Biomedical subjects

Jan C Buckner

Publications and source records attributed to Jan C Buckner.

42 records · Page 3Linked to original sources

PubMed2002

Safety of thrice-daily hyperfractionated radiation and BCNU for high-grade gliomas.

PURPOSE: To investigate the safety of thrice-daily hyperfractionated radiotherapy (RT) given in conjunction with BCNU (carmustine) in high-grade gliomas. METHODS AND MATERIALS: Patients >18 years old with newly diagnosed high-grade gliomas were eligible. The dose of radiation was 5040 cGy, with a 1440-cGy boost in 180 cGy fractions delivered thrice daily in two 6-day periods with a 2-week interval. BCNU (200 mg/m(2)) was administered on the first day of radiation, then every 7 weeks for 1 year and every 10 weeks for another year. RESULTS: Eighteen patients were enrolled. The mean age was 49.6 years. Sixteen patients had astrocytomas (Grade 3 or 4 in 5 and 11 patients, respectively) and 2 had oligoastrocytomas (Grade 3 and 4 in 1 patient each). One underwent total resection, 9 subtotal resection, and 8 biopsy only. Thirteen patients had stable disease, 4 regression, and 1 progression. The median time to progression was 37.8 weeks. The median overall survival was 44.4 weeks. Nine patients had neurologic toxicities, including 2 deaths at 69 and 139 weeks. CONCLUSION: This regimen is unacceptably toxic. Factors that could have contributed to the toxicity may include the total radiation dose, thrice-daily hyperfractionation, and the concurrent use of i.v. BCNU.

Adult↗

PubMed2002

Chemotherapy, irradiation, and surgery for function-preserving therapy of primary extremity soft tissue sarcomas: initial treatment with ifosfamide, mitomycin, doxorubicin, and cisplatin plus granulocyte macrophage-colony-stimulating factor.

BACKGROUND: Most institutional teams utilize multimodality therapy in their efforts to cure patients with primary high-grade extremity soft tissue sarcomas, although the value of adjuvant systemic chemotherapy is still disputed by some oncologists. This single-institution Phase II study describes an effort to control metastasis by the use of two cycles of chemotherapy as the initial preoperative treatment. METHODS: Between March 1994 and October 1997, 20 women and 19 men with primary extremity or limb girdle high-grade soft tissue sarcomas were registered to a study of preoperative ifosfamide, mitomycin, doxorubicin, cisplatin (IMAP) plus granulocyte macrophage-colony-stimulating factor (GM-CSF) followed by preoperative irradiation and subsequent limb-sparing surgery. The two sequential monthly cycles of IMAP involved intravenous ifosfamide, 2500 mg/m(2), and mesna, 2500 mg/m(2), on Day 0, followed by identical doses of these agents plus intravenous mitomycin, 4 mg/m(2), doxorubicin, 40 mg/m(2), and cisplatin, 60 mg/m(2), on Day 1. Sargramostim (GM-CSF) 250 microg/m(2) was given subcutaneously every 12 hours for 4 days beginning 6 days before the chemotherapy, and then for 14 more days beginning the day after chemotherapy was completed. At the beginning of the third month, external beam irradiation was administered daily, 5 days each week for 5 consecutive weeks to total preoperative doses of 4500 centigrays (cGy). This was accompanied by reduced doses of MAP chemotherapy (mitomycin, 6 mg/m(2), doxorubicin, 30 mg/m(2), and cisplatin, 45 mg/m(2)) intravenously on Days 0, 21, and 42 of the radiation therapy segment. Approximately 1 month after preoperative irradiation ended, each patient had complete surgical excision with curative intent, using limb-sparing techniques when possible. Radiation to total doses of 5500-6500 cGy was accomplished by delivery of an additional 1000-2000 cGy to the tumor bed via intraoperative electron beam, brachytherapy, or external beam irradiation at the completion of surgery. RESULTS: All except 5 patients had tumors at least 5 cm in diameter. Chemotherapy toxicity grade three or higher consisted primarily of vomiting (23%), leukopenia (54%), and thrombocytopenia (77%). Six patients have died of metastatic sarcoma, and one other died in a motorcycle accident. Kaplan-Meier curves indicate estimated 5-year survival of approximately 80% and freedom from metastasis at 2 years of approximately 85%. CONCLUSIONS: IMAP plus GM-CSF is satisfactory as initial treatment for primary extremity soft tissue sarcomas in two monthly cycles preceding irradiation. The prescribed irradiation was generally tolerable and effective in permitting limb-sparing surgery. Although the outcome of patients treated on this regimen has been favorable, the metastasis problem has not been eliminated.

Adult↗

PubMed2002

Triple-dose contrast/magnetization transfer suppressed imaging of 'non-enhancing' brain gliomas.

PURPOSE: Triple-dose (TD) gadolinium contrast administration and magnetization transfer suppression (MTS) in brain magnetic resonance imaging (MRI) have proven to be useful for demonstrating additional enhancing lesions in some diseases. The purpose of this study was to determine if there is a subset of brain tumors that demonstrate contrast enhancement with TD and MTS that do not enhance with standard imaging and standard contrast dose. MATERIALS AND METHODS: Fifteen patients with either newly diagnosed primary brain tumor or brain tumor that had been followed for more than 2 years were enrolled. T1-weighted MTS images without IV contrast, with 0.1 mmol/kg without MTS (single-dose (SD) images), and with additional 0.2 mmol/kg gadolinium and MTS ('TD/MTS') were obtained. RESULTS: None of the patients had enhancement on SD images. Six patients had areas of enhancement on TD/MTS images ('exact' chi-squared p = 0.017). CONCLUSION: A statistically significant increased rate of contrast enhancement was found on TD/MTS images in patients whose tumors did not enhance at single dose without MTS. It is possible that small areas of enhancement seen only with TD/MTS might represent areas of higher-grade tumor.

Brain Neoplasms↗

PubMed2002

Contrast of response to dacarbazine, mitomycin, doxorubicin, and cisplatin (DMAP) plus GM-CSF between patients with advanced malignant gastrointestinal stromal tumors and patients with other advanced leiomyosarcomas.

BACKGROUND: Previous observations have suggested that leiomyosarcomas, and especially gastrointestinal leiomyosarcomas, may be less responsive to cancer chemotherapy than other histologic types of non-osseous sarcomas; however, this difference has not been characterized well until quite recently, with the recognition of the special identity of gastrointestinal stromal tumors (GIST). Prior to the general acceptance of this new histologic classification, we decided to study patients with gastrointestinal leiomyosarcomas in concert with other leiomyosarcomas for relative responsivity to a combination cytotoxic regimen developed specifically for leiomyosarcomas. PATIENTS AND METHODS: Adult patients with advanced leiomyosarcomas received intravenous chemotherapy as outpatients with dacarbazine 750 micrograms/m2, mitomycin 6 mg/m2, doxorubicin 40 mg/m2, and cisplatin 60 mg/m2 on day 0, with granulocyte macrophage colony stimulating factor (GM-CSF, sagramostim) 250 mcg/m2 given s.c. every 12 hr on days -6 to -3 and on days 1-14 of each 4-week treatment cycle. Our original plan to escalate dacarbazine doses to 1000 mg/m2 following cycle one was abandoned after the first six patients because of toxicity. RESULTS: We studied 21 patients with GIST and 18 patients with other types of leiomyosarcomas, for a total of 131 treatment cycles, with a median of four cycles per patient in each of the two groups of patients. Toxicity was significant, with 33% having grade 3 vomiting at some time during treatment. Grade 3 leukopenia occurred in 42%, and grade 3 thrombocytopenia was observed in 68% of our patients. In one patient, grade 4 pulmonary toxicity developed during the fourth cycle, and this was considered a major factor in her death. Objective tumor regression was observed in one of 21 (1.8%) (95%CI = 0-14.5%) GIST and in 11 of 18 (61%) (95%CI = 38-84%) other leiomyosarcomas, including eight of 10 uterine cases. In five cases, we interrupted chemotherapy to attempt complete surgical excision of residual tumor, and four of the patients were rendered apparently free of disease. Median survivals for the two groups have been similar with 16.7 months (95%CI = 8.8-27.5 months) for the GIST and 17.5 mos (95%CI = 10.9-35.3%) for the other leiomyosarcomas. Three patients with uterine leiomyosarcomas are still alive more than 2 years after completing this chemotherapy and subsequent secondary surgical excision (+/- irradiation) and two of them are free of disease. CONCLUSIONS: While this regimen is ineffective against GIST, its value against uterine leiomyosarcomas deserves further study in a larger population.

Adult↗

PubMed2002

Prognostic significance of an apoptotic index and apoptosis/proliferation ratio for patients with high-grade astrocytomas.

We evaluated the association of spontaneous apoptosis and an apoptosis/proliferation index with survival to determine the potential of such measures to serve as predictive markers for patients with glioblastoma multiforme (GBM). We examined the extent of spontaneous apoptosis in tumors from newly diagnosed patients, 75 with GBM and 21 with anaplastic astrocytoma, who were entered on treatment protocols of the North Central Cancer Treatment Group. In the group of GBM patients, those with a higher apoptotic index tended to live longer ( P = 0.04; Cox proportional hazards model including performance score, age, and extent of resection in a multivariate model). We found that the apoptotic index values for anaplastic astrocytoma patients tended to be lower than those in the GBM patients, although with small sample sizes, the result was not statistically significant ( P = 0.1). We also examined expression of the Ki-67 cell proliferation antigen immunohistochemically using the MIB-1 monoclonal antibody. Ki-67 expression did not provide additional information regarding the survival of patients with GBM. In this group of GBM patients, those patients with higher apoptotic index/proliferation ratios had a better prognosis than did those with a low ratio ( P < 0.021, same model as above). These findings suggest that both apoptosis and a cell death/cell proliferation ratio are associated with patient survival, and they may be useful for either the clinical evaluation of patients with GBM or the stratification of patients for treatment evaluation.

Adult↗

PubMed2002

Randomized, placebo-controlled, phase III surgical adjuvant clinical trial of megestrol acetate (Megace) in selected patients with malignant melanoma.

A randomized, double-blind, placebo-controlled phase III clinical trial was performed to assess megestrol acetate (Megace) as a postsurgical adjuvant therapy for patients with locally advanced malignant melanoma. Patients whose tumors were greater than 1.7 mm thick and had no regional lymph node involvement and patients with regional lymph node involvement were randomized to receive either 160 mg twice per day oral suspension of megestrol acetate or placebo. Treatment was administered for a maximum of 2 years or until disease progression. The study accrued 262 eligible patients. All but two patients were followed until death or a minimum of 4.5 years. Disease progression was documented in 156 patients. Neither progression-free survival (PFS) nor overall survival (OS) was found to differ between the treatments. The median PFS was 2.4 years in the megestrol acetate arm and 2.3 years in the placebo arm. Multivariate analysis revealed a significantly decreased PFS for patients with four or more positive regional lymph nodes and metachronous nodal disease. Median OS was 5.3 years in the megestrol acetate arm and 3.9 years in the placebo arm. Multivariate analysis revealed that OS was significantly decreased for patients 70 years of age or older with four or more positive lymph nodes. Adjuvant therapy with megestrol acetate oral suspension administered at a dose of 160 mg twice a day for 2 years was not found to be effective in prolonging PFS or OS in patients with surgically resected, locally advanced melanoma.

Adult↗