Imatinib 'Treatment Holiday' Risks Disease Progression

Results from a randomized European trial published in the March 20 Journal of Clinical Oncology (JCO) show that patients whose advanced gastrointestinal stromal tumors (GIST) are controlled with the drug imatinib risk rapid progression of disease if treatment is interrupted.

Imatinib can provide tumor control and prolong overall survival in up to 90 percent of patients with advanced GIST. The side effects of imatinib are usually mild but often chronic. Because the standard of care for GIST is to administer imatinib until tumor progression or recurrence develops, patients who experience adverse effects from the drug sometimes request a treatment interruption if their cancer is under control. However, no clinical studies have looked at whether treatment interruption is safe for these patients.

Investigators randomly assigned 58 patients who had taken imatinib for more than 1 year and whose disease was under control to either continuation of treatment or treatment interruption. Of the 26 patients continuing treatment, 8 experienced disease progression. In the treatment interruption arm, 26 of 32 patients experienced disease progression, causing the trial to be stopped and physicians to recommend that all patients restart imatinib treatment.

Of the 26 patients in the treatment interruption arm who chose to restart imatinib, 24 again achieved tumor control. No difference in overall survival was seen between the two arms; however, explained the authors, the study was not designed to demonstrate equivalence in survival or increased resistance to imatinib after treatment interruption. They concluded that for GIST, "imatinib discontinuation…cannot be recommended in routine practice."

Annual Zoledronic Acid Increases Bone Density in Prostate Cancer Patients

A small, placebo-controlled, randomized clinical trial has shown that a single dose of zoledronic acid was sufficient to increase bone mineral density (BMD) over 12 months in men with nonmetastatic prostate cancer receiving gonadotropin-releasing hormone (GnRH) agonists, which have been associated with decreased BMD and increased fracture risk.

In the trial, published in the March 20 JCO, 40 men with nonmetastatic prostate cancer being treated with a GnRH agonist were randomly assigned to a single 4 mg intravenous dose of zoledronic acid or placebo. Of these, 36 patients completed BMD testing 12 months later. Participants on placebo experienced BMD decreases in the four bone locations assessed in the study. Participants given zoledronic acid, on the other hand, experienced BMD increases at the sites. The greatest cumulative BMD difference between the two groups, 7.1 percent, was seen at the posteroanterior lumbar spine, the portion of the vertebral column in the lower back. Zoledronic acid also decreased levels of N-telopeptide, a biomarker of activity of osteoclasts, cells involved in bone loss and remodeling.

Similar BMD improvements were seen in a trial in which zoledronic acid was given to prostate cancer patients every 3 months for 1 year. "The similarity of BMD results and persistent suppression of serum N-telopeptide," wrote lead author Dr. Matthew R. Smith from Massachusetts General Hospital, and colleagues, "suggest that annual zoledronic acid is sufficient to prevent bone loss in hypogonadal men."

The research team cautioned against overinterpreting the study, which was not powered to determine whether there was an impact on fracture risk. In an accompanying editorial, Dr. Celestia S. Higano from the University of Washington echoed this sentiment, arguing that the results do not mean that zoledronic acid can be used less frequently when treating prostate cancer patients with bone metastases "if the intention is to decrease the risk of skeletal complications."

Surgery Does Not Improve Survival for Advanced NSCLC Patients

Patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC) who had surgery following induction chemotherapy did not have better overall or progression-free survival than patients who received radiotherapy following chemotherapy. These results are published in the March 21 Journal of the National Cancer Institute.

Dr. Jan P. van Meerbeeck of the University Hospital Ghent in Belgium and colleagues conducted a multicenter prospective randomized trial that included 579 eligible patients with stage IIIA NSCLC and positive lymph nodes (N2) from 41 institutions of the European Organisation for Research and Treatment of Cancer-Lung Cancer Group from December 1, 1994, to December 1, 2002.

Patients were given induction chemotherapy, which consisted of three cycles of cisplatin or carboplatin, with at least one other chemotherapy drug. Of the 579 eligible patients, 332 patients were randomly assigned to surgical resection or thoracic radiotherapy. One hundred fifty-four patients in each arm completed treatment as assigned. 

Researchers found that surgery didn't improve overall or progression-free survival in patients. The median survival time was 17.5 months in the radiotherapy arm and 16.4 months in the surgery arm. The 5-year overall survival rate was 14 percent for patients who received radiotherapy and 15.7 percent for those who had surgery, a difference that was not statistically significant.

In an editorial, Drs. David H. Johnson, Valerie W. Rusch, and Andrew T. Turrisi noted that the "data indicate that chemoradiation therapy remains an appropriate therapeutic strategy for the subset of IIIA NSCLC patients with preoperatively detected N2 disease. The results also emphasize the importance of careful patient selection for surgery and of the type of lung resection." They also commented, "As we move forward, it is our dream to also focus on prospectively validating putative molecular markers of prognosis, drug sensitivity, and resistance. Hopefully, these promising technologies can be used to guide patient selection and treatment decisions in the future."

Hodgkin Lymphoma Survivors Have Increased Lifetime Risk of Solid Cancers

Survivors of Hodgkin lymphoma (HL) likely have a significantly increased risk of solid cancers throughout their lives, according to a new study that analyzed several variables influencing risk in this patient population. Results from the international study, published online March 19 in JCO, give estimates of risk that can help in risk assessment and screening plans for survivors.

Investigators used data from 18,862 people with HL who had survived for at least 5 years after diagnosis, collected from NCI's SEER program and 4 European registries. Variables used in the risk model included sex, year of HL diagnosis, age at HL diagnosis, initial treatment received, and age at diagnosis of solid cancer.

Of the 1,490 solid cancers that were identified, approximately 850 were estimated to be in excess. The risk of developing a solid cancer depended on age at diagnosis of HL, attained age, and sex, with women diagnosed at young ages having the highest risk. The patterns of risk differed between types of solid cancer and the most common sites for excess cancer were the female breast, lungs, and colorectum.

For both colorectal and breast cancers, young HL survivors had absolute risks comparable to those observed in the general population in the age ranges in which screening would normally be recommended (age 50 and above for colorectal screening, age 40 and above for mammography), suggesting that HL survivors would benefit from earlier routine screening.