From old to new agents

[Guest guest]

This year's American Society of Clinical Oncology meeting featured a highly

select lineup of sessions dealing with hematologic malignancies. Over the past

decade, we have seen much progress in the treatment of blood cancers, but

continuing improvement of outcomes will depend on the identification of novel

therapies and the accurate determination of which patients will benefit from

these therapies. Meetings such as these generate the necessary synergies that

bring promising new agents from bench to bedside. Below are several

presentations that highlight a fraction of the important work presented at 2010

meeting.

According to lead author, E. Cortes, MD, at 24 months of follow-up, 77% of

imatinib (Gleevec)-resistant patients and 86% of imatinib-intolerant patients

who were treated with the investigational drug were alive without evidence of

disease progression, and median progression-free survival has not yet been

reached in either group.

Moreover, responses to second-line therapy with bosutinib (SKI 606) were seen

across a variety of BCR-ABL mutations, and the drug had a favorable toxicity

profile, with manageable, self-limiting gastrointestinal adverse events, low

rates of hematologic toxicity, and minimal fluid retention.

In the oral abstract session, Deborah A. , MD reported study results on

behalf her colleagues that found that allogeneic transplantation confers a

significant survival advantage, particularly among younger patients, when

treating Philadelphia chromosome-positive acute lymphoblastic leukemia with a

regimen that adds imatinib to hyper-CVAD chemotherapy.

Among 109 patients who did not have hematologic responses at baseline (that is,

no hematologic response to imatinib), 102 had a response to bosutinib, and 99 of

these response were complete responses. Major cytogenetic responses were seen in

136 of 214 patients who did not have cytogenetic responses to imatinib, and 106

of these patients had complete cytogenetic responses. Major molecular responses

were seen in 79 of 151 patients who lacked such responses at baseline, and

complete molecular responses were seen in 49.

The responses occurred rapidly, with median time to complete hematologic

response occurring within 1 month. Median time to complete molecular response

was 6.3 months, and to complete cytogenetic response was 12.3 months. The

response rate curves continue to rise into the second and third years of

therapy, Dr. Cortes said.

Treatment-emergent grade 3 or 4 adverse events included diarrhea and rash (each

occurring in 9% of patients), vomiting in 3%, and nausea and asthenia in 2%

each. Diarrhea was usually self-limited. In all other categories, the incidence

of grade 3 or 4 events was 1% or lower. Hematologic laboratory abnormalities

include thrombocytopenia in 24%, neutropenia in 16%, and anemia in 12%.

Nearly half of all patients discontinued therapy, primarily because of adverse

events (19%). Disease progression led to discontinuations in 5% of

imatinib-intolerant patients and 15% of resistant patients. Other reasons for

discontinuation included unsatisfactory responses, patient or investigator

request, or being lost to follow-up. There were five deaths among the resistant

patients, but NONE IN THE INTOLERANT GROUP.

http://tinyurl.com/4lvsuzs

FYI,

Lottie Duthu