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The use of intraperitoneal drug delivery in the treatment of malignant disease confined to the peritoneal cavity is based on the theoretical potential for increased exposure of the tumour to antineoplastic agents leading to improved cytotoxicity. Phase I studies have explored the safety and pharmacokinetic advantage of the regional administration of several drugs, including cisplatin (10 times higher than systemic delivery) and paclitaxel (1000 times higher). Phase II trials of second-line intraperitoneal chemotherapy of ovarian cancer, generally with cisplatin, have shown the potential for patients to achieve surgically-documented complete responses. Randomised trials of second-line regional therapy in patients with ovarian cancer have yet to be conducted, although non-randomised single institution experience has suggested the potential for long-term disease-free survival with this strategy. By contrast, several well-planned randomised trials of first-line intraperitoneal chemotherapy of small-volume residual advanced ovarian cancer after primary surgical cytoreduction have reported a survival advantage with regional drug delivery. Although a rationale can be proposed for intraperitoneal antineoplastic drug delivery in non-ovarian malignant disease involving the peritoneal cavity, current data do not support the use of this strategy outside the confines of well-designed clinical trials.

The standard initial management of epithelial ovarian cancer consists of surgical staging, operative tumour debulking including total abdominal hysterectomy and bilateral salpingo-oophorectomy, and administration of six cycles of intravenous chemotherapy with carboplatin and paclitaxel. Extensive and largely retrospective experience has shown that optimum surgical debulking to leave residual tumour deposits that are less than 1 cm in size is associated with improved patient outcomes. However, 75% of patients present with advanced (stage III or IV) disease and, although more than 80% of these women benefit from first-line therapy, tumour recurrence occurs in almost all these patients at a median of 15 months from diagnosis. Second-line treatments can improve survival and quality of life but are not curative. Advances in screening and understanding of molecular pathogenesis of ovarian cancer and development of novel targeted therapies (eg, bevacizumab) and practical intraperitoneal techniques for drug delivery are most likely to improve patient outcomes.

Malnutrition is a significant factor in predicting cancer patients’ quality of life (QoL). We systematically reviewed the literature on the role of nutritional status in predicting QoL in cancer. We searched MEDLINE database using the terms “nutritional status” in combination with “quality of life” together with “cancer”. Human studies published in English, having nutritional status as one of the predictor variables, and QoL as one of the outcome measures were included. Of the 26 included studies, 6 investigated head and neck cancer, 8 gastrointestinal, 1 lung, 1 gynecologic and 10 heterogeneous cancers. 24 studies concluded that better nutritional status was associated with better QoL, 1 study showed that better nutritional status was associated with better QoL only in high-risk patients, while 1 study concluded that there was no association between nutritional status and QoL. Nutritional status is a strong predictor of QoL in cancer patients. We recommend that more providers implement the American Society of Parenteral and Enteral Nutrition (ASPEN) guidelines for oncology patients, which includes nutritional screening, nutritional assessment and intervention as appropriate. Correcting malnutrition may improve QoL in cancer patients, an important outcome of interest to cancer patients, their caregivers, and families.

For more than 20 years, the combination of a platinum agent and a taxane has served as the primary chemotherapy strategy for epithelial ovarian cancer. Alternative approaches employing these drugs (intraperitoneal drug delivery, neoadjuvant therapy) have favorably impacted outcomes in selected patient populations. Multiple single agent and combination therapy strategies have been delivered in the second-line (or later) setting with the goal to prolong survival and optimize quality-of-life. The anti-angiogenic agent bevacizumab has been shown to be clinically active when added to chemotherapy and delivered as a “maintenance” strategy in the front-line, platinum-sensitive recurrent and platinum-resistant settings. Several poly-(ADP-ribose) polymerase (PARP) inhibitors are currently utilized as single-agent “second-line” treatment options or in the maintenance setting. Recent clinical research efforts in ovarian cancer have focused on the potential role of checkpoint inhibitors used alone or in combination with PARP inhibitors or anti-angiogenic agents.

The therapeutic options available to treat a wide range of malignancies are rapidly increasing. At the same time, the population being treated is aging with more cardiovascular risk factors, comorbid conditions, and associated poor cardiac reserve. Both traditional chemotherapeutic agents (for example, anthracyclines) and newer therapies (for example, targeted tyrosine kinase inhibitors and immune checkpoint inhibitors) have demonstrated profound cardiovascular toxicities. It is important to understand the mechanisms of these toxicities to establish strategies for the prevention and management of complications-arrhythmias, heart failure, and even death. In the first of this two-part review series, we focus on what is known and hypothesized about the mechanisms of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.

Traditional chemotherapeutic agents and newer targeted therapies for cancer have the potential to cause cardiovascular toxicities. These toxicities can result in arrhythmias, heart failure, vascular toxicity, and even death. It is important for oncologists and cardiologists to understand the basic diagnostic and management strategies to employ when these toxicities occur. While anti-neoplastic therapy occasionally must be discontinued in this setting, it can often be maintained with caution and careful monitoring. In the second of this two-part review series, we focus on the management of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.

The fundamental goal of maintenance therapy of cancer is to extend a clinically meaningful survival endpoint (overall, symptom-free, progression-free) while at the same time not substantially interfering with a patient’s quality of life. Several phase 3 randomized trials in ovarian cancer involving different anti-neoplastics (e.g., paclitaxel, anti-angiogenic agents, olaparib) have revealed an improvement in progression-free survival with generally acceptable side effect profiles, and as a result represent in appropriately selected patients a rational therapeutic strategy.

Both pre-clinical studies and phase 1-2 clinical trials have provided strong support for the potential role of regional drug delivery in the management of epithelial ovarian cancer, a disease process whose major manifestations remain largely localized to the peritoneal cavity in the majority of individuals with this malignancy. The results of 3 phase 3 randomized trials have revealed the favorable impact of primary cisplatin-based intraperitoneal chemotherapy in women who initiate drug treatment with small-volume residual ovarian cancer following an attempt at optimal surgical cytoreduction. Concerns have been raised regarding the toxicity of regional treatment, particularly the side-effect profile associated with cisplatin. One rational approach to improving the tolerability of intraperitoneal chemotherapy is to substitute carboplatin for cisplatin. This review discusses the rationale for and data supporting regional treatment of epithelial ovarian cancer, and highlights the potential role for intraperitoneal carboplatin in this clinical setting.

Over recent decades, truly impressive progress has been made in the outcome associated with the pharmacological antineoplastic management of women with advanced ovarian cancer. Following initial surgery, the large majority of patients with this malignancy will receive a chemotherapy regimen that includes a platinum drug (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel). Currently, objective responses are observed in approximately 60–80% of patients treated in the front-line setting, with documented improvements in overall survival compared with prior non-platinum and taxane programmes. Unfortunately, despite the high response rate to initial chemotherapy, the majority of women with advanced disease will experience recurrence of the malignant process and be candidates for a variety of possible second-line therapeutic options. It is well recognized that ovarian cancer patients who are documented to experience an initial response to platinum-based chemotherapy but where the disease recurs approximately 6 or more months following the completion of primary therapy, may have another clinically meaningful response (both objective and subjective) to a second platinum-based strategy. However, an optimal management approach in this setting remains to be defined. Furthermore, the malignant cell populations in all ovarian cancer patients who experience an initial relapse of the disease process will eventually be resistant to the platinum agents. In this setting, multiple drugs have been shown to be biologically active. Again, an optimal strategy to be employed in the platinum-resistant setting has yet to be demonstrated through the conduct of evidence-based trials. Reasonable goals of therapy in women with recurrent or resistant ovarian cancer are to improve overall survival, reduce the severity (and delay the occurrence) of symptoms and optimize overall quality of life.

A recent objective study has demonstrated that the use of adjuvant platinum-based intraperitoneal chemotherapy in patients with small-volume residual advanced-stage ovarian cancer remains limited, despite the publication of several phase III trials demonstrating superior overall survival associated with this approach. Several factors might explain this far less than satisfactory state of affairs.