Biomedical subjects

T Smudzin

Publications and source records attributed to T Smudzin.

3 recordsLinked to original sources

PubMed2001

Circulating IL-6 as a predictor of radiation pneumonitis.

PURPOSE: We report results from a clinical research protocol investigating circulating pro-inflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNFalpha]) in relation to radiation pulmonary injury. METHODS AND MATERIALS: In a protocol for cytokine measurement, 25 patients had clinical follow-up longer than 12 months, and 24 had serial cytokine data. Serial plasma specimens before, during, and after thoracic radiotherapy were analyzed for IL-6 and TNFalpha using enzyme-linked immunosorbent assay (ELISA). Radiation pulmonary injury was defined using National Cancer Institute Common Toxicity Criteria. RESULTS: Of the 24 patients, 6 had Grade 1 pneumonitis, and 13 had Grade 2 pneumonitis. There was no Grade 3/4 pneumonitis. Median time of radiation pneumonitis was between 8 and 12 weeks post-therapy. IL-6 levels before, during, and after thoracic radiation therapy were significantly higher in those who developed pneumonitis. In contrast, we did not detect a significant correlation between plasma TNFalpha and radiation pneumonitis. CONCLUSIONS: High pretreatment plasma levels of IL-6 predisposed patients to the risk of radiation pneumonitis. Pretreatment IL-6 level may serve as a predictor for radiation pneumonitis. Serial plasma IL-6 was consistently higher for the pneumonitis group. The role of IL-6 in the cytokine cascades that promote radiation pulmonary injury deserves further investigation.

Adult↗

PubMed2001

Schedule-dependent pulsed paclitaxel radiosensitization for thoracic malignancy.

The objective of this study was to apply preclinical research of paclitaxel radiosensitization to the treatment of thoracic malignancy. Human lung cancer cell line NCI520 and epidermoid cell line A431 were investigated in vitro for radiosensitizing effects of paclitaxel. Optimal schedule of paclitaxel treatment was applied to a clinical protocol as well as off-protocol treatment of thoracic malignancy. Pulsed paclitaxel with concurrent once-daily radiation was delivered every 48 hours during the week using doses of 15 mg/m2, 20 mg/m2, or 25 mg/m2 in a phase I clinical trial of dose escalation. Preclinical data support the finding that low-dose paclitaxel is sufficient for radiosensitization. Data also support that delaying radiation is better than immediate radiation after drug treatment. Twenty-three patients have enrolled in the phase I clinical trial. Seventeen patients completed treatment (6 at 15 mg/m2; 5 at 20 mg/m2; and 6 at 25 mg/m2). Mean tumor shrinkage at 4 to 6 weeks after therapy was 82%, 84%, and 84% for dose levels I, II, and III, respectively [average primary tumor shrinkage was 83% +/- 8% (95% C.I.)]. Locoregional tumor response rate was 100% [12% (2/17) complete response and 88% (15/17) partial response] with low rates of toxicity. It is concluded that pulsed low-dose paclitaxel and radiation is a very effective and well-tolerated regimen for thoracic malignancy.

Adult↗

PubMed1994

Preliminary results of a pilot study using WR-2721 before fractionated irradiation of the head and neck to reduce salivary gland dysfunction.

PURPOSE: Based on in vivo evidence of radioprotection of the salivary glands using WR-2721, a pilot study was undertaken to determine the feasibility, toxicity, and salivary function of patients receiving WR-2721, while undergoing radiation therapy to the head and neck. METHODS AND MATERIALS: Patients undergoing radiation therapy for cancer of the head and neck were eligible if the major salivary glands received more than 45 Gy. WR-2721 was administered over 6 min IV, 10-15 min prior to each dose of radiation five times per week. Saliva was collected and measured prior to radiation therapy, weekly during radiation therapy, 1 month postradiation therapy, and every 3 months thereafter. Flow rates of unstimulated whole saliva, stimulated whole saliva, and stimulated parotid saliva were measured using standard techniques. 99mTc salivary scintiscans were performed prior to radiation therapy, 1 month postradiation therapy and every 3 months thereafter. Nine patients are presently enrolled on the first dose level (100 mg/m2) of this study. Eight completed per protocol, two with minor decreases of total WR-2721 doses. Two patients progressed with distant metastases soon after completion of therapy. All available data are included in the analysis. Median follow-up for all patients is 18 months. RESULTS: Flow rates of unstimulated whole saliva decreased significantly during radiation therapy reaching 5.6% of baseline at 9 months postradiation therapy, subsequently recovering to 20% of baseline, then remaining stable over time. Stimulated whole salivary flow rate similarly decreased during radiation therapy and reached its nadir (11% of baseline) at 3 months postradiation therapy, improving to 27% of baseline by 2 years. The stimulated parotid flow rate decreased during radiation therapy to 1.4% of pretreatment levels. Significant recovery took place 6 months postradiation therapy and by 18 months values had recovered to 54% of baseline. 99mTc salivary scintiscans confirmed this rebound of parotid function postradiation therapy. Toxicity was minimal with the exception of one patient who received only 27% of the planned total drug dose due to grade 3 hypotension after the eighth treatment. No recovery of salivary function has been seen in this patient; flow rates remain zero in all three areas tested 21 months after radiation. CONCLUSIONS: Administration of WR-2721 prior to each dose of radiation was feasible and without significant toxicity at 100 mg/m2. Salivary gland function improved over time after completion of radiation, particularly the parotid. Future directions include escalation of WR-2721 dose to 200 mg/m2 and then 300 mg/m2, and a Phase III randomized trial will be undertaken once the optimal dose is established.

Amifostine↗