Long-term follow-up on National Cancer Institute Phase I/II study of glioblastoma multiforme treated with iododeoxyuridine and hyperfractionated irradiation.

PURPOSE: We report the results of the final phase I/II program in glioblastoma (GBM) multiforme patients using only hyperfractionated irradiation and intravenous iododeoxyuridine (IdUrd). METHODS: For a decade we investigated halogenated pyrimidine radiosensitizers in an effort to exploit the potential for differential uptake of thymidine analogs between proliferating tumor and normal brain tissues. Trials began with bromodeoxyuridine (BrdUrd) but were changed to IdUrd when the latter proved less photosensitizing. A series of dose-escalating pilot trials led to treatment at a maximum-tolerated dose (MTD) of IdUrd of 1,000 mg/m2/d for two separate 14-day courses, one during the initial radiation field and one during the cone down. The radiotherapy also evolved over time and was hyperfractionated in all cases reported. Over 5 years we accrued 45 patients into the final hyperfractionated, 1,000 mg/m2/d scheme. We report here results on only the patients with minimum follow-up of 1 year (90% had at least 2 years of follow-up) or until death. RESULTS: The results do not indicate a significant benefit for use of sensitizers, as compared with other contemporary and aggressive types of radiation treatment. The median survival has been 11 months, with a 2-year actuarial survival of 9%. As yet, there are no survivors at 3 years. Tumor biopsies at craniotomy showed relatively low sensitizer incorporation. CONCLUSION: The failure of radiosensitizers combined with radiation therapy to show major benefit may be due to patient selection but appears also to be related to the combined problems of poor drug penetration/uptake into tumor, tumor-cell heterogeneity, and a high inherent cellular radioresistance of GBM.

Photodynamic therapy: the NCI experience and its nursing implications.

Recent laboratory and clinical data have demonstrated encouraging results with a new treatment modality, photodynamic therapy (PDT). Initially used as a technique for tumor localization, PDT produces cytotoxic effects in superficial tumors such as those growing on the surfaces of the bladder, pleura, head and neck, bronchus, chest wall, and peritoneal cavity. PDT has three components: a light-sensitizing drug, light (generally from a laser), and oxygen. Initial results of phase I clinical trials conducted at the National Cancer Institute (NCI) are encouraging, and systemic toxicities have been minimal. Nursing intervention includes teaching, counseling, monitoring acute reactions, and follow-up care of these patients. This study outlines the results of experience with PDT at NCI and the nursing implications.

Photodynamic therapy for chest wall recurrence in breast cancer.

Photodynamic therapy is the use of a sensitizer (dihematoporphyrin ethers) which is preferentially retained in tumor cells and activated by subsequent light delivery resulting in a selective tumoricidal effect. Between 1986 and 1989, we treated 20 patients with photodynamic therapy for chest wall recurrence of breast cancer. Responses were seen (20% complete response, 45% partial response, 35% no response), but the duration of response was short (average 2.5 months). Complications, in decreasing frequency, included pain, ecchymoses, blistering, ulceration and necrosis in the area of tumor involvement on the chest wall. One patient required skin flap reconstruction for full thickness necrosis. A limitation to this mode of therapy is that the sensitizer currently used is activated by light at a wavelength of 630 nm. This light can penetrate to a tissue depth of only 0.5 to 1.0 cm; thus, deeper disease cannot be treated. Future research must focus on the development of a clinically useful photosensitizer that can be activated by light at longer wavelengths and thereby achieve deeper tissue penetration. This would greatly expand the patient population for which this therapy is useful.