Therapeutic Advances in Medical Oncology

Recent advances in technology now permit robust and reproducible detection of circulating tumour cells (CTCs) from a simple blood test. Standardization in methodology has been instrumental in facilitating multicentre trials with the purpose of evaluating the clinical utility of CTCs. We review the current body of evidence supporting the prognostic value of CTC enumeration in breast, prostate and colorectal cancer, using standardized approaches, and studies evaluating the correlation of CTC number with radiological outcome. The exploitation of CTCs in cancer management, however, is now extending beyond prognostication. As technologies emerge to characterize CTCs at the molecular level, biological information can be obtained in real time, with the promise of serving as a ‘surrogate tumour biopsy’. Current studies illuminate the potential of CTCs as pharmacodynamic and predictive biomarkers and potentially their use in revealing drug resistance in real time. Approaches for CTC characterization are summarized and the potential of CTCs in cancer patient management exemplified via the detection of epidermal growth factor receptor mutations from CTCs in patients with non-small cell lung cancer. The opportunity to learn more about the biology of metastasis through CTC analysis is now being realized with the horizon of CTC-guided development of novel anticancer therapies.

Angiogenesis has been identified as a relevant target for melanoma experimental therapeutics, based on preclinical and clinical studies. A variety of angiogenesis inhibitors are currently being tested in both metastatic and adjuvant melanoma clinical trials. To date, the most promising evidence of benefit is based on a statistically nonsignificant trend in survival gain reported in a randomized phase II trial combining bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, with cytotoxic chemotherapy. Larger phase III studies are required to determine the true extent of clinical benefit with this class of agents. Key to these clinical trials is the need to include translational endpoints, since correlation of biological and clinical data will provide the opportunity to identify biomarkers predictive of treatment response. These biological studies will also aid our, as yet, poor understanding of the mechanism of action of angiogenesis inhibitors, as well as drug-related side effects. Finally, if these trials show meaningful clinical benefit, then careful consideration will need to be given when designing second-generation trials, in the light of novel gene-directed therapies currently showing promise in melanoma.

Transitional cell carcinoma of the urothelial tract is the second most common cancer of the genitourinary system and the fifth most common cancer in Western countries with more than 300,000 new cases per year worldwide. Following the introduction of cisplatin-based chemotherapy, median overall survival in patients with metastatic disease has doubled, demonstrating chemotherapy as an important treatment modality in advanced or metastatic disease. Patients ‘unfit’ to receive cisplatin-based chemotherapy are characterized by impaired renal function, impaired performance status, and/or comorbidity that preclude the use of cisplatin. In this review we summarize the different chemotherapeutic schemes, focusing on treatment options in cisplatin ‘unfit’ patients.

Synchronous or metachronous colorectal liver metastases (CLMs), although being the expression of systemic disease, allow a curative approach for about 25—35% of patients. Patients presenting with CLMs should receive a multimodal management in order to increase the number of patients undergoing R0 surgery and to decrease the rate of recurrence. Postoperative and/or pre-operative systemic chemotherapy shows beneficial impact regarding progression-free and overall survival, without increasing postoperative complication rates. Concerning the complex definition of resectability and the number of patients with ‘borderline’ resectable CLMs, pre-operative chemotherapy plays an important role in both the improvement of prognosis and ‘conversion’ to resectability. Duration of chemotherapy in the perioperative setting should not exceed 6 months. Current data do not recommend the use of locally applied chemotherapy using hepatic artery infusion after resection of CLMs. Liver surgery has made several advances extending resectability to a larger group of patients and decreasing local hepatic recurrence. Moreover, locally ablative procedures such as radiofrequency and selective internal radiation therapy have joined the armamentarium in the case of positive resection margins or unresectable disease. Future research will help in defining treatment regimens and approaches in this setting.