging, treatment information, local and distant control, salvage treatments, and late toxicity, records were reviewed. Results: Sixteen patients with ocular adnexal MALTomas had local radiation between 1992 and 2011 for primary or recurrent disease. Fifty percent of patients had lymphoma in the conjunctiva, 25% had lymphoma in the lacrimal sac/gland, and 25% of patients had lymphoma in the posterior orbit. Stage IAE disease occurred in 75% of patients, 6% had stage IIAE disease, and 19% of patients had a positive bone marrow biopsy. One patient received chemotherapy as part of initial therapy. The median radiation dose was 30 Gy (25.5–36 Gy) delivered with electrons (31%) or photons (69%). After a mean follow-up of 62.8 months, 2 patients had residual/progressive disease, 2 had contralateral recurrence, and 1 patient had a distant failure, for local control of 87.5% and overall disease control of 68.75%. Recurrence/progression occurred at a median of 35.45 months. Two patients with residual/progressive disease and 1 patient with a contralateral recurrence were followed, successfully salvaged, and have no evidence of disease. Fourteen patients are still alive, and there were no disease-related/toxicity deaths. Seven patients developed cataracts in the treated eye, 2 patients had radiation retinopathy, 2 had permanent dry eye syndrome, and 1 patient had severe keratopathy requiring enucleation. Six patients (3.75%) had worsening visual acuity of unclear etiology. Conclusions: Primary radiation therapy for ocular adnexal MALTomas with a median dose of 30 Gy led to excellent local control. Patients who did recur were successfully salvaged. Radiation was generally well tolerated, with expected cataractogenesis, given the dose required to achieve local control (with only 1 patient developing severe keratopathy after receiving the highest dose in this series).

Role of mTOR Inhibition in Preventing Resistance and Restoring Sensitivity to Hormone-Targeted and HER2-Targeted Therapies in Breast Cancer

Even with hormone-targeted and human epidermal growth factor receptor 2 (HER2)–targeted anticancer agents, intrinsic resistance or acquired resistance are common occurrences in estrogen receptor–positive and HER2-positive breast cancers, respectively. Potential mechanisms for resistance to targeted agents include steric inhibition imposed by other cellular elements, molecular changes in the target receptor, alterations in the regulation of downstream signaling components, compensatory cross-talk with other signaling pathways, and pharmacogenetic alterations in the host. Evidence suggests that both hormone receptor–positive tumors and HER2-overexpressing tumors use the phosphoinositide 3-kinase/Akt/ mammalian target of rapamycin (mTOR) pathway to escape control of antihormone and anti-HER2 therapies. The combination of mTOR inhibitors with hormone-targeted or HER2-targeted therapies appears to be a promising strategy for overcoming resistant disease and preventing the development of resistance.

Targeting Bone Physiology for the Treatment of Metastatic Prostate Cancer

Metastatic prostate cancer has a unique predilection for bone that can lead to significant clinical sequelae, such as fracture and cord compression. This tropism for bone yields not only clinical challenges, but also opportunities to understand the tumor biology in bone and to develop relevant therapeutic strategies. The process by which tumor cells migrate to bone, remain dormant, and then colonize and expand is based on complex interactions between prostate cancer tumor cells and the host microenvironment. This review will provide an overview of these interactions as well as therapies targeting osseous metastases in castration-resistant prostate cancer.

Sequential Treatment Strategies and Combination Therapy Regimens in Metastatic Renal Cell Carcinoma

Molecularly-targeted therapies have revolutionized the treatment of metastatic renal cell carcinoma (mRCC), but unmet needs remain. Efficacy of targeted agents is transient, and questions regarding optimal sequencing of therapies and benefits versus risks of combination therapy remain largely unanswered. In this article, an overview of ongoing/recently completed clinical trials evaluating sequential treatment strategies and combination therapy regimens is presented, along with a brief discussion of predictive biomarkers and prognostic factors. Several ongoing/recently completed clinical studies have been designed to help address 2 major questions currently facing physicians treating patients with mRCC: 1) What is the optimal sequence of targeted agents? and 2) Does combination therapy with targeted agents benefit patients with mRCC? Results of these trials may help establish the degree to which cross-resistance between agents occurs and which agents, when used consecutively, are associated with the most favorable outcomes. Clinical trial data maturing in the next 1–2 years should provide insight into the most effective treatment sequences and the benefits versus risks of combination therapies. Whether results of these studies will lead to a paradigm shift in treatment recommendations for patients with mRCC remains to be determined.

SHARE: A French Multicenter Phase III Trial Comparing Accelerated Partial Irradiation Versus Standard or Hypofractionated Whole Breast Irradiation in Breast Cancer Patients at Low Risk of Local Recurrence

The standard treatment for breast cancer patients at low risk of recurrence is based on conservative surgery followed by radiation therapy delivered to the whole breast. The accelerated partial breast irradiation (APBI) concept, developed more than 15 years ago, could be an option in selected patients. However, the ideal patient profile for APBI is still not clearly identified. Recent reports from the American Society for Radiation Oncology (ASTRO) and the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) have suggested selection criteria for “suitable patients” who could receive APBI outside of clinical trials. Currently, there are 6 ongoing phase III trials. All are characterized by a significant heterogeneity regarding inclusion criteria and stratification factors. The French UNICANCER trial (SHARE; ClinicalTrials.gov identifier NCT01247233) will randomize 2,800 patients in 3 arms: APBI (1 week) using 3-dimensional (3D) conformal radiotherapy, standard radiotherapy (6.5 weeks), and hypofractionated radiotherapy (3 weeks). In this article, we review the reported retrospective studies as well as older randomized trials. We will also describe the differences between the 6 ongoing phase III trials and the particularities of the French SHARE trial.

Advances in the Management of Muscle-Invasive Bladder Cancer Through Risk Prediction, Risk Communication, and Novel Treatment Approaches

Although level I evidence supports the use of neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy for the management of patients with muscle-invasive bladder cancer (MIBC), these treatment modalities are utilized in only a subset of patients. The reasons for lack of implementation of these treatment standards are multiple; patients may be considered ineligible for cisplatin or too old for safe cystectomy. Better means of determining a patient’s probability of recurrence with surgery alone, or likelihood of benefit with neoadjuvant chemotherapy, are clearly needed. Models have been developed to individualize estimates of non–organ-confined disease based on pretreatment variables. It is critical that clinicians are able to effectively communicate complex risk-related data to patients to facilitate a shared medical decision.

Management of Biochemically Recurrent Prostate Cancer After Local Therapy: Evolving Standards of Care and New Directions

Abstract: Among men treated with prostatectomy or radiation therapy for localized prostate cancer, the state of an increasing prostate-specific antigen (PSA) level is known as biochemical recurrence (BCR). BCR can be predictive of the development of subsequent distant metastases and ultimately death, but BCR often predates other signs of clinical progression by several years. Although patients may be concerned about their rising PSA levels, physicians attempting to address patient anxiety must inform them that BCR is not typically associated with imminent death from disease, and that the natural history of biochemical progression may be prolonged. Misinterpretation of the significance of early changes in PSA may cause patients to receive androgen deprivation therapy (ADT) prematurely, especially in settings where the disease is unlikely to impact survival. In addition, knowledge of the morbidities associated with ADT (hot flashes, impotence, sarcopenia, metabolic syndrome, bone loss, and increased risk of vascular disease) has accelerated the search for alternative treatment options for these patients. Clinical trials investigating when and how to best use and supplement hormonal therapies in this patient population are under way, as are trials of novel nonhormonal targeted agents, immunotherapies, natural products, and other pharmaceuticals that have been approved by the US Food and Drug Administration (FDA) for other indications. This review will summarize the acceptable standards of care for the management of biochemically recurrent prostate cancer, and will also outline some novel experimental approaches for the treatment of this disease state.

Advances in the Management of Biliary Tract Cancers

Abstract: Biliary tract cancers, although uncommon, are highly fatal malignancies. Current treatments fail to cure or control the majority of tumors. Given the complexity of the anatomy and the often aggressive nature of the disease, multidisciplinary treatment, including palliation, is often required. However, systemic therapy with cytotoxics and/or targeted agents is routinely the mainstay of treatment for patients with advanced biliary tract cancers, and new targets and agents provide hope for this disease. This article focuses on recent advances in the management of biliary tract cancers, with a special focus on the molecular basis for current therapeutic investigation in this disease.

Personalized Care in Uterine Cancer

Abstract: Endometrial cancer typically presents at an early stage when surgery alone, with or without radiotherapy, is often curative. However, in women who present with advanced disease or who develop disease recurrence, long-term prognosis is poor. While surgical cytoreduction remains the mainstay of initial therapy, over the last several decades, the roles of cytotoxic chemotherapy, radiotherapy, and hormonal therapy have been evaluated in both the adjuvant and recurrent setting in an attempt to improve long-term survival while also minimizing associated toxicities. Unfortunately, response rates remain poor and survival is limited in these settings. More recently, with the introduction of personalized cancer treatment, several biologic agents have been developed that target specific pathways critical to tumor initiation and growth. Molecular studies have found that many endometrial cancers are driven by some of these tumorigenic pathways, which has led to early clinical studies evaluating the role of these targeted agents in patients with advanced or recurrent endometrial cancer. This review describes existing treatment options for patients with early and advanced endometrioid endometrial cancer, as well as for patients with uterine serous cancers. Furthermore, this review examines the growing body of literature involving targeted biologic agents as treatment for patients with advanced or recurrent endometrial cancer.

The Tumor Microenvironment in Follicular Lymphoma

Abstract: Like other B-cell lymphomas, the development and progression of follicular lymphoma (FL) involves complex interactions between the neoplastic B cells and the surrounding microenvironment. Malignant B cells can manipulate the microenvironment by skewing the differentiation of immune cells, attracting regulatory T cells or suppressive monocytes, or secreting cytokines that promote an immunosuppressive environment. The importance of the microenvironment in FL has been demonstrated using methodologies such as gene expression profiling, which has shown that the nature of the tumor microenvironment predicts survival in patients with FL and may influence the response to immunotherapy and risk of transformation. Strategies that both enhance an effective antitumor response and reverse immunosuppression and dysfunction will be essential in the development of effective immunotherapeutic approaches in this disease.

Current Controversies in the Management of Biochemical Failure in Prostate Cancer

Abstract: Approximately 35% of prostate cancer patients will experience a biochemical recurrence within 10 years of receiving treatment. Among patients who develop biochemical recurrence, approximately one-third will develop radiographic evidence of metastatic disease within 8 years from the time of prostate-specific antigen (PSA) elevation. Development of biochemical recurrence with a rising PSA level causes significant anxiety for both the patient and his treating oncologist. There is no consensus regarding the PSA level that indicates disease recurrence after radical prostatectomy. Androgen-deprivation therapy (ADT) is the standard of care for these patients. The key components that influence the consideration of ADT are the rate of change of the PSA level (PSA doubling time), the patient’s anxiety regarding his PSA level, and the side effects associated with ADT. One of the most prominent controversies in the treatment of biochemical recurrence is the timing of ADT (early vs late) for treatment of PSA recurrence. An emerging treatment option is continued active surveillance, especially in patients who are asymptomatic. Other management approaches under investigation include intermittent ADT, the combination of ADT and novel agents, and peripheral androgen blockade.