News & Views in 2010

An important phase III trial involving transplant-eligible patients with multiple myeloma compared bortezomib and dexamethasone (BzD) induction with the previous standard of care. BzD was associated with a higher overall response and a deeper response to therapy that translated to superior responses following high-dose therapy and autologous stem cell transplantation.

A randomized phase III trial of patients with stage II and III colon cancer showed no benefit of adding bevacizumab to standard adjuvant oxaliplatin plus fluorouracil and leucovorin. Despite suggestive evidence of a short-term benefit, these data and other similar findings dictate that adjuvant bevacizumab should not be used in colon cancer.

Microscopic deposits of tumor cells in regional lymph nodes can be detected using immunohistochemical techniques in patients without conventional histopathological evidence of lymph-node involvement. In the case of bile duct cancer, these micrometastases have an intermediate prognostic significance between that of positive and negative conventional pathology.

Rituximab has become the mainstay of systemic therapy for patients with follicular lymphoma and is associated with an improved outcome at both diagnosis and relapse, either as induction or maintenance therapy. The challenge lies in maximizing the benefit of this drug in a condition characterized by multiple relapses.

Survival of patients with high-risk early-stage breast cancer has been improved by chemotherapy administration at shorter dose intervals: 'dose-dense' therapy. Validation for this approach is provided by the AGO trial, which demonstrated the biggest survival advantage of any study of dose-dense chemotherapy to date.

The optimal chemotherapy regimen to be used concurrently with thoracic radiation for locally advanced non-small-cell lung cancer remains uncertain. Studies investigating this question are ongoing.

Incorporating hematopoietic growth factors into chemotherapy regimens is a common method for mitigating toxicity of dose-intensive regimens. A clinical trial has shown that G-CSF can counteract acute toxicities, permitting further dose intensification of induction chemotherapy. However, the effects of these strategies on long-term toxicities and overall survival remain undefined.

One of the seven ongoing trials of accelerated partial breast irradiation (APBI) has concluded that single-dose intraoperative radiotherapy should be considered as an alternative to protracted whole-breast irradiation. With a median follow up of 2 years, such conclusions seem premature. Until the risk and pattern of breast recurrence is reported at longer follow up, TARGIT APBI should remain an experimental approach.

The IAEA-ACC study compared accelerated radiotherapy with standard radiotherapy in a multicenter trial conducted in developing countries. Advantages were most notable in patients with early-stage disease, which may limit the utility of this therapy. In countries where resources are limited, however, this strategy may be a cost-effective approach to improving outcomes in patients with head and neck cancer.

Two meta-analyses of the Non Small Cell Lung Cancer Meta-analyses Collaborative Group (NSCLC MACG) on the effects of adjuvant chemotherapy on early stage NSCLC after complete or curative resection have demonstrated that adjuvant cisplatin-based regimens are a valid and recommendable option following curative surgery. We discuss these results in the light of current interdisciplinary guidelines and existing meta-analyses of randomized clinical trials.

Adding lomustine to the standard combination of idarubicin and cytarabine for the treatment of old patients with acute myeloid leukemia improves complete response rates and overall survival. These findings emphasize the importance of dose intensity and raise the question of a unique role for nitrosoureas in the treatment of this disease.

Whether a 70-gene signature could help individualize therapy in breast cancer patients with small tumors is the subject of a recently reported study. The authors of the article raise important issues about how to validate the clinical utility of the new molecular classifiers for risk prediction.

The ZODIAC trial reported that the addition of vandetanib to docetaxel in second-line treatment of unselected patients with metastatic non-small-cell lung cancer resulted in a statistically significant improvement in progression-free survival compared with docetaxel alone. Identification of biomarkers to assist in molecular selection of patients for targeted therapy is a tool for 'smart' clinical trial design.

A clinical trial of patients with pharmacogenomically selected non-small-cell lung cancer clearly demonstrated an improvement in progression-free survival after gefitinib treatment compared with standard chemotherapy. This report is the first to suggest that personalized therapy based on pharmacogenomics could be standardized in the treatment of lung cancer.

The efficacy of nilotinib and dasatinib as frontline treatment of chronic myeloid leukemia has been documented in small phase II studies. Now, two clinical trials have assessed the effectiveness of second-generation tyrosine kinase inhibitors in comparison with standard dose imatinib at 1 year. Will these results change our current practice?

A randomized phase III trial that assessed treatment with cisplatin plus gemcitabine or gemcitabine alone for patients with advanced biliary tract cancer has provided evidence for a new standard treatment option for these patients. The therapeutic outcome (that is, overall survival, disease-free survival, and disease control rate), was significantly better in the combination arm with no increase in toxic effects.

Doublet fluoropyrimidine-based chemotherapy is the standard of care for the first-line treatment of metastatic colorectal cancer (mCRC). However, single fluoropyrimidine-based therapy remains an important alternative. In this article, we highlight the potential impact of a recent trial assessing the addition of bevacizumab to capecitabine in the first-line treatment of mCRC.

Adjuvant vaginal brachytherapy was compared with adjuvant pelvic radiation therapy in patients with high-intermediate-risk uterine cancers in the PORTEC-2 trial. The results suggest that vaginal brachytherapy is the treatment of choice; however, the inclusion of very few patients with grade 2 or 3 disease limits generalizability of the results to these subgroups.

Ovarian cancer that recurs more than 6 months following primary chemotherapy can respond to many different drugs, but retreatment with a combination of carboplatin and paclitaxel has become a standard of care. A combination of pegylated liposomal doxorubicin and carboplatin may provide a slightly, but significantly, greater therapeutic index than carboplatin and paclitaxel.

A study by Atkin and coauthors has demonstrated reduced mortality by screening average-risk patients with a single use of flexible sigmoidoscopy for colorectal cancer. This large UK trial of 170,432 subjects aged 55–64 years (median 60.2 years) randomized patients 2:1 to control or single flexible sigmoidoscopy. Reduction in colorectal cancer incidence was 23% and cancer mortality was reduced by 31% in the intention-to-treat population. In this News & Views article we discuss the role of flexible sigmoidoscopy in population-based screening for colorectal cancer.