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The optimal dose of weekly docetaxel in combination with cisplatin and concomitant thoracic radiation therapy (XRT) in patients with locally advanced non-small cell lung cancer (NSCLC) is not well defined. The purpose of this study was to define the maximal tolerated dose (MTD) of docetaxel in this combination. Eligible patients had unresectable stage IIIA or IIIB NSCLC without pleural effusion. Treatment consisted of cisplatin 25 mg/m(2) plus docetaxel weekly and concomitant standard XRT for a total of 60 Gy at 200 cGy/fraction/day 5 times weekly for 6 weeks. The starting dose of docetaxel in the first cohort was 15 mg/m(2)/week. This dose was escalated by 5 mg/m(2) per cohort of 3 patients. No intrapatient dose escalation was allowed. The doses of cisplatin and XRT were not escalated. A total of 23 patients were enrolled, and 19 patients were evaluable for analysis. The first cohort (docetaxel 15 mg/m(2)/week) completed treatment without any Grade 3 or 4 toxicities. The second cohort (docetaxel 20 mg/m(2)/week) was expanded to 6 patients because of Grade 3 cough observed in 1 patient. One of 5 patients experienced Grade 3 esophagitis at the docetaxel 25 mg/m(2)/week dose level. Dose limiting toxicity consisting of Grade 3 esophagitis was reached in 4 of 5 patients receiving docetaxel at 30 mg/m(2)/week. This study determined the MTD of weekly docetaxel to be 25 mg/m(2) when combined with cisplatin 25 mg/m(2) and radiation therapy for locally advanced NSCLC. Further evaluation of this regimen in a phase II trial is underway.

Background. Colorectal cancer remains one of the most prevalent malignancies in the United States. Improvement in local disease control is seen when 5-fluorouracil (5-FU) is used in combination with pelvic irradiation for rectal adenocarcinoma. The frequent overexpression of insulin-like growth factor I receptor (IGF-I-R) in rectal adenocarcinoma suggests that inhibition of the signal transduction pathway may be a novel approach to enhance tumor response. This investigation seeks to define the role of IGF-I-R antagonism, using monoclonal antibody α-IR3, in augmenting cytotoxicity to adjuvant chemoradiation therapy for adenocarcinoma of the rectum. Materials and methods. SW 480 colon cancer cells were cultured to semiconfluent conditions with dose titrations performed for 5-FU to determine that the IC50 (inhibitory concentration of 50% of the cells) was 0.5 μg/ml. The IC50 for 5-FU was reassessed in the presence of IGF-I. Experimental groups included colon cancer cells combined with 5-FU; 6-MeV external beam radiation (100–500 cGy); and α-IR-3. Results. The addition of 100 ng/ml IGF-I 1 h prior to 5-FU or radiation significantly blunted the expected cytotoxicity, resulting in a 10-fold increase in the IC50 (from 0.5 to 5 μg/ml). Receptor antagonism using the monoclonal antibody α-IR-3 (100–400 ng/ml) produced a dose-dependent increase in cytotoxicity compared with 5-FU alone. The addition of radiation produced synergistic amplification of this response. Conclusions. IGF-I-R activation blocks the expected cytotoxic effects of 5-FU and external beam radiation. Receptor antagonism increased the cytotoxic response of chemoradiation therapy. These data suggest the utility of inhibiting IGF-I-R signal transduction in the treatment of rectal adenocarcinoma.

The objective of this study was to evaluate the acute tolerance to definitive external-beam radiation therapy (RT; EBRT) in patients with prostate adenocarcinoma and HIV and to review the published literature for this population. Three patients with prostate adenocarcinoma and HIV were treated with definitive RT. Medical records were reviewed for prostate cancer and HIV characteristics, RT details, and acute toxicity. A review of the published literature was performed for epidemiology, management, and outcome of these patients. All 3 patients had excellent acute tolerance to definitive EBRT and, with short follow-up, all had decreasing prostate-specific antigen levels. The published literature regarding patients with prostate adenocarcinoma and HIV is scarce but suggests that men with HIV might be at higher risk of developing prostate cancer. External-beam radiation therapy, brachytherapy, and surgery have all been used in the management of these patients. All 3 patients with prostate adenocarcinoma and HIV had an excellent acute tolerance to EBRT. Prostate cancer is expected to become an increasingly important health problem for men infected with HIV as their life expectancy lengthens.

7284 Background: In an effort to design easier and more convenient strategies for palliating advanced NSCLC locally as well as systemically, we conducted a dose escalation trial combining oral vino...

8186 Background: The use of phenytoin as primary seizure prophylaxis in patients with brain metastases from solid tumors is widely practiced at our institution, although this has fallen out of favo...