Cancer Treatment Reviews

Editorial Board

2010-04-01

Management of prostate cancer recurrence after definitive radiation therapy

Christian Boukaram, Jean-Michel Hannoun-Levi — 2010-01-25

Summary: The management of prostate cancer (PC) recurrence after definitive radiation therapy (RT) is shifting and there is no consensus regarding the optimal strategy. The major challenge is determining the anatomical site of relapse. In case of biochemical relapse (BR), androgen deprivation therapy (ADT) is a non-curative option commonly used, while patients with a local PC recurrence could be managed through a curative intent. Based on a Pubmed data search, this manuscript focused on the management of post-RT local PC recurrences. In case of BR (nadir+2ng/ml), classical imaging work-up is not contributive for PSA levels <10ng/ml while new imaging investigations (diffusion MRI, 11C-choline PET) are more sensitive to detect local and distant recurrences at lower PSA levels. Positive prostate biopsies are the only method for confirming local recurrence, although this technique presents limitations. Primary PC presentation as well as PSA-related features (interval to failure, PSA kinetic) and patient features (life expectancy, urinary, sexual status) are important to consider. Results of curative salvage options (radical prostatectomy, cryotherapy, brachytherapy and high-intensity focused ultrasound-HIFU) are analyzed and discussed. Each of these therapies appears feasible and has its own set of experience and toxicity profile. Other therapeutic options (photodynamic therapy, ADT, observation) are discussed. Longer follow-up and mature series are needed to evaluate the optimal strategy and prospective trials are warranted. Each clinical situation should be discussed in a multidisciplinary setting. Different options should be explained to the patient and decision should be taken after balancing treatment outcomes with life expectancy.

Treatment of the pregnant mother with cancer: A systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part I: Solid tumors

Hatem A. Azim, Fedro A. Peccatori, Nicholas Pavlidis — 2009-12-16

Summary: The association of cancer and pregnancy is increasingly encountered nowadays in clinical practice. Due to the relative rarity of the situation, it lacks a systematized approach. Different systemic therapies are used in managing cancer with uncertainty regarding the potential hazards they could pose on the pregnancy and/or the fetus.We have performed a systematic review of literature to identify all reports addressing cancer patients who were exposed to any of the known systemic therapies during the course of the pregnancy. The results were discussed in two parts; part I addresses pregnant patients with solid tumors while part I for those with hematological malignancies.In part I, we identified different solid tumors diagnosed and treated during the course of pregnancy. Breast cancer was the most commonly treated followed by ovarian cancer. Other tumors were treated as well including lung cancer, cervical cancer, sarcoma and melanomas. It is important to acknowledge the intent of therapy (palliative vs. curative) and the patients has to be properly counseled to reach an informed decision.We aim to provide a more robust consensus on how to approach these cases and provide a higher degree of evidence to support the safety of applying certain management strategies over the other.

Treatment of the pregnant mother with cancer: A systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part II: Hematological tumors

Hatem A. Azim, Nicholas Pavlidis, Fedro A. Peccatori — 2009-12-17

Summary: Managing pregnant patients with hematological tumors pose even more conflicts compared to solid tumors. Unlike the majority of solid tumors, hematological malignancies are potentially curable; hence it is important to deliver the best treatment options available, which sometimes could be too aggressive to deliver during pregnancy.In part II, we report the results of women with hematological malignancies treated with systemic therapies during the course of pregnancy. Lymphoma, acute leukemia and chronic myeloid leukemia were the most commonly treated.We discuss the safety of the different regimens reported and propose alternatives to standardized approaches in case they pose significant risk to the pregnancy and/or the fetus.

Targeted therapeutic approaches for hormone-refractory prostate cancer

Flora Stavridi, Eleni M. Karapanagiotou, Kostas N. Syrigos — 2010-01-27

Summary: Prostate cancer is one of the leading causes of cancer related death in men, and remains incurable in the metastatic setting. Despite the initial response to androgen deprivation, the disease gradually progresses to a hormone-refractory state due to cumulative genetic alterations in tumour cells or the microenvironment. Docetaxel represents the first chemotherapeutic agent with a small survival benefit for metastatic hormone-refractory prostate cancer (HRPC). In an attempt to improve survival benefit, several novel drugs targeting specific pathways involved in cell signaling, proliferation, angiogenesis, apoptosis and immune modulation are currently under investigation either as single agents or in combination with cytotoxic drugs. Clinical trials evaluate the inhibition of prostate cancer cells growth by targeting the nuclear receptor of vitamin D alongside cytotoxic therapy. Angiogenesis inhibitors as well as epidermal growth factor receptor blockage are also under clinical investigation in several combinations. Immunomodulatory agents and autologous dendritic cells or allogenic whole cell vaccines have progressed up to phase III trials. New drugs targeting bone microenvironment or apoptotic and proliferation pathways may enhance antitumour activity of chemotherapy in HRCP. Given the complexity of mechanisms underlying prostate cancer progression, future therapeutic strategies should rely on multidisciplinary approaches, thus exploiting newer molecular targets in concert with immunotherapy and cytotoxic chemotherapy. Here, we review the latest clinical evidence regarding the use of novel agents in HRPC.

The choice of the antigen in the dendritic cell-based vaccine therapy for prostate cancer

Lina Matera — 2009-12-02

Summary: Tumor antigens (TA) are promising candidates for targeted treatment of prostate cancer (PCa). Critical issues in the preparation of dendritic cell (DC)-based TA vaccines are the DC maturation state and the appropriateness of the TA. Prostate-specific antigen (PSA) and prostate acide pshosphatase (PAP) presented by DC have produced encouraging results and PAP-loaded DCs are at late-stage development for PCa patients. TAs indispensable for tumor survival and propagation are now emerging as first choice TAs for future vaccines. The increased expression and enzymatic activity of prostate specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA) by aggressive prostate tumors is indicative of a unique, selective advantage on the part of cells expressing them. Human telomerase reverse transcriptase (hTERT) and survivin are both involved in tumor cell survival and considered universal TAs. The T cell epitope potential of peptides derived from these TAs has been defined by computer-assisted prediction programs and has been tested in vitro and in vivo in terms of their ability to recruit cytotoxic T lymphocytes (CTL) and to be recognised as CTL targets. Results, reviewed here, show that anti-tumor immunity can be induced in vivo by DC loaded with both whole TAs and TA peptides. The promising, but still limited clinical success suggests further exploration of this immune therapy in the more appropriate setting of minimal disease. In advanced stages, vaccine can still be effective when combined with systemic or local cytoreductive therapies, which may overcome antigen specific tolerance and subvert the tumor immunosuppressive environment.

Exploiting cellular pathways to develop new treatment strategies for AML

Amir T. Fathi, Steven Grant, Judith E. Karp — 2010-01-07

Summary: The standard approaches to the treatment of acute myeloid leukemia (AML) have been predominantly based on cytarabine and anthracyclines. Yet, the outcomes associated with AML continue to be poor, especially for those patients who are older or carry higher-risk disease. In recent years, extensive research has led to the development and study of novel agents which target AML by diverse and varied mechanisms. Among these are targeted therapeutics such as kinase inhibitors and oligonucleotide constructs. These aim to suppress the production or activity of proteins, such as FLT3 and BCL2, among others, and thus disrupt related signaling cascades essential for leukemogenesis and proliferation. In addition, other agents like flavopiridol appear to target the myeloid blast by various mechanisms including suppression of cyclin-dependent kinases and interference with nucleotide synthesis. Another class of novel therapies includes inhibitors of histone deacetylase, which cause growth arrest and apoptosis through histone acetylation and resultant conformational changes. Clinical trials are now studying these and other agents alone and in combination with traditional cytotoxic therapies, with some encouraging results. In this review, we aim to provide a summary of the preclinical and clinical investigations of selected promising agents currently under study.

Forkhead box M1 transcription factor: A novel target for cancer therapy

2009-12-21

Summary: FoxM1 signaling has been reported to be associated with carcinogenesis. Therefore, the FoxM1 may represent a novel therapeutic target, and thus the development of agents that will target FoxM1 is likely to have significant therapeutic impact on human cancer. This review describes the mechanisms of signal transduction associated with FoxM1 and provides emerging evidence in support of its role in the carcinogenesis. Further, we summarize data on several FoxM1 inhibitors especially “chemopreventive agents” and these agents could be useful for targeted inactivation of FoxM1, which indeed could become a novel approach for the prevention and/or treatment of human cancer.

Approach to radiation therapy in hepatocellular carcinoma

2009-12-25

Summary: Hepatocellular carcinoma (HCC), the 5th most common cancer and the third most common cause of cancer-related death in the world with an estimated incidence of proximately 1 million new cases annually, has becoming a major global health problem in the world. A variety of treatment modalities, including resection, liver transplantation, transarterial chemoembolization (TACE), local ablative therapy and radiation therapy (RT) have been reported. Although partial hepatectomy and liver transplantation may offer the best chance of cure, only 15% of the patients have the chance to be treated by surgery when diagnosed. The effectiveness of systemic chemotherapy for HCC has been minimal, and local ablative therapy may offer comparable survival in patients with small HCC and preserve liver function. Recently, with developments in radiotherapy techniques, radiotherapy has been shown to play potential roles in a wide spectrum of HCC and to become more important so that it is necessary to evaluate the effect of radiotherapy in treatment of HCC. This paper is aiming mainly at the current radiation therapy strategies and their current advances, the optimal radiation therapy strategies will complement the current treatments and improve the treatment efficiency.

An integrated clinical approach for the identification, prevention, and treatment of tumor lysis syndrome

Tariq I. Mughal, A. Ahsan Ejaz, John R. Foringer, Bertrand Coiffier — 2009-12-25

Summary: Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic disorder that occurs when tumor cells undergo rapid decomposition spontaneously or in response to cytoreductive therapy. Delayed recognition of the metabolic imbalances caused by the massive release of tumor cell contents may result in clinical complications such as acute kidney injury, seizures, and cardiac arrhythmias. Prevention, the key principle in TLS management, relies on the identification of patients at risk for developing TLS during chemotherapy or because of disease progression. TLS-related risk factors pertain to tumor type (particularly hematologic malignancies), specific tumor characteristics (e.g. bulky tumor, high cellular proliferation rate, sensitivity to cytoreductive therapy), and other host-related factors. A comprehensive grading system proposed by Cairo and Bishop classifies TLS syndromes into laboratory or clinical TLS, thus facilitating TLS prevention and management. The mainstays of TLS management include monitoring of electrolyte abnormalities, vigorous hydration, prophylactic antihyperuricemic therapy with allopurinol, and rasburicase treatment of patients at high TLS risk or with established hyperuricemia. Urine alkalinization and use of diuretics remain controversial clinical practices. In this review, we describe the incidence of, risk factors for, and diagnostic characteristics of TLS and summarize strategies for the prevention and management of TLS-associated metabolic abnormalities, particularly hyperuricemia. We specifically highlight recently published TLS management guidelines, which focus on the prevention of TLS and hyperuricemia based on a patient’s level of risk, and the important role of nephrologists in the prevention and treatment of one of the most serious complications of TLS, acute kidney injury.

SRC kinase inhibition: Targeting bone metastases and tumor growth in prostate and breast cancer

Fred Saad, Allan Lipton — 2009-12-16

Summary: Prostate and breast cancer cells preferentially metastasize to bone, whereupon a complex interaction between metastatic tumor cells, osteoclasts, and osteoblasts results in the development of bone lesions that cause significant pain and patient morbidity. For patients with bone lesions, the goals of treatment are to decrease tumor growth, prevent further metastases, and inhibit tumor-associated bone pathology. Preclinical data suggest that SRC, a nonreceptor tyrosine kinase, is an important signaling molecule during the processes of osteoclast-mediated bone resorption, tumor growth, and metastasis, and that SRC has a role in hormone receptor signaling and resistance. As such, SRC represents a logical target for the treatment of advanced metastatic prostate or breast cancer. SRC-targeting agents, including dasatinib, saracatinib, and bosutinib, are currently in clinical development for patients with solid tumors. Preliminary data from phase 1/2 trials, including tumor responses and bone-specific activity in patients with prostate or breast cancer, demonstrate that SRC inhibitors have potential in the clinical setting. Data arising from ongoing and future clinical trials will confirm whether SRC inhibitors provide clinical benefits for patients with advanced disease.

Exercise and cancer rehabilitation: A systematic review

Rosalind R. Spence, Kristiann C. Heesch, Wendy J. Brown — 2009-12-07

Summary: Introduction: Cancer is increasingly being viewed as a chronic illness requiring long-term management, and there is a growing need for evidence-based rehabilitation interventions for cancer survivors. Previous reviews have evaluated the benefits of exercise interventions for patients undergoing cancer treatment and long-term survivors, but none have investigated the role of exercise during cancer rehabilitation, the period immediately following cancer treatment completion. This systematic review summarises the literature on the health effects of exercise during cancer rehabilitation and evaluates the methodological rigour of studies in this area to date.Methods: Relevant studies were identified through a systematic search of PubMed and Embase to April 2009. Data on study design, recruitment strategy, participants, exercise intervention, adherence rates, and outcomes were extracted. Methodological rigour was assessed using a structured rating system.Results: Ten studies were included. Breast cancer patients were the predominate patient group represented. Most interventions were aerobic or resistance-training exercise programmes, and exercise type, frequency, duration and intensity varied across studies. Improvements in physical functioning, strength, physical activity levels, quality of life, fatigue, immune function, haemoglobin concentrations, potential markers of recurrence, and body composition were reported. However, all studies were limited by incomplete reporting and methodological limitations.Conclusions: Although the methodological limitations of studies in this new field must be acknowledged, initial evidence indicates that exercise is feasible and may provide physiological and psychological benefits for cancer survivors during the rehabilitation period. Future studies with rigorous study designs are now required to advance the field.