Data from a phase I clinical trial of CT-2584, a novel
small-molecule, anticancer, antiangiogenesis drug under investigation
for the treatment of chemotherapy-resistant (advanced and refractory)
cancers were presented at the 34th Annual Meeting of the American
Society of Clinical Oncology in Los Angeles.
The data were reported by Roger Waltzman, MD, lead author. David
Spriggs, MD, is the senior author and principal investigator for the
trial, which is being conducted at the Memorial Sloan-Kettering
Cancer Center in New York City. The study is designed to establish a
maximum tolerated dose of CT-2584, develop a pharmacokinetic profile
of the drug, and evaluate its antitumor effects. This study is a
companion to one being conducted at Christie Hospital in Manchester, England.
In this study, CT-2584 is administered intravenously over 6-hour
infusions for 3 consecutive days, followed by 18 days during which no
CT-2584 is administered. This constitutes one cycle of therapy. If no
dose-limiting toxicities are observed during the first cycle, a
second cycle of therapy is administered. Patients who have received
two cycles are evaluable for antitumor response. Patients whose
cancers have become stable or have decreased in size are eligible to
receive up to a total of six cycles of CT-2584 therapy.
In the United States, 23 patients have been enrolled in the trial, 22
at Memorial Sloan-Kettering and one under a compassionate study using
the Memorial Sloan-Kettering protocol described above. All 23
patients are evaluable for toxicities, with 18 evaluable for tumor response.
To date, no dose-limiting side effects, such as severe nausea and
vomiting, low blood counts, or gastrointestinal damage, have been
observed. Of the 18 patients evaluable for tumor response, 13 remain
alive at a median of 8 months (range, 2 to 19 months) after treatment
with CT-2584. Five patients (27%) have experienced tumor stabilization.
Carolyn Paradise, md, head of medical affairs at Cell Therapeutics,
producers of the drug, stated: "We continue to be impressed with
the activity of CT-2584 seen in these early trials and by the
tolerability profile of the drug. Combined with patients enrolled in
our CT-2584 trial in the United Kingdom, we have treated more than 50
patients, 35 of whom were evaluable for tumor response to CT-2584. It
is exciting that 10 (29%) of these patients cancers stabilized
on CT-2584, and that 7 are still alive after a median of 10 months
following treatment. Overall survival for all 35 evaluable patients
in both trials is also very encouraging with 21 alive a median of 10
months after starting treatment with CT-2584. With this tolerability
profile, synergistic effects with certain standard chemotherapeutics,
and the possibility of oral administration, chronic longer-term
outpatient therapy may be possible. This could be a major benefit for
Drug Shows Particular Promise in Advanced Prostate Cancer and Sarcomas
According the James A. Bianco, MD, president and CEO of Cell
Therapeutics, CT-2584 appears to be particularly promising in the
treatment of patients with advanced prostate cancer and sarcomas.
"We believe this to be attributable both to the direct tumor
toxic effects of CT-2584 and to its potent antiangiogenic
effects," said Dr. Bianco. "Based on the results observed
thus far, we plan to begin phase II trials this year in both advanced
prostate cancer and in advanced sarcomas.
It is believed that CT-2584 has a unique mechanism of action of
tumor-cell killing. This mechanism involves CT-2584s effect on
tumor-cell phospholipids, such as phosphatidic acid, which are
believed to play an active role in neoplastic cell transformation. In
preclinical studies, CT-2584 was effective in vitro against a broad
array of tumor cell types, including those resistant to multiple
kinds of chemotherapy drugs at drug levels that were nontoxic to
normal human bone marrow cells. In addition, CT-2584 significantly
inhibited cancer cell-induced angiogenesis at drug levels below which
cancer-cell killing was observed.