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Top Oncology and Hematology Stories: 2008 - Journal Watch Oncology and Hematology
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Top Oncology and Hematology Stories: 2008
A perspective on the most important research in the field from the past year
The physician-editors of Journal Watch Oncology and Hematology have selected 12 articles published during
the past year that we believe hold the greatest implications for clinical practice. Here are our choices for the top
stories in breast cancer, gastrointestinal cancer, genitourinary cancer, head and neck cancer, palliative care,
malignant hematology, and benign hematology.
Breast Cancer
One of the biggest stories of the year in breast cancer research was a recent Eastern Cooperative Oncology Group
(ECOG) study that demonstrated the anticancer activity of bevacizumab, a humanized monoclonal antibody
against vascular endothelial growth factor, which plays a dominant role in tumor angiogenesis (JW Oncol
Hematol Jan 15 2008). Results showed that median progression-free survival and overall response rates were
significantly better among breast cancer patients who received paclitaxel plus bevacizumab than among those
who received paclitaxel alone. On publication of these findings, antiangiogenesis therapy for breast cancer
became a standard therapy option for patients with metastatic breast cancer. Bevacizumab is the first
antiangiogenesis therapy for breast cancer to be approved by the FDA, although many other agents are being
investigated. These agents are unlikely to offer significant benefit as stand-alone treatments, but they seem to
provide an additive or synergistic effect when combined with other anticancer agents. The challenges that
remain include defining which patients are most likely to benefit from this type of therapy and managing
predictable side effects such as hypertension.
In another top story in breast cancer research, investigators discovered that, even though women in families
carrying BRCA1 or BRCA2 mutations are at higher risk for breast cancer than are those in noncarrier families,
other variables play into the penetrance of BRCA-associated disease (JW Oncol Hematol Jan 29 2008). Results
from the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) study, which involved more
than 2000 women with diagnoses of unilateral or bilateral breast cancer, showed that the presence of bilateral
breast cancer in a BRCA1- or BRCA2-positive family elevated breast cancer risk more than did the presence of
unilateral breast cancer. The implications are that other gene modifiers seem to be able to change the penetrance
of BRCA genes. The important message is that we should always take family history into account when
calculating breast cancer risk in individuals who test positive for deleterious mutations in BRCA1 or BRCA2
genes.
Breast-cancer researchers also examined how hormone-therapy (HT) use and hormone-receptor status affected
recurrence risk after treatment for early-stage disease (JW Oncol Hematol Nov 13 2007). The results of this
large, single-institution study of more than 2300 women support the notion that the biology of hormone
receptor–positive disease in users of HT differs from that in nonusers. Among users of HT, recurrence risk was
twofold lower for patients with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive tumors
than for patients with ER- and PR-negative tumors. Thus, HT users who have receptor-positive, early-stage
disease seem to have better outcomes than do those who have receptor-negative disease. The next step in
applying this information to advance clinical practice will be to develop appropriate interventions targeted
toward specific tumor biology — not only to prevent breast cancer but also to lower risk for recurrence when
breast cancer does occur.
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Gastrointestinal Cancer
Prior research indicated that KRAS-mutation status is predictive of response to cetuximab (Erbitux) in
colorectal cancer. In an expanded study comparing best supportive care with cetuximab treatment in patients
with refractory colorectal cancer, responses were seen only in those whose tumors were KRAS wild type (JW
Oncol Hematol Feb 19 2008). Progression-free survival and overall survival benefits also were seen only in
patients with KRAS wild-type tumors. Data from this and other trials are practice-changing in that they indicate
that all patients who are being considered for treatment with either cetuximab or panitumimab should undergo
tumor testing for KRAS mutations and that treatment should be reserved only for patients with KRAS wild-type
tumors.
Results of the START trial on the use of sorafenib (Nexavar) for the treatment of patients with hepatocellular
cancer represent a landmark in the management of this disease because sorafenib is the first systemic agent to
provide a survival benefit (JW Oncol Hematol Jul 23 2008). A new generation of clinical trials will follow,
including those designed to evaluate adjuvant sorafenib after hepatic resection or after local ablative procedures.
Combination or comparative studies of sorafenib with other novel agents also will be conducted.
Genitourinary Cancer
The antitumor activity of bevacizumab (in this case, combined with interferon) was demonstrated in yet another
epithelial cancer (advanced renal cancer). The results of this large phase III trial (JW Oncol Hematol Jan 8
2008) confirmed that patients with low- or intermediate-risk metastatic clear-cell renal cancer who received
interferon plus bevacizumab had significantly longer progression-free survival than did those who received
interferon plus placebo. The finding was important in that bevacizumab marks the fourth targeted agent now
available that has significant clinical activity against advanced renal cancer.
Head and Neck Cancer
Recurrent metastatic head and neck cancer remains a therapeutic challenge because no single agent or
combination therapy provides a clear survival advantage. In a phase III trial, cetuximab in combination with a
standard chemotherapy regimen improved survival when compared with chemotherapy alone (JW Oncol
Hematol Sep 11 2008). This is the first randomized trial to demonstrate such benefit for a new agent in the firstline treatment of patients with recurrent or metastatic squamous-cell carcinoma of the head and neck.
Until recently, the use of systemic therapy for patients with metastatic or recurrent thyroid cancer has been
limited because of the lack of effective agents. As a result of the growing understanding of the underlying biology
of thyroid cancer, targeted agents are being tested to determine their efficacy in this patient population. This
study of motesanib — an oral, multitargeted tyrosine kinase inhibitor of epidermal growth factor receptors,
platelet-derived growth factor receptors, and KIT stem-cell factor receptors — represents the first report of an
effective targeted agent for the treatment of recurrent metastatic thyroid cancer, thus altering the landscape for
treatment of this disease (JW Oncol Hematol Jul 15 2008).
Palliative Care
Severe opioid-induced constipation affects a substantial number of cancer patients and causes discomfort,
embarrassment, and diminished quality of life. Available agents for severe constipation have limitations
including unpredictability of response, inconvenient schedules and dosing, and poor patient tolerance. In a
randomized trial involving advanced cancer patients with opioid-induced constipation, researchers showed that
methylnaltrexone (a selective peripheral µ-receptor antagonist) was significantly more effective than placebo in
rapidly inducing laxation without impairing analgesia (JW Oncol Hematol Aug 12 2008). As such,
methylnaltrexone represents a new class of agents that is effective in alleviating constipation in this patient
population.
Malignant Hematology
Mantle cell lymphoma (MCL) remains incurable with standard treatment approaches. In an effort to improve
outcomes for MCL patients, the Nordic Lymphoma Group (NLG) conducted a phase II trial of an intensive
induction regimen that incorporated chemoimmunotherapy, high-dose cytarabine, and autologous stem-cell
transplantation (JW Oncol Hematol Sep 23 2008). In contrast to an earlier NLG trial, which showed continuous
relapse rates for most patients, this study revealed an apparent plateau after 5 years. Follow-up of these
promising results will determine whether these patients have been cured; in the meantime, the findings are
encouraging in that they show true improvements in outcomes for selected MCL patients. Studies are under way
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to verify the roles of high-dose cytarabine and rituximab as well as to evaluate the incorporation of newer agents
such as bortezomib into treatments for patients with this challenging form of lymphoma.
Benign Hematology
Recent benign hematology studies addressed the problems of patients having too many or too few platelets.
Revisiting previous research that showed high molecular-response rates among polycythemia vera (PV) patients
who received pegylated interferon (PEG-IFN) alfa-2a, researchers presented results of the completed study (JW
Oncol Hematol Nov 10 2008). In an intent-to-treat analysis, hematocrit, white blood cell count, and platelet
count declined in 37 of 40 patients; spleen size decreased in all those with splenomegaly. Remissions were
sustained in most patients, no thrombotic episodes occurred, and serious adverse events were infrequent. These
results support the continuing evaluation of interferon in the management of PV.
In a separate phase III study, investigators sought to raise platelet counts in patients with chronic immune
thrombocytopenic purpura (JW Oncol Hematol Feb 12 2008). Within 3 weeks of treatment with the
megakaryocyte-stimulating agent romiplostim (Nplate), platelet counts rose to >50,000/µL in 50% of patients;
moreover, for most patients, these responses persisted for longer than 6 months. PEG-IFN alfa-2a and
romiplostim are valuable additions to the armamentarium of the practicing clinician.
— The Editors
Published in Journal Watch Oncology and Hematology December 9, 2008
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