By Mary Welch
Matrix Pharmaceutical Inc.'s preliminary Phase III data for IntraDose showed positive tumor response in patients with advanced breast cancer and malignant melanoma, and the company now is aiming to hook up with a partner by the end of the year to market the product.
To date, the trial has evaluated 24 melanoma patients and 28 patients with breast cancer. All had prior therapies such as surgery, radiotherapy and systemic chemotherapy.
"These patients basically are terminal. They have run the gamut of traditional therapies for these tumors and the prognosis is poor," said Peter Dworkin, senior director of investor relations and corporate communications for the Fremont, Calif., company. "Our endpoints are not curative; rather, they are palliative, or prolonging a better quality of life."
The endpoints are objective tumor responses, particularly in the tumor selected by the physician as the most troublesome, and achieving palliative and preventive treatment goals, again chosen by the doctor.
Each patient had IntraDose injected directly into the tumor. Patients receive up to six weekly injections of IntraDose and then are observed weekly for four weeks. IntraDose contains a proprietary collagen-based gel, which provides for flow relief and long retention of the cisplatin within the tumor; epinephrine, a vasoconstrictor; and cisplatin, a widely used, platinum-containing chemotherapy drug. Because it is put directly into the tumor, IntraDose delivers a higher concentration of cisplatin than could be done with regular chemotherapy and yields fewer side effects.
Among the 28 patients treated to date with recurrent breast cancer, the preliminary data showed nine patients (32 percent) had either a complete response (100 percent reduction of tumor volume) or a partial response (50 percent or greater reduction) in their most troublesome tumor for 28 days. Another five experienced tumor shrinkage of at least 50 percent in the problem tumor but, for various medical reasons, were not followed for the 28 days required to be included in the partial-response tally. In all, the 28 patients had a total of 86 tumors, 22 of which responded to treatment with IntraDose. The trials are open-label, single-arm studies.
Formulation Alleviates Side Effects
The reports were presented yesterday at the tenth annual symposium on New Drugs in Cancer Therapy, in Amsterdam, jointly sponsored by the National Cancer Institute of the National Institutes of Health, of Bethesda, Md., and the European Organization for Research and Treatment of Cancer, headquartered in Amsterdam.
In the preliminary data on the 24 malignant melanoma patients, who had a total of 117 tumors, research found that four patients — or 17 percent — had responses in their most troublesome tumors and eight achieved the physician-selected goal. Twenty-seven of the 117 treated melanomas had objective tumor responses.
"We'll get the bulk of the data later this year," said Dworkin. "But the results show that IntraDose substantially reduces tumor volume and achieves the physician-selected goals. Those goals can be a number of factors — pain control, wound care, preventing the tumor from invading vital organs or blood vessels. Remember, these are not curative goals."
In addition, the treatments were generally well-tolerated, with none of the kidney, neurological or hearing-related problems usually associated with intravenous cisplatin therapy. Common side effects of systemic cisplatin treatments, such as vomiting and nausea, were noted less frequently following IntraDose injections.
While the studies on breast cancer and melanoma patients should be finished by the end of the year, the two double-blind, placebo-controlled studies in patients with advanced head and neck tumors have run into some enrollment delays. The problem is that a larger sample size is needed and the company is having difficulty finding patients with late-stage cancer. Plus, after consulting with the FDA, Matrix decided to exclude patients with neck tumors close to the carotid artery, who are susceptible to strokes and other serious neurological problems.
Matrix expects to finish all four trials by the end of 1999 and file a marketing application in 2000.
Currently IntraDose is in Phase II trials in primary liver cancer and colorectal cancer metastatic to the liver. Encouraging preliminary results allowed the company to extend enrollment.
Matrix's stock (NASDAQ:MATX) closed at $4.687, up $0.125. *