Based on the positive results of two independent, corroborative,
placebo-controlled phase III clinical studies in head and neck
cancer, Matrix Pharmaceuticals, Inc, has announced plans to submit a
new drug application for a cisplatin/epinephrine injectable gel
(IntraDose) by the end of this year. The results of these clinical
studies were presented at the 36th annual meeting of the American
Society of Clinical Oncology (ASCO).
Both phase III trials showed cisplatin/epinephrine therapy to be
effective in reducing the size of tumors in late-stage recurrent or
refractory head and neck cancer patients. Moreover, the tumor
response proved beneficial to the patient in both studies.
These results are impressive for this disease and the stage and
type of patients who were treated, said Michael D. Casey,
chairman and CEO of Matrix. All of the patients had refractory
or recurrent disease, had been heavily pretreated with other
therapies, and were very late in the course of their disease. Over
85% of these patients were previously treated with surgery and
radiation therapy, and half of those had also been treated with
The protocols for the two trials were identical except for geographic
location, allowing assessment on both a combined and individual
basis. Objective tumor response was evaluated for the primary target
tumor identified by the clinical investigator prior to treatment.
Patient benefit was determined using treatment goals (eg, pain
control, mobility, ability to hear) that were selected beforehand by
both the clinical investigator and the patient. A total of 178
patients were evaluated.
On an intent-to-treat basis, 29% of patients treated with
cisplatin/epinephrine achieved an objective tumor response, vs 2% for
the placebo, a statistically significant result (P < .001).
Approximately twice as many patients (19%) achieved complete
responses as partial responses (10%).
The preselected patient benefit goal was attained in 27% of the
cisplatin/epinephrine-treated patients vs 12% of the placebo-treated
patients (P = .046). The association of objective tumor
response with attainment of the preselected patient goal was also
(P = .006). In addition, 47% of patients with a tumor response
achieved their predetermined benefit goal, compared to only 15% of
nonresponders. These measurements are based exclusively on the
preselected goal and do not reflect other benefits that patients may
have received from treatment.
Side effects of cisplatin/epinephrine therapy were generally limited
to injection-site reactionsthe most common was pain. The
systemic side effects normally associated with systemic cisplatin
(Platinol) therapy were infrequent.
During early stages of the trials, four patients experienced
cerebrovascular side effects. However, none occurred after the
protocols were modified to exclude patients with tumors invading or
in close proximity to the carotid artery.
Individual Study Results
In the first study in 86 patients, conducted in North America, the
objective tumor response rate was 34% for cisplatin/epinephrine-treated
patients vs 0% for placebo (P = .001). The preselected
patient benefit was attained in 34% of the
cisplatin/epinephrine-treated patients vs 17% of the placebo-treated patients.
In the second study, which was conducted in 92 patients outside North
America, the objective tumor response rate was 25% for
cisplatin/epinephrine-treated patients vs 3% for placebo-treated
patients (P = .007). The preselected patient benefit was
attained in 19% of the cisplatin/epinephrine-treated patients vs 9%
of the placebo-treated patients.
In recent years, the FDA has increasingly looked at patient
benefit or quality-of-life measurements in addition to tumor response
rates in evaluating products, said Richard D. Leavitt, md,
senior vice president of Matrix. The combined results of these
studies showed statistically significant patient benefit attainment
with IntraDose therapy vs placebo, and the individual studies each
had a much higher proportion of patients who achieved the
treatment benefit goal in the IntraDose group than in the placebo group.
Dr. Leavitt added, Importantly, patients who exhibited a tumor
response were three times as likely to achieve their preselected
benefit goal as those who did not have a tumor response. These
results will strongly support an NDA filing for an indication in
recurrent or refractory head and neck cancer.