National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
June 15, 2010 • Volume 7 / Number 12

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Cancer Research Highlights

Trials Point to More Treatment Options for Chronic Myeloid Leukemia

Short-term results from two phase III clinical trials suggest that patients with chronic myeloid leukemia (CML) may have new options for the initial treatment of their cancer. It’s still unclear, though, whether there will be a longer-term survival benefit from the drugs compared with the standard first-line treatment, imatinib (Gleevec). Some researchers said this information will be important in determining the optimal treatment for patients with newly diagnosed CML.

Data from both trials were presented last week at the ASCO annual meeting in Chicago and published online June 5 in the New England Journal of Medicine (NEJM).

The trials compared the drugs dasatinib (Sprycel) and nilotinib (Tasigna), respectively, with imatinib. Both drugs are second-generation agents that, like imatinib, target the molecular driver of CML, a fusion of the genes BCR and ABL. This fusion gene produces a protein that spurs the overdevelopment of white blood cells that is the hallmark of CML. In both trials, patients who received one of the new drugs had higher rates of complete cytogenetic response, meaning a complete disappearance of cells that contain the chromosome (known as the Philadelphia chromosome) that harbors the BCR-ABL fusion gene, than patients who received imatinib. They also had higher rates of major molecular response, a disappearance of virtually all cancerous cells.

In the 519-patient trial that pitted dasatinib against imatinib, dubbed DASISION, at the 12-month follow-up point the confirmed complete cytogenetic response rate was 77 percent for patients treated with dasatinib compared with 66 percent for patients who received imatinib. The rates of major molecular response were 46 and 28 percent, respectively.

The 846-patient trial involving nilotinib, dubbed ENESTnd, compared two different doses of nilotinib with imatinib. The confirmed complete cytogenetic response and major molecular response rates for patients who received either nilotinib dose or imatinib were very similar to what was seen in the DASISION trial. In both trials, the side effects were considered minimal and manageable.

Both drugs—which are already approved by the FDA to treat CML that no longer responds to or is resistant to imatinib—are more potent than imatinib. In addition, fewer mutations in the BCR-ABL target appear capable of conferring resistance to these drugs than to imatinib, explained Dr. Charles Sawyers, whose research helped lead to the development of imatinib, one of the first and most successful molecularly targeted cancer therapies.

“The data regarding response and side effects in the two studies certainly make a strong case for dasatinib or nilotinib as first-line therapy over imatinib,” Dr. Sawyers wrote in an accompanying editorial in NEJM. But because imatinib will be available as a generic drug in several years and given “the rising pressure to balance cost and efficacy,” he noted, imatinib may remain a first-line option.

In February, the FDA granted “priority review” for nilotinib, which is manufactured by Novartis, as a first-line CML treatment. In a news release, Bristol-Myers Squibb, which manufactures dasatinib, said the company is “in the process of submitting the DASISION data to worldwide health authorities this year” for approval of the drug as a first-line CML treatment.

Partial Breast Irradiation Safe for Some Women with Invasive Breast Cancer

In a randomized trial performed at 28 treatment centers in nine countries, women with breast cancer who received a single dose of radiation during breast-conserving surgery had the same likelihood of local disease recurrence as women who received a standard, weeks-long course of whole-breast external-beam radiation therapy (EBRT) after surgery. Results from the trial, dubbed TARGIT-A, were published June 5 in the Lancet.

The researchers, led by Dr. Jayant Vaidya of University College of London, randomly assigned 1,113 women to receive a single dose of approximately 20 Gy of intraoperative partial breast irradiation using a device called the Intrabeam and 1,119 to receive EBRT at a dose of 40 Gy to 56 Gy given in 15 to 25 fractions (with an optional booster dose at the end of treatment). All of the women were 45 years of age or older and eligible for breast-conserving surgery for a single invasive tumor. Patients with known lobular carcinoma were excluded from enrollment, but patients in the intraoperative treatment group who were found to have lobular carcinoma or other high-risk disease during surgery (about 15 percent of the intraoperative group) later received additional EBRT. Hormone therapy and chemotherapy were given to women in both groups as needed.

At 4 years after treatment, six women in the intraoperative radiotherapy group and five women in the EBRT group had experienced a recurrence of their cancer in the treated breast. The researchers will continue to follow both groups of patients to monitor for local recurrences and new primary tumors outside the area treated.

Tumor recurrence, the need for radiation therapy, and speed of recovery are all factors that patients take into account when choosing treatment, explained the authors. “Because the definitive treatment with radiation can be completed at the time of the surgery or shortly afterwards in a single session with targeted intraoperative radiotherapy,” they wrote, “two of the patients’ major concerns are immediately addressed, and perhaps fewer patients should feel obliged to choose mastectomy over breast-conserving surgery either because they live far away from a radiotherapy facility or to avoid prolonging their treatment.”

Chemotherapy Combo Improves Survival in Elderly Lung Cancer Patients

Survival can be improved in older patients with advanced non-small cell lung cancer (NSCLC) with the use of two chemotherapy drugs as opposed to a single agent, French researchers reported at the ASCO annual meeting. The findings come from a phase III clinical trial of 451 patients between the ages of 70 and 89, the first lung cancer trial to enroll strictly older patients. The trial was stopped early when an interim analysis showed a more than 4-month improvement in overall survival in patients receiving the chemotherapy “doublet” of carboplatin (Paraplatin) and paclitaxel (Taxol) compared with those receiving single-agent treatment with either gemcitabine (Gemzar) or vinorelbine (Navelbine).

In addition to improved overall survival, patients in the trial who were randomly assigned to receive both chemotherapy drugs had longer progression-free survival and higher tumor response rates than patients who received single-agent treatment, reported the trial’s lead investigator, Dr. Elisabeth Quoix of University Hospital in Strasbourg, France. The beneficial effect was seen “in most subgroups tested,” she explained during a press briefing, including patients with a poorer prognosis, such as smokers and those of more advanced age.

When the trial was launched in 2005, ASCO clinical guidelines recommended single-agent chemotherapy to treat advanced lung cancer in older patients, Dr. Quoix noted. These new findings establish “a new [treatment] paradigm for elderly patients with NSCLC,” she said.

Median overall survival in the combination therapy arm was 10.4 months, compared with 6.2 months in patients who received a single agent. One-year survival was 45 percent and 27 percent, respectively. The combination therapy was, however, associated with greater side effects, including a nearly fourfold increase in neutropenia, a dangerous decline of white blood cells.

According to a recent study, most elderly patients with advanced NSCLC don’t receive any chemotherapy, and those who do usually receive only single-agent therapy, explained Dr. Martin Edelman of the University of Maryland Greenebaum Cancer Center, during the plenary session presentation of the trial results. Dr. Edelman noted some concerns about the trial design, including the combination regimen that was chosen and its dosing schedule. Nevertheless, he continued, data from this trial and other clinical trials support the benefit of platinum-based combination chemotherapy in elderly patients and “should change day-to-day practice.”

Dr. Mark Kris, chief of the Thoracic Oncology Service at Memorial Sloan-Kettering Cancer Center, agreed. “Patients over the age of 70 should be treated just like anyone else,” Dr. Kris said during a press briefing, with therapy decisions guided by factors such as comorbidities and patient preference, among others.

Adding Radiation to Hormone Therapy Improves Survival in Locally Advanced Prostate Cancer

Results from an international phase III trial show that adding radiotherapy to androgen deprivation therapy (ADT) reduced the risk of death from prostate cancer by 43 percent in men with locally advanced disease. The data were presented last week at the ASCO annual meeting in Chicago.

Between 1995 and 2005, 1,205 men were randomly assigned to receive ADT plus radiation or ADT alone. Most of the men had stage T3/T4 disease. After a median follow-up of 6 years, 51 of the 603 men who received the combined modality therapy had died, compared with 89 of the 602 men who received ADT alone. Fewer than 2 percent of patients in either group experienced significant gastrointestinal toxicities. However, patients receiving radiation had more low-grade diarrhea and rectal bleeding.

“These results suggest that adding radiation therapy to the treatment plan for these patients could become part of standard therapy and should be considered,” said lead researcher Dr. Padraig R. Warde of Princess Margaret Hospital and the University of Toronto.

The researchers projected that fewer men who received ADT plus radiation would die from their prostate cancer over 10 years than would men who received ADT alone (15 percent versus 23 percent). Final results are expected in the next few years.

Known as Intergroup T-94-0110, the study was coordinated by the National Cancer Institute of Canada with participation by the Medical Research Council of the United Kingdom and the Southwest Oncology Group in the United States. Though the study was originally designed in 1993, “We believe the results are still relevant in 2010,” said Dr. Warde. “Close to 50 percent of patients with high-risk disease are [still] managed with ADT alone.” In fact, he said, the benefit of adding radiation may be underestimated because changes in technology over the last decade have enabled oncologists to deliver “much higher doses of radiation into the prostate than used in this study.”

Also in the News: Selenium Does Not Protect Against Second NSCLC Tumors

Study results presented at the American Society of Clinical Oncology (ASCO) annual meeting revealed that selenium is not effective for preventing a second primary lung tumor in patients treated surgically for early-stage non-small cell lung cancer (NSCLC). An estimated 1 to 2 percent of NSCLC patients develop a second primary tumor in the first year after surgery.

Patients in the double-blind intergroup study, led by the Eastern Cooperative Oncology Group, were randomly assigned to take a placebo or 200 mg of selenized yeast daily for 48 months. The study was launched in 2000 and spanned nearly a decade before being stopped early, in November 2009, after the independent data and safety monitoring board reviewed the data and found that selenium supplementation was unlikely to produce the anticipated benefit.

“This study reminds us that supplements are medicines, and we know if they work only if they are rigorously tested,” said Dr. Mark Kris, of Memorial Sloan-Kettering Cancer Center, at the ASCO press briefing.

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