IMATINIB PROMISING FOR CHORDOMA

NEW YORK (Reuters Health) Mar 06 - Imatinib appears to slow progression of advanced chordoma, according to findings from a phase II trial.

"The study that we published has some limitations, yet imatinib can be active in advanced chordoma, a very rare disease that lacks any treatment for the advanced phase," Dr. Silvia Stacchiotti from Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, told Reuters Health in an email.

Based on promising results from six patients, Dr. Stacchiotti and colleagues went on to test imatinib in 56 patients with advanced chordomas that expressed either progressive platelet-derived growth factor receptor beta (PDGFRB) or platelet-derived growth factor beta (PDGFB), or both.

Median treatment duration was 9.1 months, and median follow-up for overall survival was 26.4 months, according to a report online February 13 in the Journal of Clinical Oncology.

Among 50 evaluable patients, there was one partial response (2%). Thirty-five patients (70%) had stable disease, and the other 14 (28%) had disease progression.

The clinical benefit rate (partial response plus stable disease for at least six months) was 64.1% for the intent-to-treat population.

PET scans at three months showed 10% decreases in maximum standard uptake value (SUV) in 13 patients and 25% decreases in 10 patients.

Among the 39 patients with a response or stable disease at three months, 33 remained responsive or with stable disease at six months.

The median for progression-free survival was 9.2 months, and the median for overall survival was 34.9 months.

Among 20 patients assessed for pain at six months, eight had improvement, five had no change, and seven had worse pain. Overall, pain had not worsened in 65%.

Most patients experienced significant toxicity, including chronic anemia, fatigue, and fluid retention.

"These results should be viewed as hints of antitumor activity, rather than a formal demonstration of efficacy," the researchers say.

"We are now running a phase II study on imatinib (plus) everolimus in advanced chordoma," Dr. Stacchiotti said. "No standard/approved medical treatments are available; only experimental approaches."

"Another phase II study on lapatinib in advanced chordoma has just closed the enrollment," he added.

In an editorial, Dr. Stefan Sleijfer from Erasmus University Medical Center in Rotterdam, The Netherlands, and Dr. Andrew J. Wagner from Dana-Farber Cancer Institute in Boston ask, "Do we have enough data to conclude that imatinib is effective in chordoma?"

"On the basis of the data presented by Stacchiotti et al., are we at go or no go for imatinib in chordoma? It is difficult to determine," they write.

"In this era," they caution, "with more agents to test in smaller, more specific cohorts of patients, we can no longer afford minimally active drugs to pass phase II studies and to enter phase III trials."

SOURCE: http://bit.ly/zzc6d0

J Clin Oncol 2012.