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Biomedical subjects

R Wittes

Publications and source records attributed to R Wittes.

At least 19 recordsLinked to original sources
PubMed1999

Role of clinical trials informatics in the NCI's cancer informatics infrastructure.

A Web-enabled Cancer Informatics Infrastructure (CII) will enable faster, better clinical trials, ultimately improving cancer care. To create the CII, the National Cancer Institute is forming public-private partnerships and building on existing activities. Key innovations include development of standards for cancer patient information and clinical research, management of patients using disease specific "clinical states" and use of drag and drop electronic protocol authoring.

Breast Neoplasms↗
PubMed1998

Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS: Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS: The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION: The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.

Adult↗
PubMed1996

Intraocular levels of methotrexate after intravenous administration.

PURPOSE: To determine if adequate intraocular levels of methotrexate are achieved after intravenous administration. METHODS: After intravenous administration, methotrexate levels were determined in the serum, the anterior chamber, and the cerebrospinal fluids of a patient with recurrent ocular lymphoma. A fluorescence polarization immunoassay was used to make the determinations. RESULTS: At seven hours into a 24-hour intravenous infusion, methotrexate was at cytotoxic level in all samples. At 74 hours, cytotoxic levels were present only in the aqueous humor. CONCLUSION: Sustained cytotoxic ocular methotrexate levels are achievable after systemic administration.

Anterior Chamber↗
PubMed1996

Treatment of advanced solid tumors with immunotoxin LMB-1: an antibody linked to Pseudomonas exotoxin.

Immunotoxin LMB-1 is composed of monoclonal antibody B3 chemically linked to PE38, a genetically engineered form of Pseudomonas exotoxin. B3 recognizes a carbohydrate antigen (Le(Y)) present on many human solid tumors. LMB-1 has excellent antitumor activity in nude mice bearing Le(Y)-positive tumors. We conducted a phase I study of 38 patients with solid tumors who failed conventional therapy and whose tumors expressed the Le(Y) antigen. Objective antitumor activity was observed in 5 patients, 18 had stable disease, 15 progressed. A complete remission was observed in a patient with metastatic breast cancer to supraclavicular nodes. A greater than 75% tumor reduction and resolution of all clinical symptoms lasting for more than six months was observed in a colon cancer patient with extensive retroperitoneal and cervical metastasis. Three patients (two colon, one breast cancer) had minor responses. The maximum tolerated dose of LMB-1 is 75 microgram/kg given intravenously three times every other day. The major toxicity is vascular leak syndrome manifested by hypoalbuminemia, fluid retention, hypotension and, in one case, pulmonary edema. Although immunotoxins have been evaluated in clinical studies for more than two decades, this is the first report of antitumor activity in epithelial tumors.

Adult↗
PubMed1992

Recent National Cancer Institute lymphoma trials of etoposide-containing combination chemotherapy.

Short-course prednisone/doxorubicin/cyclophospha- mide/etoposide-cytarabine/bleomycin/vincristine/methotrexate (ProMACE-CytaBOM) contains the same drugs as standard ProMACE-CytaBOM but is delivered weekly for 16 weeks rather than 2 weeks out of 3 for 18 weeks. This results in a significant increase in dose intensity, ranging from 27% to 65% for all drugs. A total of 46 patients have been treated with short-course ProMACE-CytaBOM. The overall complete response rate of 91% and relapse rate of 17% compares favorably with results obtained using standard ProMACE-CytaBOM (86% and 27%, respectively). Toxicity was slightly greater with short-course therapy, but in general the regimen was well tolerated. Further dose intensification is possible in eligible patients by dose escalating myelotoxic drugs. A second strategy for augmenting the dose intensity is to deliver the drugs by continuous intravenous infusion. Infusional chemotherapy with doxorubicin/etoposide/vincristine/oral prednisone/bolus cyclophosphamide (EPOCH) results in significant antitumor activity in heavily pretreated patients with chemotherapy-resistant Hodgkin's disease and non-Hodgkin's lymphomas. Complete responses or partial responses were seen in 91% of 21 evaluable patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Therapeutic response in phase I trials of antineoplastic agents.

We analyzed the therapeutic effect reported in 187 phase I trials of 54 anticancer drugs introduced into National Cancer Institute-sponsored clinical trial from 1974 to 1982. An additional 12 drugs entering clinical trial prior to 1974 were also examined. Objective responses (partial and complete) were reported in 271 of the 6447 patients (4.2%). Thirty-nine percent of the patients were treated at an initial dose level greater than or equal to the dose ultimately recommended for phase II trials. Patients in phase I trials generally had adequate performance status (Karnofsky scale greater than 80% or Eastern Cooperative Oncology Group 0, 1, or 2). More than 90% of the patients had received prior chemotherapy. We next examined the therapeutic effect observed in phase II trials for each of the drugs. Thirty-eight of the 54 drugs had completed at least one phase II trial. Twenty-one drugs were rated active, and nine were rated inactive. For the drugs entering clinical trial since 1974, the median phase I response rate for those active in phase II was 4.3%, compared to 2.7% for the drugs not found active in phase II. This difference was not statistically significant. The tabulated response rate in phase I trials reported here should be interpreted cautiously. There are many factors which may contribute to significant variability in the reported response rates, including the heterogeneity of patient population with respect to prior therapy and tumor type, lack of requirement for measurable/evaluable disease on entry into many studies, and variations in the rigor with which tumor sites are followed for response. These factors may lead to either an overestimate or underestimate of the true response rate in phase I. Although little therapeutic effect is produced in phase I, we discuss several measures which might increase patient benefit during these trials.

Antineoplastic Agents↗
PubMed1984

Three cases of schistosomiasis mekongi from northern Laos.

Three cases of intestinal schistosomiasis acquired in northern Laos are reported. All three patients swam regularly for many years in the Mekong River near the cities of Vientiane and Luang Prabang. Morphology of the eggs found on rectal biopsy indicated infection with Schistosoma mekongi. One patient had severe portal hypertension with bleeding esophageal varices requiring a splenorenal shunt; studies of her liver biopsy showed S. mekongi eggs and periportal fibrosis. A second patient had abnormal liver function tests, and a third patient was asymptomatic. In two of the three cases, no schistosome eggs were found on stool examination, and the diagnosis was made by rectal biopsy. The implications of this new focus of infection are discussed.

Adult↗
PubMed1981

A phase II evaluation of m-AMSA, 4'-(9-acridinylamino) methanesulfon-m-anisidide, in patients with breast cancer.

A phase II study of m-AMSA, 4'-(9-acridinylamino) methanesulfon-m-anisidide was carried out in 40 patients with metastatic carcinoma of the breast. The drug, at a dose of 120 mg/m2, was given as a single intravenous injection every 3 weeks. One patient achieved a partial remission of 4 months duration; three patients experienced minor response. This study suggests that the true major response rate of advanced breast cancer to m-AMSA given in this manner is less than 13% at the 95% confidence level.

Adult↗