Biomedical subjects

H Choy

Publications and source records attributed to H Choy.

At least 55 records · Page 3Linked to original sources

PubMed1999

The role of UFT in combined-modality therapy.

Fluorinated pyrimidines have long been used as radiosensitizers in combined-modality therapy for solid tumors. Nonetheless, the most commonly used drug, 5-fluorouracil (5-FU), is inconvenient to administer, particularly when given by continuous intravenous infusion. Continuous infusion 5-FU does offer a survival advantage over bolus in the treatment of large bowel tumors. This holds true regardless of whether radiation therapy is concomitantly given. UFT, a combination of uracil and tegafur (in a molar ratio of 4:1), is an attractive alternative. Trials to date suggest at least chemotherapeutic equivalence compared to 5-fluorouracil, and UFT is much simpler to administer. UFT is administered orally and can safely be combined with oral leucovorin. There is profound scientific rationale for using UFT with radiation therapy, and early trials in gastrointestinal malignancies demonstrate the safety and efficacy of the combination. Further studies will determine the optimal timing and uses for concomitant UFT and radiation therapy.

Administration, Oral↗

PubMed1999

Concurrent chemotherapy and radiotherapy in patients with brain tumors.

Because treatment for most brain tumors remains inadequate, there has been a sustained interest in using concurrent chemotherapy and radiotherapy to improve local control, prolong overall survival, and reduce treatment-related toxicity. Unfortunately, many currently available radiosensitizers are either ineffective against brain tumors or have a reduced ability to cross the blood-brain barrier when administered systemically. Many agents also have overlapping toxicities with cranial irradiation or enhance the toxicity of radiation in a way that potentially compromises care. Finally, the addition of chemotherapy to cranial irradiation complicates the assessment of tumor response. Despite these barriers, trials with a number of promising agents are currently under way. These trials have already provided crucial insights into the pharmacokinetics, clinical pharmacology, and practical management of brain tumor patients with concurrent chemotherapy and radiotherapy. These findings should rapidly lead to the safer and more effective use of combined-modality therapy in patients with central nervous system cancer.

Animals↗

PubMed1999

The role of radiation, with or without chemotherapy, in the management of NSCLC.

Lung cancer is the leading cause of cancer death in the United States. Surgery is the treatment of choice for early stage patients. Despite radical surgery, patients with early stage lung cancer remain at risk for recurrence. The role of adjuvant therapy remains to be clearly defined. Locally advanced non-small-cell lung cancer is too extensive for surgical resection, yet does not show evidence of metastatic disease. Historically, these patients were treated with radiation alone. More recent studies have provided the rationale for combining radiation with chemotherapy for patients with good performance status who have locally advanced disease. For patients with marginally resectable tumors, treatment is often given preoperatively (neoadjuvant) as a means of shrinking the tumor to make it resectable. In patients with clearly unresectable disease, radiation with chemotherapy has been established as better than either modality alone. Palliative radiation alone can be used for patients who cannot tolerate this aggressive approach. The optimal sequencing, as well as the best chemotherapeutic agent to use, remains under investigation. Some of the newer agents showing promise in the treatment of non-small-cell lung cancer include paclitaxel (Taxol) and carboplatin (Paraplatin). Other agents that are currently under investigation include topotecan, gemcitabine, and vinorelbine (Navelbine).

Antineoplastic Agents↗

PubMed1999

Combined chemoradiation therapy for limited-stage small-cell lung cancer.

After nearly 4 decades of use in treating small-cell lung cancer (SCLC), thoracic radiation has become integral to the management of limited-stage disease. Many prospective randomized trials have demonstrated that adding thoracic radiation therapy to chemotherapy improves locoregional control and survival at 3 and 5 years. This has resulted in a greater appreciation of the role of thoracic radiation in the treatment of SCLC. Currently, the most commonly used regimens incorporate concurrent administration of cisplatin (Platinol) and etoposide (VePesid) chemotherapy and radiation doses of 45 Gy given over 5 weeks. However, issues concerning timing, volume, and dose fractionation remain to be resolved.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Prognosis of adenocarcinoma arising in Barrett's esophagus.

BACKGROUND: The rising incidence of adenocarcinoma of the esophagus, as well as its association with Barrett's esophagus, has been reported previously. We report our experience in treating patients with adenocarcinoma arising in Barrett's esophagus. METHODS: A retrospective review was performed of 70 consecutive patients with adenocarcinoma of the esophagus treated between November 1988 and April 1996 with preoperative chemoradiation and resection. Demographics, pathologic features, and survival were compared with patients who developed adenocarcinoma of the esophagus without Barrett's. Statistical analyses was performed using Student's t test, Fisher's exact test, and Kaplan-Meier where appropriate. RESULTS: Thirty-two (46%) patients had adenocarcinoma arising in Barrett's esophagus. During the last 4 years, 72% (23 of 32) of patients with adenocarcinoma had coexistent Barrett's. No differences in patients with or without Barrett's with regard to age, sex, race, tumor location, preoperative chemotherapy, type of operation, or operative stage were observed. Tumors in patients with Barrett's were larger (p = 0.017), had better differentiation (p = 0.002), and were less likely to have a complete response to preoperative chemoradiation (p = 0.05). Actuarial survival, however, was better in the group with associated Barrett's esophagus (p = 0.033). CONCLUSIONS: The incidence of adenocarcinoma of the esophagus arising in Barrett's esophagus appears to be increasing. It may be distinct clinically and biologically from adenocarcinoma of the esophagus that does not develop in association with Barrett's epithelium. Long-term survival was better in our patients with adenocarcinoma associated with Barrett's esophagus.

Adenocarcinoma↗

PubMed1998

Histologic evidence of a radiosensitizing effect of Taxol in patients with astrocytomas.

The new anticancer agent Taxol appears to potentiate the effects of radiation on brain tumor cell lines in vitro and was recently evaluated by our group as a radiosensitizer in a phase I study for primary brain tumors. In that study, we administered Taxol as a three-hour IV infusion repeated every week for six weeks and gave daily cranial irradiation concurrently for a total of 6000 rads. We reviewed the charts of the 60 patients who participated in the study, and identified twelve patients who underwent a second surgery after treatment because of progressive symptoms and an enlarging intracranial mass on MRI. Pathologically, each patient showed prominent radionecrosis, and other evidence of accelerated radiation changes (confluent areas of coagulative necrosis, bizarre nuclei, marked thickening and fibrinoid changes in multiple blood vessels). These changes were noted many weeks earlier than would be expected after radiation therapy alone and were independent of age, and tumor histology. We postulate that the accelerated radiation changes may be due to the radiation sensitizing effects of Taxol. We also noted a change of the pattern of tumor recurrence, compared to historic reports, and a dose-necrosis relationship where the resected tumor is formed completely of necrotic tissue in patients who received 150 mg/m2 or higher dose of Taxol. These observations may be of significance for future study design.

Adult↗

PubMed1998

Phase I trial of weekly paclitaxel in advanced lung cancer.

PURPOSE: We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose (MTD) of paclitaxel using an extended weekly schedule. PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/microL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended first-cycle dose. RESULTS: Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle 1. Neutropenia was dose-limiting. Fourteen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35% +/- 10%) patients demonstrated an objective response. CONCLUSION: The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

Adult↗

PubMed1998

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer.

PURPOSE: Combined modality therapy for non-small-cell lung cancer (NSCLC) has produced promising results. A multiinstitutional phase II clinical trial was conducted to evaluate the activity and toxicity of paclitaxel, carboplatin, and concurrent radiation therapy on patients with locally advanced NSCLC. PATIENTS AND METHODS: Forty previously untreated patients with inoperable locally advanced NSCLC entered onto a phase II study from March 1995 to December 1996. On an outpatient basis for 7 weeks, patients received paclitaxel 50 mg/m2 weekly over 1 hour; carboplatin at (area under the curve) AUC 2 weekly; and radiation therapy of 66 Gy in 33 fractions. After chemoradiation therapy, patients received an additional two cycles of paclitaxel 200 mg/m2 over 3 hours and carboplatin at AUC 6 every 3 weeks. RESULTS: Thirty-nine patients were eligible for the study. The survival rates at 12 months were 56.3%, and at 24 months, 38.3%, with a median overall survival of 20.5 months. The progression-free survival rates at 12 months were 43.6%, and at 24 months, 34.7%, with a median progression-free survival of 9.0 months. Two patients did not receive more than 2 weeks of concurrent chemoradiotherapy and were not assessable for toxicity and response. The overall response rate (partial plus complete response) of 37 assessable patients was 75.7%. The major toxicity was esophagitis. Seventeen patients (46%) developed grade 3 or 4 esophagitis. However, only two patients developed late esophageal toxicity with stricture at 3 and 6 months posttreatment. CONCLUSION: Combined modality therapy with paclitaxel, carboplatin, and radiation is a promising treatment for locally advanced NSCLC that has a high response rate and acceptable toxicity and survival rates. A randomized trial will be necessary to fully evaluate the usefulness of these findings.

Adult↗

PubMed1998

Paclitaxel, carboplatin and radiation therapy for non-small-cell lung cancer.

Preclinically, the taxanes appear to potentiate radiation more effectively than do the platinum compounds. In our phase I trial (LUN-17) in patients with advanced non-small-cell lung cancer, we defined the maximum tolerated dose and toxicity profile of concomitant radiation and paclitaxel (Taxol). We then conducted a series of phase II clinical trials in patients with stage III A or stage III B non-small-cell lung cancer to explore the role of paclitaxel in a combined-modality approach; these trials were based on the very low paclitaxel concentrations needed to enhance radiation in the phase I trial and the relatively high response rate achieved. Our LUN-27 trial of weekly paclitaxel and concurrent radiation for 6 weeks with no adjuvant chemotherapy produced substantial response and survival rates with acceptable toxicity. LUN-56 added weekly carboplatin (Paraplatin) during the initial concurrent phase as well as two cycles of standard-dose paclitaxel and carboplatin. The ongoing LUN-63 phase II study delivers concurrent weekly paclitaxel and carboplatin with hyperfractionated radiation, followed by two cycles of adjuvant paclitaxel and carboplatin, to further improve local control and overall survival. We are currently extending the investigation of concurrent weekly paclitaxel plus radiation in a large-scale, three-arm, randomized phase II trial. To date, toxicity in all trials has been acceptable and compares favorably with other regimens. The major side effect, esophagitis, occurs predictably and is managed easily, abating shortly after therapy is completed. The rates of overall response and 1- and 2-year survival are very encouraging, and phase III evaluation is warranted.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Phase II trial of weekly paclitaxel and concurrent radiation therapy for locally advanced non-small cell lung cancer.

We conducted a prospective Phase II study to determine the response rate, toxicity, and 2-year survival rate of concurrent weekly paclitaxel and radiation therapy (RT) for locally advanced unresectable non-small cell lung cancer. The weekly paclitaxel regimen was designed to optimize the radiosensitizing properties of paclitaxel. Thirty-three patients with unresectable stage IIIA and IIIB non-small cell lung cancer from six institutions were entered into the study between March 1994 and February 1995. Weekly i.v. paclitaxel (60 mg/m2; 3-h infusion) plus concurrent chest RT (60 Gy over 6 weeks) was delivered for 6 weeks. Twenty-nine patients were evaluable for response. Three patients achieved a complete response (10%), and 22 patients (76%) achieved a partial response, for an overall response rate of 86% (95% confidence interval, 68-96%). One patient progressed during the therapy, and three patients had stable disease. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 11 patients (37%). One patient died of pneumonia after completion of therapy. Additional grade > or =3 toxicities included pneumonitis (12%) and neutropenia (6%). One patient had a grade 3 hypersensitivity reaction. The median overall survival duration for all 33 patients who entered the study was 20 months, and 1-, 2-, and 3-year overall survival rates were 60.6%, 33.3%, and 18.2%, respectively. The median progression-free survival duration for all 33 patients was 10.7 months, and 1-, 2-, and 3-year progression-free survival rates were 39.4%, 12.1%, and 6.1%, respectively. Weekly paclitaxel plus concurrent RT is a well-tolerated outpatient regimen. The survival outcome from this regimen is encouraging and seems to be at least equivalent to that of other chemotherapy/radiation trials. These findings warrant further clinical evaluation of weekly paclitaxel/RT in Phase II trials in the neoadjuvant setting and in combination with other cytotoxic agents.

Adult↗

PubMed1997

Paclitaxel and concurrent radiation for locally advanced pancreatic and gastric cancer: a phase I study.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and potential antitumor activity of weekly paclitaxel with concurrent radiation (RT) for locally advanced pancreatic and gastric cancer. PATIENTS AND METHODS: Thirty-four patients with locally advanced adenocarcinoma of the pancreas or stomach were studied. The initial dose of paclitaxel was 30 mg/m2 by 3-hour intravenous (I.V.) infusion repeated every week for 6 weeks with 50 Gy RT. Doses were escalated at 10-mg/m2 increments in successive cohorts of three new patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m2/wk were abdominal pain within the RT field, nausea, and anorexia. Of 23 patients with assessable disease, 11 (seven with gastric, four with pancreatic cancer) had objective responses for an overall response rate of 48%. CONCLUSION: Concurrent paclitaxel with upper abdominal RT is well tolerated at dosages that have substantial activity. A phase II trial of neoadjuvant paclitaxel and RT at the MTD of 50 mg/m2/wk is underway.

Adult↗

PubMed1997

Prophylactic cranial irradiation in small cell lung cancer: rationale, results, and recommendations.

The utility of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) constitutes one of the longest running debates in oncology. Despite dozens of prospective and retrospective studies and decades of individual experience, a consensus has been reached on only two issues: (1) when administered to all patients with SCLC, PCI decreases the likelihood of developing brain metastases by about half, but (2) PCI does not significantly prolong survival. Uncertainty persists over many critical questions, including whether, when, and how to administer PCI; whether identifiable subgroups of patients benefit more tangibly from PCI; how frequent and severe the long-term side effects of PCI are; whether withholding treatment until brain metastases are diagnosed is clinically responsible and cost effective; and how newer forms of treatment for brain metastases should be integrated into the picture. In this review, we discuss the epidemiology and natural history of brain metastases in patients with SCLC, the results of studies examining the efficacy of PCI, data on the early and late toxicities of PCI, and the status of alternative therapies for patients with brain metastases from SCLC. Based on this information, an approach to newly diagnosed patients is suggested, and recommendations for future study are made.

Brain Neoplasms↗

PubMed1997

Weekly paclitaxel in patients with advanced lung cancer: preliminary data from a phase II trial.

We conducted a phase II trial in chemotherapy-naive patients with advanced non-small cell lung cancer to determine the efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) delivered at a maximum tolerated dose of 175 mg/m2 on an extended weekly schedule. Patients with stage IIIB/IV non-small cell lung cancer were eligible if they had an Eastern Cooperative Oncology Group performance status of 0 to 2, had received no previous chemotherapy, demonstrated normal hematologic and hepatic function, and could provide informed consent. Paclitaxel 175 mg/m2 was administered as an intravenous infusion weekly over 3 hours with standard premedication, for 6 weeks of an 8-week cycle. Doses were modified for absolute neutrophil count less than 1.5 x 10(9)/L or neuropathy greater than grade I on the day of therapy. Patients without progressive disease received subsequent cycles at the same dose. To date, 30 patients have been enrolled; data are available for 25. The median age was 65 years (range, 38 to 78 years), 23 patients were performance status 0 or 1, and 14 had received prior radiation. Sites of disease included the lung (23 patients), central nervous system (11), bone (seven), liver (one), kidney (one), and soft tissue (eight). Eighty-three percent, 75%, 58%, and 50% of intended doses were delivered during cycles 1 though 4, respectively. Grade 2/3 neuropathy occurred in nine patients, but improved in all nine following dose reduction. Grade 3/4 neutropenia occurred in 10 patients. Partial responses occurred in 14 of 25 patients (56%; 95% confidence interval, 46% to 66%). Median duration of response was 6.5 months, and the 1-year survival rate was 53%. The extended weekly paclitaxel schedule results in enhanced dose intensity, marked activity, and acceptable toxicity. Paclitaxel given weekly at maximum dose intensity may be more effective than conventional paclitaxel administration schedules.

Adult↗

PubMed1997

Preliminary analysis of a phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small cell lung cancer.

We conducted a prospective phase II study to determine the response rate, toxicity profile, and survival rate among patients with locally advanced unresectable non-small cell lung cancer receiving concurrent weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), carboplatin, and hyperfractionated radiation therapy followed by two cycles of adjuvant paclitaxel and carboplatin. The weekly paclitaxel/carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. Thirty-two patients with unresectable stage IIIA and IIIB non-small cell lung cancer from Vanderbilt Cancer Center Affiliate Network institutions entered the study from June 1996 until February 1997. Weekly intravenous paclitaxel (50 mg/m2 over 1 hour) and weekly carboplatin (area under the concentration-time curve of 2) plus concurrent hyperfractionated chest radiotherapy (1.2 Gy twice daily [69.6 Gy total]) delivered for 6 weeks were followed by two cycles of paclitaxel (200 mg/m2) and carboplatin (area under the concentration-time curve of 6). Among 22 patients evaluable for response, one (4.5%) achieved a complete response and 16 (72.7%) achieved partial response, for an overall response rate of 77%. Among 23 patients evaluable for toxicity, esophagitis was the principal finding: grade 3 or 4 esophagitis occurred in eight patients (35%). Grade 3 and 4 pulmonary toxicities each occurred in 26% of patients. Thus, weekly paclitaxel/carboplatin plus concurrent hyperfractionated radiotherapy is a well-tolerated outpatient regimen with an encouraging response rate that is at least equivalent to more toxic chemoradiation regimens. These findings indicate that further clinical evaluation of weekly paclitaxel/carboplatin/hyperfractionated radiotherapy is warranted in phase III trials.

Adult↗

PubMed1996

p53 mutations do not predict response to paclitaxel/radiation for nonsmall cell lung carcinoma.

BACKGROUND: Mutations in the tumor suppressor gene p53 have been associated with resistance to ionizing radiation and chemotherapy. Paclitaxel and concurrent radiation (paclitaxel/RT) achieve high response rates with locally advanced nonsmall cell lung carcinoma (NSCLC). In vitro data and animal studies suggest that paclitaxel may have a unique ability to activate tumor cell apoptosis in the absence of wild-type p53 function. The authors sought to determine whether p53 mutations affect response to paclitaxel/RT in patients with locally advanced NSCLC. METHODS: Thirty patients with Stage IIIA or IIIB NSCLC who participated in Brown University Oncology Group protocols utilizing paclitaxel/RT had tumor tissue that was adequate for analysis. Mutations were detected in tumor tissue by single-strand conformation polymorphism analysis of exons 5 through 8 of the p53 gene, and confirmed by direct sequencing. RESULTS: Mutations in p53 were found in 12 of 30 patients (40%). The response rates (complete plus partial) of 75% for patients with tumors with p53 mutations, and 83% for patients with wild-type p53, did not differ significantly (P = 0.70). CONCLUSIONS: p53 mutations do not predict response of patients with NSCLC to paclitaxel/RT. This finding is in striking contrast to results with other chemotherapeutic agents and ionizing radiation. These clinical data support in vitro data and animal studies regarding the unique mechanism of the action of paclitaxel. Further investigation is needed to determine the mechanism of lung tumor cell death after paclitaxel/RT. These results suggest that paclitaxel/RT may be an active regimen for patients with other locally advanced neoplasms with high rates of p53 gene mutations.

Aged↗

PubMed1996

Concurrent Paclitaxel and Radiation Therapy for Solid Tumors.

BACKGROUND: Combination radiation and chemotherapy has an intuitive appeal for improving cancer treatment. Experimental results suggest that paclitaxel plus radiation might produce additive or synergistic effects. METHODS: A series of phase I and II trials to test tolerance and begin to evaluate effectiveness were performed on patients with non-small cell lung cancer, high-grade astrocytic brain tumors, and pancreatic and gastric cancers. RESULTS: Tolerance of the combined drug and radiation programs was generally good. Esophagitis was dose-limiting for the intrathoracic tumors. Hematologic toxicity was mild, but peripheral neuritis and cutaneous reactions were common. CONCLUSIONS: These trials show that paclitaxel plus concurrent radiation is feasible at the dose levels and schedules tested. Antitumor responses have been observed.

Journal Article↗

PubMed1996

Phase I study of weekly outpatient paclitaxel and concurrent cranial irradiation in adults with astrocytomas.

PURPOSE: Astrocytomas are extremely resistant to currently available treatments. Cranial irradiation is a mainstay of frontline therapy, but tumor recurrence is nearly universal. Paclitaxel has shown antitumor efficacy against astrocytoma cell lines, and is a potent radiosensitizer. For these reasons, we conducted a phase I study of weekly paclitaxel and concurrent cranial irradiation in patients with newly diagnosed astrocytomas. PATIENTS AND METHODS: Patients with astrocytomas were eligible for this study following initial surgery if they had a Karnofsky performance score (KPS) > or = 60%; normal hematologic, liver, and renal function; and could give informed consent. Beginning on day 1 of treatment, patients received paclitaxel by 3-hour infusion once weekly for 6 weeks, concurrent with standard cranial irradiation. Pharmacokinetic studies were performed on 10 patients. RESULTS: Sixty patients were enrolled; 56 were fully assessable. Forty-eight had glioblastomas (GBMs), 10 anaplastic astrocytomas (AAs), and two astrocytomas. Age ranged from 21 to 81 years (median, 55); KPS ranged from 60 to 100 (median, 70). The paclitaxel dose was escalated from 20 mg/m2 to 275 mg/m2. No clinically significant anemia or thrombocytopenia occurred. Only one patient (175 mg/m2) became neutropenic. Sensory neuropathy was dose-limiting. The maximum tolerated dose (MTD) was 250 mg/m2. Paclitaxel pharmacokinetic profiles in study patients were identical to those of previously reported patients with other solid tumors. CONCLUSION: The MTD of paclitaxel administered weekly for 6 weeks by 3-hour infusion is 250 mg/m2. Since patients with brain tumors often have preexisting neurologic deficits, we suggest 225 mg/m2 as the optimum dose for phase II trials in this group of patients.

Adult↗

PubMed1996

A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors.

BACKGROUND: Seizures occur after the diagnosis of brain tumors in up to 40% of patients. Prophylactic anticonvulsants are widely advocated despite a lack of convincing evidence of their efficacy in preventing first seizures. We conducted a randomized, double-blind, placebo-controlled study comparing the incidence of first seizures in divalproex sodium- and placebo-treated patients with newly diagnosed brain tumors. PATIENTS AND METHODS: Patients who had not previously had a seizure were randomized within 14 days of diagnosis of their brain tumor to receive either divalproex sodium or placebo. All patients had at least one supratentorial brain lesion, a Karnofsky Performance Score (KPS) > or = 50%, and no previous anticonvulsant use or other brain disease. Compliance and adequacy of dosing were assessed by pill counts and monthly blood levels. RESULTS: Seventy-four of 75 consecutive eligible patients were entered in this study. Median follow-up was 7 months. The drug and placebo groups did not differ significantly in age, sex, KPS, primary tumor type, number or location of brain lesions, frequency of brain surgery, or pretreatment EEG. Thirteen of 37 patients (35%) receiving divalproex sodium and 9 of 37 patients (24%) on placebo had seizures. The odds ratio for a seizure in the divalproex sodium arm relative to the placebo arm was 1.7 (95% CI 0.6 to 4.6; p = 0.3). The hypothesis that anticonvulsant prophylaxis provides a reduction in the frequency of first seizure as small as 30% was rejected (p = 0.05). CONCLUSIONS: Anticonvulsant prophylaxis with divalproex sodium is not indicated for patients with brain tumors who have not had seizures.

Anticonvulsants↗