Volume 7 Issue 3, March 2010

A minority of patients with primary central nervous system lymphoma (PCNSL) achieve a complete response to therapy and most patients have a poor prognosis. A recent randomized phase II trial demonstrated that the addition of high-dose cytarabine to high-dose methotrexate increases the complete response rate and improves patient outcome.

In Japan, it is quite rare for an investigator to submit an investigational new drug application to initiate a clinical trial and obtain approval of a drug on the basis of clinical trial results. This means that development of new therapies is currently driven almost entirely by pharmaceutical companies as opposed to independent investigators. Here, we provide our perspective on the reasons for this situation and advocate investigator-initiated cancer drug development as a means of increasing access to better therapies for Japanese cancer patients.

Chemoradiotherapy and surgical resection are important elements of multimodality treatment for patients with locally advanced rectal cancer. The optimum sequence of these modalities has been addressed in several randomized trials and preoperative chemoradiotherapy has been shown to be superior to postoperative treatment for a variety of end points.

The addition of hormonal therapy to radiation therapy improves survival in men with unfavorable risk prostate cancer. Yet, men with prostate cancer have higher rates of non-cancer death than the general population and most will die from causes other than their index malignancy. Co-morbid cardiovascular disease is strongly associated with cause of death and this raises the possibility that prostate cancer or its treatment increases cardiovascular disease risk and possibly mortality.

The success achieved in the management of children with acute lymphoblastic leukemia has now been extended to older adolescents and young adults, as demonstrated recently by Nachman and coauthors. The effectiveness of treatment with an intense multiagent chemotherapy protocol renders the use of allogeneic hematopoietic stem-cell transplantation in first remission questionable, and calls for careful evaluation of the use of this chemotherapy in this patient population.

Disappointing phase III results for thalidomide combined with gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer might be related to poor efficacy of targeted therapies in unselected patients. We argue that current trial designs are flawed because they expose large numbers of such patients to potentially harmful treatment, and suggest that future research strategies should prioritize identification of predictive markers.

A randomized phase III trial for advanced pancreatic cancer comparing gemcitabine with gemcitabine plus capecitabine has again demonstrated that combination chemotherapy provides no significant outcome advantage for patients. A marked change in treatment paradigm is essential if therapeutic interventions are to move beyond the persistently dismal outcome results for the majority of pancreatic cancer patients, as exemplified by the past decade of clinical research.

Breast cancer is a heterogeneous disease with different molecular drivers regulating its growth, survival and treatment response. Drug development efforts have resulted in agents against new molecular targets that are active against only those tumors with the targeted molecular alteration or phenotype. The authors critically discuss the recently established and investigational strategies for the treatment of the main breast cancer subtypes.

Melanoma is an increasing problem, especially in the elderly population. In this article, the authors highlight key aspects of the epidemiology, presentation, staging and management of melanoma. They also emphasize the need for greater understanding and awareness of this cancer to optimize patient outcomes.

Microsatellite instability (MSI) is a frequent molecular phenomenon of colorectal cancer and is associated with deficient DNA mismatch repair. This Review presents an overview of MSI, including its clinical features and applications. The authors discuss the prognostic and predictive value of MSI and how it can be used to improve our knowledge of other cancer subtypes.

Pancreatic adenocarcinoma is the most lethal of the solid tumors and most patients present with locally advanced or metastatic disease that precludes curative resection. Considerable efforts have been made during the past decade to identify better systemic treatments. The authors of this Review discuss the current standards of care for patients with locally advanced and metastatic pancreatic carcinoma, and outline future directions for the development of new treatment strategies.

Defective DNA mismatch repair (MMR) occurs in approximately 15% of sporadic colorectal cancers. Studies have shown that patients with MMR-deficient colorectal cancers have a more favorable prognosis, but evidence indicates these patients do not benefit from adjuvant 5 fluorouracil-based chemotherapy. The importance of determining MMR status to inform clinical decision-making for adjuvant chemotherapy in patients with stage II colon cancer is discussed.