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| |  ASCO MEETING: Lutrin Safe, Effective For Recurrent Breast Cancer To The Chest Wall SUNNYVALE, CA -- May 17, 1999 -- Results from a phase II study reveals that Pharmacyclics, Inc.’s Lutrin(TM) photosensitiser shows activity in the photodynamic therapy (PDT) of patients with recurrent breast cancer to the chest wall. The study results were presented at the meeting of the American Society of Clinical Oncology (ASCO) in Atlanta. The phase II study was designed to evaluate the safety, tolerability and efficacy of Lutrin photosensitiser for PDT in women with recurrent breast cancer to the chest wall, which failed previous chemotherapy and radiation therapy. Fifty-seven treatment courses were given to 52 patients with advanced refractory disease. Eighty-two percent of these patients had failed three or more chemotherapy regimens and all the patients had recurrence or persistence of tumour following radiation therapy to the chest wall. The study evaluated the administration of different doses of Lutrin, followed by illumination of the chest wall with light delivered at either three hours, six hours, 24 hours, 48 hours, 72 hours or 96 hours after intravenous injection of the drug. Each patient, in the 11 cohorts tested, received illumination with light to large areas of the chest wall (up to 240 cm2) encompassing both the tumour and adjacent uninvolved skin. The purpose of the study was to identify treatment regimens that demonstrated anti-tumour activity with an acceptable level of treatment-related adverse events. Tumour response was determined using an investigator's global assessment, which was based on physical examinations and photographs of the chest wall disease. All lesions within the treatment field were evaluated and an overall assessment of efficacy was made for each patient. Tumour responses were seen in 64 percent of patients. In 42 percent of patients, the global assessment following treatment indicated that tumours were either not detectable (20 percent) or had obvious significant decrease evident on physical examination or photographs (22 percent). Safety and tolerability appeared to be dependent on both drug dose and the time interval between Lutrin administration and illumination of the chest wall with light. Patients receiving chest wall illumination 24 hours or more, following intravenous administration of Lutrin, experienced pain that was manageable with standard analgesics. Pain was more severe in patients treated with light given at shorter intervals, sometimes requiring conscious sedation. Cutaneous toxicity, including eschar formation or necrosis, was seen in the skin overlying the tumours in 11 of 39 patients treated with light at time intervals less than 24 hours. Only two of 18 patients receiving light illumination 24 hours or more after receiving Lutrin experienced this toxicity. Cutaneous toxicity was limited to the tumour-involved areas of skin except in patients receiving the highest doses of Lutrin followed by photoillumination given at the shortest intervals. "We are impressed by the tumour selectivity and responses seen in this extremely refractory group of breast cancer patients," stated T. Jeffery Wieman, M.D., professor of surgical oncology at the University of Louisville and principal investigator of the study. "We are seeing important clinical benefits from this treatment in women who have exhausted all other standard therapeutic options." Lutrin is a lutetium-texaphyrin molecule that is activated by a wavelength of light that is capable of penetrating deeply through tissues and blood. Lutrin is cleared relatively quickly from the blood and normal tissues but accumulates in tumours providing the potential to selectively treat large tumours with reduced damage to adjacent normal tissues. In previous studies, significant pain and skin reactions in the illuminated field were seen in patients with recurrent breast cancer receiving photoillumination of large areas of the chest wall within three hours of administration of Lutrin. The data presented at ASCO indicate that increasing the interval between drug and light administration provides greater tumour selectivity and less toxicity to adjacent normal skin. Breast cancer frequently recurs in the skin and soft tissues of the chest wall following primary treatment. These tumours usually involve relatively large areas of the chest wall where they may form large tumours, numerous small nodules or infiltrating sheets of cells. When not adequately controlled, these tumours may grow progressively causing pain, ulceration, necrosis and serious infections of the skin. Moreover, women suffer psychological complications associated with visible and readily apparent tumour growth. Recurrent breast cancer to the chest wall is treated with chemotherapy and radiation therapy to the chest wall region. About half of the patients will not experience adequate tumour control with these therapies. In these patients, the tissues of the chest wall are severely compromised and deformed as a result of radiation exposure and tumour infiltration. PDT has been used experimentally to treat recurrent breast cancers to the chest wall. This approach has been hindered by the lack of tumour selectivity of existing photosensitisers, restricting treatment to individual tumour nodules or very small areas of the chest wall. This has limited clinical utility because these tumours usually involve large areas of skin and soft tissues of the chest wall. Also, contiguous uninvolved skin is at high risk for recurrence and must be included in the treatment field to reduce the risk of subsequent recurrences.
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