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Dittrich C.
Applied Cancer Research -- Institution for Translational
Research Vienna (ACR-ITR VIEnna), Vienna, Austria.
Pemetrexed, a new antifolate drug, has shown broad-spectrum
activity in multiple tumor types. Single-agent activity against
breast cancer in untreated patients reached 31% and, depending
on the type and degree of prior chemotherapy, response rates tended
to decrease stepwise from 28% in lightly pretreated patients (ie,
with only adjuvant chemotherapy or at maximum one chemotherapy
treatment for metastatic disease) to 8% in heavily pretreated
patients after exposure with anthracyclines, taxanes, and capecitabine.
No clear dose-response relationship could be established. The
results from an ongoing prospective, randomized, double-blind
phase II study of two different doses (600 mg/m(2) and 900 mg/m(2)
of single-agent pemetrexed) may elucidate this further. In addition,
analysis of specific gene profiles and clinical outcome with special
emphasis on pathways known to be important for antifolate activity
is ongoing. Combinations of pemetrexed with doxorubicin, epirubicin,
or cyclophosphamide have also been evaluated in separate phase
I/II trials. For the combination of pemetrexed with carboplatin
or gemcitabine, dose recommendations from phase I trials that
are not restricted to breast cancer have been used. The combination
of pemetrexed with gemcitabine or carboplatin has shown remarkable
activity. Further results on the use of a pemetrexed-plus-cyclophosphamide
combination will be provided by an ongoing prospective, randomized
phase II study.
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Pemetexed
What Is Pemetrexed?