Reviews & Analysis

The optimal age-specific treatment approach for adolescents with Hodgkin lymphoma (HL) is controversial. Here we discuss the results of a recent retrospective analysis that compared the outcomes for adolescents with those of young adults with HL treated with regimens normally recommended for adults. The investigators conclude that adult treatment protocols are a safe and effective treatment option for adolescents with HL, but the results do not consider late treatment toxicity that may impact quality of life and survival.

The results of a randomized, controlled trial investigating the neurocognitive effects of stereotactic radiosurgery (SRS), with or without whole-brain radiation therapy (WBRT), to treat brain metastases demonstrated a significant reduction in learning and memory, associated with the addition of WBRT to SRS. The results indicate that SRS monotherapy is an effective and safe initial management strategy for brain metastases.

Patients who undergo hepatic surgery for initially resectable liver metastases from colorectal cancer have a 70% risk of relapse. A recent phase III randomized trial has failed to demonstrate an improvement in disease-free survival with the addition of irinotecan to 5-fluorouracil and folinic acid as adjuvant treatment for patients with radically resected colorectal cancer with liver metastases.

The addition of zoledronic acid to aromatase inhibitors is associated with improved bone mineral density, but not with an effect on clinically-meaningful end points such as fractures. The oncology community should prioritize the design of trials evaluating more relevant end points, such as fragility fracture risk, for treatment-induced bone loss and critically assess the effects of such treatment on breast cancer survival.

The effect of PSA level on distant metastases and cause-specific mortality was assessed in a recent study, and showed a nadir PSA level 1.5 ng/ml within 2 years of radiotherapy treatment predicts distant metastases and death from prostate cancer.

EGFR inhibitors provide benefit in patients with advanced and metastatic head and neck squamous cell carcinoma (HNSCC). Mass spectrometry profiling has been used to predict outcome in patients with HNSCC after EGFR inhibitor treatment, and may enable prior identification of patients most likely to benefit from these therapies. However, further validation in prospective studies is needed.

Dose-dense administration of paclitaxel as well as intraperitoneal administration of platinum and paclitaxel as first-line treatments provide similar advantages compared with standard treatment in advanced ovarian cancer. Both approaches, however, need to be confirmed by additional studies. A low dose of pegylated liposomal doxorubicin combined with carboplatin is superior to standard paclitaxel and carboplatin in relapsed platinum-sensitive ovarian cancer.

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.

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.

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.

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.

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.

Chemotherapy options for patients with extensive-stage small-cell lung cancer (SCLC) are limited. A recent phase III trial assessed the combination of carboplatin and pemetrexed but this regimen produced inferior survival results compared with the standard carboplatin and etoposide regimen. The combination of carboplatin and etoposide remains the standard first-line chemotherapy option for the treatment of patients with extensive-stage SCLC.

Activating mutations in EGFR are characteristic of patients with lung cancer who have high sensitivity to EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib. The randomized IPASS study by Mok and colleagues confirmed that patients with EGFR mutations have a higher response rate, longer progression-free survival and improved quality of life when treated with first-line gefinitib instead of chemotherapy.

Dose-dense chemotherapy has been proposed to improve breast cancer outcome due to its ability to prevent cancer cell repopulation; however, little is known about which patients benefit most from such scheduling. A pooled analysis of studies assessing dose-dense adjuvant chemotherapy has shown that most of the therapeutic benefit derived from dose-dense scheduling arises in patients with node-positive, triple-negative disease.

First-line platinum and taxane chemotherapy improves the prognosis of patients with epithelial ovarian cancer (EOC), however, about 80% of patients relapse and long-term survival is poor. The development of drug resistance is the main cause of treatment failure; therefore, the identification of new compounds that interfere with tumor growth and survival is a priority.

We reviewed the results of the Gynecological Oncology Group 204 (GOG-204) randomized phase III trial, which investigated four cisplatin combination chemotherapy regimens for the treatment of patients with recurrent or metastatic cervical carcinoma. As the overall survival was similar between all arms, treatment recommendations need to be tailored based on toxic effects.

Currently, acquisition of tissue from presumed metastatic deposits in breast cancer is not routine. Instead therapeutic decisions in this setting are based on the features of the tumor at initial diagnosis. As biopsies are diagnostic and changes can occur between the primary and the secondary tumors, the routine biopsy of suspected metastatic deposits needs to be considered. Such biopsies will also be key to translational research, which will underpin future therapeutic advances.