Saturday, June 20, 2009

Gem, tax, dox and trabectedin for LMS

I know I'm leiomyosarcoma-centric! Eventually, I hope other volunteers will report developments in treating their subtypes. In the meantime, I want to discuss some LMS news that illustrates how confusing research can be for a patient trying to decide which chemo to do.

At ASCO, a poster from the French Sarcoma Group suggested that gemcitabine (Gemzar) + docetaxel (Taxotere) is not more effective than gemcitabine alone. One reason this matters is gemcitabine is less toxic than the g+d combo.

The study divided patients into those with uterine LMS and LMS that arose elsewhere. ULMS patients had better responses in general to the chemo, a pattern seen in other studies.

In contrast, a multi-center SARC trial in 2007 found g+d more effective than g alone in metastatic soft-tissue sarcoma, including LMS.

At a discussion session, Dr. Chris Ryan of Oregon Health & Science University in Portland, OR, noted that the French study had a relatively small number of patients. He said he wished there would be random trials comparing g+d to anthracyclines as a first-line treatment. Doxorubicin (Adriamycin) is an anthracycline that is often used as the first line of defense for LMS and some other sarcomas.

Another poster, from the UK, found g+d effective as a first-line treatment for metastatic LMS. But it didn’t compare g+d to g alone or doxorubicin.

Dr. Martee Hensley of Memorial Sloan-Kettering Cancer Center in New York reported on a SARC Phase 2 trial of adjuvant chemo for high-risk ULMS. Patients get four cycles of g+d, followed by four cycles of doxorubicin. The trial isn’t finished, but judging by the early data, she said, she expects patients to do better with adjuvant chemo. (See what I wrote about adjuvant chemo for soft-tissue sarcoma in general.)

To gain a better understanding, she said, doctors could do a trial in which some women got adjuvant chemo and others did not. The ones who didn't get chemo couldn’t get a placebo because they would know from the lack of side effects. Another option would be to compare adjuvant chemo with an aromatase inhibitor, she said, or to compare one chemo against another.

Dr. Hensley discussed problems with both the AJCC and FIGO staging systems for ULMS. She wants a nomogram that combines stage-specific variables with other factors. A good staging system matters because if you enroll patients who were going to do well anyway, it influences the results of a clinical trial, she said. From an MSKCC study:
Estimates of stage-specific PFS [progression-free survival] and OS [overall survival] for uterine LMS were altered substantially when using the AJCC versus FIGO staging system. Adjuvant treatment strategies should be tested in patients at substantial risk for disease progression and death. Neither the FIGO nor AJCC staging system is ideal for identifying such patients, suggesting a need for a uterine LMS-specific staging system to better target patients for trials of adjuvant therapies.
In other ASCO news, at least three studies noted again that trabectedin (also known as yondelis) has value in treating patients with liposarcoma and leiomyosarcoma. (Click here, here and here.)
-- Suzie Siegel

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