National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
April 17, 2012 • Volume 9 / Number 8

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Cancer Research Highlights

Many Patients with Cancer Need Better Treatments for Pain

Inadequate pain treatment in patients with cancer remains a significant problem and appears to be more frequent among minorities, according to a new study. The findings were published online April 16 in the Journal of Clinical Oncology.

Dr. Michael Fisch of the University of Texas MD Anderson Cancer Center and his colleagues surveyed more than 3,000 patients with invasive forms of breast, prostate, lung, and colorectal cancer who were likely to have pain. The patients were treated at academic medical centers and community-based hospitals.

More than two-thirds of patients reported pain or requiring analgesics for pain control at their initial oncology appointment. Based on reported pain levels and the type and/or dose of prescribed pain medication, the researchers found that one-third of these patients received inadequate treatment for their pain.

Approximately 40 percent of patients who experienced moderate to severe pain did not receive the proper pain medication, and 20 percent of patients with severe pain received no pain medication. In surveys done after follow-up visits with their oncologists 4 to 5 weeks later, patients reported little improvement in pain management. One month is a fairly short follow-up period, the authors acknowledged, as effective pain management usually requires monitoring and adjustments.

Minority patients were nearly twice as likely as white patients to receive inadequate pain treatment, the researchers found. The disparity in adequate pain treatment among minority groups could be due to multiple factors, they wrote, including communication problems and patient trust issues, as well as “system issues,” such as drug availability.

In addition, patients with earlier stages of cancer reported inadequate pain management at different time points after diagnosis. This indicates not only that patients with early-stage cancers need better pain management, but that the medical profession should better characterize pain symptoms and identify pain sources, noted Dr. Worta McCaskill-Stevens of NCI’s Division of Cancer Prevention (DCP) and a co-author of the study.

“This study is a stepping stone to better evaluation of pain,” she said, noting that doctors adhere more closely to other treatment guidelines than to pain management guidelines.

“Only one in six responding medical oncologists [in the study] reported frequent referrals to specialists in either pain or palliative care,” wrote Drs. Martin Stockler and Nicholas Wilcken in an accompanying editorial. “Clearly more work is needed, perhaps in medical school, but certainly in residency and fellowship programs.”

This is an issue that goes beyond physicians, noted Dr. Ann O’Mara, head of palliative care research in DCPand a co-author of the study. Nurses and other health care staff should also receive more training in this area, she advised.

Further reading: “Survey of Oncologists Suggests Lack of Progress in Cancer Pain Management

More Chemotherapy May Help after Initial Treatment for Childhood Leukemia Fails

A small percentage of children diagnosed with acute lymphoblastic leukemia (ALL) responds poorly to initial chemotherapy. When this initial treatment, called induction therapy, fails to induce a complete clinical remission, most leukemia experts would recommend an allogeneic stem cell transplant. However, a new study suggests that at least some of these children may do better if they receive additional chemotherapy rather than a stem cell transplant.

Reporting their findings in the April 12 New England Journal of Medicine, the researchers noted that doctors can cure 8 in 10 children newly diagnosed with ALL. But certain subgroups of patients tend to do worse than others. For instance, patients whose cancers do not go into complete clinical remission after 4 to 6 weeks of induction therapy are at high risk for poor outcomes.

To determine the optimal treatment for these patients, the researchers analyzed data on more than 44,000 children who participated in ALL clinical trials around the world. Of these children, 1,041 had cancers that responded poorly to induction therapy. Most of these patients went on to have a stem cell transplant, but some received only additional chemotherapy.

A subset of the children whose cancers did not respond to induction therapy unexpectedly showed better long-term survival with chemotherapy alone than with stem cell transplantation. These children were younger than age 6, had precursor B-cell ALL rather than T-cell ALL, and had no other high-risk clinical or genetic features.

More than 70 percent of the children in the subgroup that received additional chemotherapy rather than a stem cell transplant survived at least 10 years, which was more than twice the survival rate of the entire group of patients who did not respond to induction therapy.

“This study tells us that the failure of induction therapy should no longer be considered an automatic indication for a bone marrow transplant,” said co-author Dr. Ching-Hon Pui, chair of the St. Jude Children’s Research Hospital department of oncology. “[But]a 72 percent survival rate is still not acceptable, and we need to find better ways to treat these patients,” he added.

The study also demonstrates “the power of large collaborative efforts to discover important new insights into disease,” said Dr. Karen Rabin of Baylor College of Medicine, who wrote an accompanying editorial. The benefit of chemotherapy for these patients emerged only after 14 research groups on three continents combined their results.

For Older Patients with Leukemia, Low Doses of Gemtuzumab Improve Survival

In a randomized trial, patients aged 50 to 70 with previously untreated acute myeloid leukemia (AML) who received the targeted therapy gemtuzumab ozogamicin (Mylotarg) in addition to standard chemotherapy lived longer than patients who received standard chemotherapy alone. These results, published online in The Lancet on April 4, counter some earlier studies that indicated that the drug was ineffective and too toxic.

Gemtuzumab received accelerated approval for AML from the Food and Drug Administration (FDA) in 2000, but the confirmatory clinical trial required for full approval showed that the drug did not improve survival and increased toxicity, including the risk of treatment-related death. The manufacturer, Pfizer Inc., voluntarily withdrew the drug from the general market in 2010, though clinical trials have continued.

In the current trial, which was conducted by the Acute Leukemia French Association, the researchers used a lower dose given over 3 days during chemotherapy instead of a higher dose given over 2 days to reduce side effects. In the study, 139 patients received standard chemotherapy with the drugs daunorubicin and cytarabine, and 139 received standard chemotherapy plus gemtuzumab ozogamicin.

The addition of low, fractionated doses of gemtuzumab ozogamicin improved overall survival and event-free survival (time to relapse, death, or assessment that the disease is not responding to treatment). After 2 years of follow-up, event-free survival was 41 percent for the patients who received gemtuzumab ozogamicin and 17 percent in the control group. Overall survival 2 years after treatment was 53 percent in the gemtuzumab ozogamicin group and 42 percent in the control group.

Although patients in the gemtuzumab ozogamicin group were more likely to experience side effects, particularly more-persistent reductions in white blood cells and platelets, deaths during treatment did not differ significantly between the two groups. “The use of fractionated lower doses of gemtuzumab ozogamicin allows the safe delivery of higher cumulative doses and substantially improves outcomes in patients with acute myeloid leukemia,” wrote the authors.

“These results are quite important if confirmed [in additional trials],” commented Dr. Wyndham Wilson of NCI’s Center for Cancer Research, who was not involved in the research. Few advances have been made in the treatment of older patients with AML in recent years, he added, and effective new drugs are badly needed.

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