Preliminary clinical data presented at a poster session of the 1999
annual meeting of the American Society of Clinical Oncology (ASCO)
revealed that a significant number of patients with advanced
colorectal cancer respond to first-line treatment with raltitrexed
(Tomudex) in combination with oxaliplatin. The response rate of 59%
suggests that this regimen may be one of the more active combinations
under current investigation for the disease.
Physicians treating advanced colorectal cancer need new options
for their patients especially as response rates to traditional
therapies are generally in the 20% range, said lead
investigator J. F. Seitz, MD, of the French Federation Nationale des
Centres de Lutte Contre le Cancer, Marseille, France. The
response rate achieved in this study represents a potentially
exciting step forward which is worthy of further investigation.
Interim analysis of the phase II study also showed stable disease in
19 of the 59 patients evaluable for efficacy. The most frequent grade
3/4 toxicities reported were neutropenia (9% of cycles), elevated
transaminase levels (8%), and nausea/vomiting (4%). The overall
toxicity profile was judged to be manageable.
Phase I Trial Shows Efficacy as Second-Line Therapy
In another study also presented at a poster session, investigators
assessed raltitrexed plus bolus fluorouracil (5-FU) as second-line
therapy in patients with advanced colorectal cancer. Their results
suggested that this combination compares favorably to other
second-line regimens. This combination offers another
therapeutic regimen that may provide significant palliation and
improved survival following 5-FU failure, said the investigators.
In the phase I study from Memorial Sloan-Kettering, 37 patients (all
but 5 of whom had not responded to a prior modulated 5-FU regimen)
were given raltitrexed followed, after 24 hours, by a bolus injection
of 5-FU. There was no evidence of a dose-response relationship, but a
high proportion of patients showed disease stabilization. The most
common toxicity was short-lived, nondose-limiting neutropenia
(without fever). No grade 3 or 4 mucositis or diarrhea was observed.
Commenting on the significance of these data, Gary Schwartz, MD, of
Memorial Sloan-Kettering, New York, said, Combination
therapyand Tomudex combinations in particularhas been
associated with major tumor regression, manageable toxicity,
prolonged stable disease, and good quality of life.