News & Views in 2011

Data from three phase II trials of tumor-infiltrating lymphocytes demonstrate high and durable complete response rates in patients with stage IV melanoma. Improved clinical outcomes might be achieved by combining tumor-infiltrating lymphocytes with other novel immunotherapeutic agents.

In the phase III ACCORD 11 trial, FOLFIRINOX was associated with the longest survival ever reported for patients with metastatic pancreatic cancer (11.1 months). However, toxicities associated with the four-drug regimen will limit its use to patients with a good performance status.

On 11 March 2011, a magnitude 9.0 earthquake and subsequent tsunami caused unprecedented devastation in Japan. Over 20,000 people lost their lives or went missing and more than 100,000 people had to evacuate their homes. Many victims are patients with chronic diseases, including cancer, who face interrupted or discontinued therapy.

A randomized phase III study has reported significant improvements in R0 resection rate and overall survival associated with perioperative cisplatin and 5-fluorouracil treatment compared with surgery alone in patients with gastroesophageal adenocarcinoma. These data support the results of the randomized phase III MAGIC study that reported a 13% 5-year survival benefit from perioperative chemotherapy.

Despite the improved progression-free survival and overall survival demonstrated by cisplatin–gemcitabine chemoradiation in a phase III randomized trial in patients with stage IIB to IVA cervical cancer, the acute and chronic toxic effects urge caution before embracing this as a new treatment paradigm.

A recent publication presented objective evidence that patients with and without brain metastases perform similarly in phase I clinical trials for advanced-stage cancer. This finding supports what neurosurgeons and neuro-oncologists have long suspected; namely, that the presence of brain metastases need not mandate exclusion of patients from early-phase clinical trials.

Zoledronic acid is a potent bisphosphonate used as the standard therapy for the prevention of skeletal-related events in patients with solid tumors metastatic to bone. Three phase III studies have reported head-to-head comparisons of zoledronic acid with denosumab, an inhibitor of the RANK signaling pathway.

Does targeting VEGF improve the lives of patients with metastatic breast cancer? Since the E2100 trial, there has been uncertainty about the benefit and toxicities of anti-VEGF therapy. By evaluating the RIBBON-1 trial results, we ask is such therapy failing, and are we considering all variables when scrutinizing the data?

Outcomes in patients with peripheral T-cell lymphomas are poor and there are no established standards of care for patients in the relapsed and refractory setting, owing in part to the lack of multicenter, controlled clinical trials. Recently, encouraging results were reported in this setting with pralatrexate—a novel folate analog.

A phase III, randomized, placebo-controlled trial in 171 patients with advanced-stage pancreatic neuroendocrine tumors demonstrated a significant improvement in progression-free survival with sunitinib treatment. We discuss the results of this trial in the context of other studies that have assessed treatment of pancreatic neuroendocrine tumors.

The treatment of multiple myeloma has evolved rapidly with the use of the immunomodulatory agents thalidomide and lenalidomide as well as the proteasome inhibitor bortezomib. Cavo and colleagues recently reported results of a landmark phase III study comparing thalidomide–dexamethasone with bortezomib–thalidomide–dexamethasone in newly diagnosed multiple myeloma.

New data from the Primary Rituximab And Maintenance study provide the strongest support for the use of rituximab maintenance in patients with follicular lymphoma. However, further considerations of cost, inconvenience, toxic effects, efficacy of retreatment, and lack of survival benefit should focus future clinical research on more-effective induction strategies.

The recent failure of bevacizumab in the adjuvant setting has forced us to consider what has gone wrong. It is possible that with careful analysis and novel biomarkers, we may not yet have to lay bevacizumab to rest.

The importance of appropriate patient selection necessitates novel clinical trial design and biomarker-driven trials to allow delivery of the right drug to the right patient at the right time—personalized cancer medicine. The WIN Consortium promotes collaboration between critical stakeholders and offers diverse populations of cancer patients the opportunity to participate in clinical trials with new drugs and biologics that target their tumor.

Mediastinal staging of patients with lung cancer is used to avoid futile thoracotomies. Endoscopic, esophageal and bronchial ultrasound procedures are methods to identify involved lymph nodes. The ASTER study indicates that the sensitivity of these new techniques is high, reducing the number of futile thoracotomies and improving outcomes when combined with mediastinoscopy.

The use of whole-brain radiation therapy (WBRT) in the treatment of primary central nervous system lymphoma is controversial. A recent randomized study addressing the use of this therapy was flawed and questions remain about the use of WBRT in these patients.

ColoPrint^® is an 18-gene expression signature designed to predict disease relapse in patients with early-stage colorectal cancer (CRC). We discuss the potential impact of ColoPrint^® on clinical practice, and its contribution to our knowledge of CRC molecular heterogeneity.

The outcomes in bladder cancer treated with radiotherapy are suboptimal. Recently, Hoskin et al. reported improved survival in patients with bladder cancer treated with radiation therapy with concurrent hypoxia-modification therapy. These results are promising but must be viewed in the context of previous studies and alternative treatment approaches.

Imatinib was discontinued in patients with chronic myeloid leukemia (CML) who gained a complete molecular response (CMR). Of those patients with at least 12 months follow-up, 61% experienced recurrence, all of whom responded to rechallenge. The remaining patients maintained CMR, suggesting that imatinib may 'cure' a small proportion of patients with CML.

A long-term follow-up study that assessed the effect of daily aspirin on colorectal cancer incidence concluded that it significantly reduced the risk of colon cancer, but not rectal cancer. Detailed analysis of the findings indicate that it is too soon to recommend daily aspirin for cancer prevention in healthy individuals.