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Biomedical subjects

S Legha

Publications and source records attributed to S Legha.

14 recordsLinked to original sources
PubMed1999

Acute tumor lysis syndrome associated with concurrent biochemotherapy of metastatic melanoma: a case report and review of the literature.

BACKGROUND: Treatment of solid tumors rarely has been associated with tumor lysis syndrome. However, to the authors' knowledge the clinical scenario has not been reported previously in melanoma patients. METHODS: A patient with bulky metastatic melanoma was treated with concurrent biochemotherapy using interleukin-2, interferon-alpha, and a combination of cisplatin, vinblastine, and dacarbazine. RESULTS: Within 24 hours of the initiation of treatment, brisk tumor lysis occurred and led to a fatal outcome. CONCLUSIONS: Improvements in the treatment of solid tumors may increase the incidence of tumor lysis syndrome for tumors once believed to be marginally responsive. Oncologists should remain cognizant of this problem as more active regimens become available.

Acute Disease↗
PubMed1998

A prospective crossover randomized trial of novobiocin and rifampin prophylaxis for the prevention of intravascular catheter infections in cancer patients treated with interleukin-2.

BACKGROUND: The aim of this study was to determine the efficacy of novobiocin and rifampin as oral antibiotic prophylaxis for the prevention of catheter-related infection in melanoma patients treated with interleukin-2 (IL-2) plus interferon-alpha and chemotherapy (biochemotherapy). METHODS: Patients with advanced melanoma who were treated with biochemotherapy at the University of Texas M. D. Anderson Cancer Center were randomized in a crossover study to receive either oral antibiotic prophylaxis consisting of novobiocin and rifampin or observation alone over a 35-day course period. Patients were subsequently "crossed over" to the opposite arm of the study for an additional 35-day period, with each serving as his or her own control. RESULTS: Twenty-six patients were enrolled. Nine patients (35%) failed to tolerate oral antibiotics because of severe nausea and vomiting; 17 patients (65%) were crossed over and considered evaluable. During the control patient courses, 71% of evaluable patients had infectious complications, 41% had a catheter-associated bacteremia, and 53% had a local catheter infection. In contrast, of the patients treated with antibiotic prophylaxis, only 12% had an infectious complication (P = 0.001), 12% had a local catheter infection (P = 0.008), and 6% had catheter-associated bacteremias (P = 0.04). Thirty-six episodes of catheter infections occurred during the 17 control courses, whereas only 3 episodes occurred during antibiotic prophylaxis (P < 0.001). CONCLUSIONS: Although more than one-third of patients receiving IL-2 treatment with biochemotherapy failed to tolerate novobiocin and rifampin, this oral antibiotic regimen was efficacious in preventing the infectious complications, especially those associated with vascular catheters, in this high risk patient population.

Administration, Oral↗
PubMed1996

Phase Ia/Ib trial of anti-GD2 chimeric monoclonal antibody 14.18 (ch14.18) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in metastatic melanoma.

We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral nerve dysesthesias, myalgias, and weakness. Dose-limiting toxicity was observed at 60 mg/m2 and consisted of severe hypertension, hypotension, and atrial fibrillation in one patient each, respectively. Significant increases in white blood cell count, granulocyte count, eosinophil count, and monocyte count occurred after rhGM-CSF treatment. Significant enhancement of in vitro and in vivo monocyte and neutrophil tumoricidal activity and antibody-dependent cellular cytotoxicity along with significant elevations in C-reactive protein and neopterin were observed. Despite these immunological and biological changes, no antitumor activity was seen. In short, the combination of ch14.18 and rhGM-CSF resulted in toxicity similar to that observed with ch14.18 alone without improvement in tumor response.

Antibodies, Monoclonal↗
PubMed1989

Phase I clinical trial and pharmacokinetic evaluation of 4'-0-tetrahydropyranyladriamycin (THP-adriamycin).

Tetrahydropyranyladriamycin (THP-adriamycin) is an anthracycline analogue currently under development in Europe and Japan. Preclinical studies suggest that it may have greater activity and less cardiac toxicity than doxorubicin. We conducted a phase I clinical and pharmacologic study of THP-adriamycin given as a weekly 15-min infusion for 3 weeks, followed by 1 week of observation. Therapy was associated with minimal acute toxicity. The dose-limiting toxicity was neutropenia, usually maximal during the 4th week after treatment; alopecia was rare. The maximum tolerated dose was 25 mg/m2; for phase II studies using this schedule, a dose of 20 mg/m2 weekly for 3 weeks is recommended. Pharmacokinetic studies revealed a triphasic elimination of the parent compound with alpha, beta, and gamma half-lives of 5.6 min, 1.4 h, and 9.3 h, respectively. THP-adriamycin was rapidly taken up by blood cell components, with concentrations in red blood cells (RBCs), lymphocytes, and polymorphonuclear cells exceeding those in plasma. In all, less than 10% of the compound was eliminated in the urine within 24 h.

Chromatography, High Pressure Liquid↗
PubMed1989

Interleukin-2 alone and in combination with other cytokines in melanoma: the investigational approach at the University of Texas M.D. Anderson Cancer Center.

The clinical data that have been accumulated so far suggests a significant influence of IL-2 dose and schedule on the immunobiological effects and clinical toxicities observed with this cytokine. Consequently, the series of Phase I and Phase II clinical trials conducted at the University of Texas M. D. Anderson Cancer Center in patients with advanced malignant melanoma investigating the use of IL-2 in combination with other cytokines, monoclonal antibodies, or ex vivo activated effector cells have used a common dose and schedule of IL-2 administration for which abundant immunobiological information already exists. This approach allows cross-trial comparison of experience with toxicities, immunobiological observations and clinical activity by a group of investigators within a single institution, and more rapid and valid evolution towards combination biological therapy, which preclinical data suggest will have greater activity than single agent therapy.

Biological Factors↗
PubMed1987

Phase I trial of caracemide using bolus and infusion schedules.

We conducted a phase I trial of caracemide, a new chemotherapeutic agent, which is active in the MX1 (mammary) and CX1 (colon) human tumor xenografts. Using a 5-day bolus schedule, dose-limiting toxicity consisting of burning perioral pain associated with flushing, nasal stuffiness, and excess lacrimation was seen at 650 mg/m2/day. Using a 5-day continuous-infusion schedule, dose-limiting toxicity in the form of changes in affect, lethargy, disorientation, and cognitive dysfunction with electroencephalogram abnormalities was noted at 800 mg/m2/day. The recommended phase II dose levels are 525 mg/m2/day using the 5-day bolus schedule and 650 mg/m2/day using the continuous-infusion schedule. Because of venous pain at the site of infusion, the drug must be delivered via central venous access. The pathophysiology of both the peripheral and central side effects of caracemide may be related to increased cholinergic activity.

Adult↗
PubMed1982

Phase II trial of m-AMSA in hepatocellular carcinoma: a Southwest Oncology Group Study.

Twenty-three patients with heptocellular carcinoma were treated with m-AMSA at a dose of 120 mg/m2 iv repeated at 4-week intervals. Toxicity was primarily hematologic. Partial responses occurred in two of 14 previously treated patients and in one of nine previously untreated patients. The overall activity of m-AMSA in patients with hepatocellular carcinoma appears minimal.

Adolescent↗
PubMed1982

High-dose AMSA and bone marrow rescue in patients with solid tumors.

The feasibility of high-dose AMSA followed by autologous bone marrow rescue was studied in seven patients with solid tumors. They received a total of 12 courses of treatment. Total doses ranged from 600 to 1000 mg/m2/course. Major toxic effects were myelosuppression, fever of unknown origin, and stomatitis. One patient with malignant melanoma had stable disease lasting 2 months; the other six had progressive disease.

Aminoacridines↗
PubMed1979

Clinical studies with rubidazone.

One hundred and thirty-three patients, 94 with acute luekemia and 39 with solid tumors, received rubidazone, alone or in combination, at M. D. Anderson Hospital. The initial study, a phase I--II study carried out in 39 patients with acute leukemia, revealed substantial antileukemic activity with optimal results at a dose level of 450 mg/m2. Toxic manifestations included an acute reaction suggestive of histamine release with dose-limiting mucositis at a dose of 600 mg/m2. Forty-seven patients with acute leukemia were treated at phase II dose levels. Thirteen of 32 patients (42%) with acute myelogenous leukemia and seven of ten patients (70%) with acute lymphocytic leukemia achieved complete remission. Twenty-seven previously untreated patients with acute leukemia who were greater than 50 years old were treated with rubidazone in combination with cytosine arabinoside, vincristine, and prednisone. Fifteen patients (50%) achieved complete remission including 12 of 15 patients (73%) who were treated at a dose of 200 mg/m2 of rubidazone on Day 1 and a dose of 70 mg/m2/day X 7 days of cytosine arabinoside (continuous infusion). For patients with solid tumors, the dose-limiting toxic effect was myelosuppression at a dose of 200 mg/m2. Other toxicity at that dose level was minimal. The best responses were seen in patients with carcinoma of the period with two of four evaluable patients showing objective tumor regression. Of six previously untreated patients with thyroid carcinoma none responded, and in a phase II study of patients with breast cancer there were no partial remissions among 13 patients. Cardiac toxicity, manifested by congestive heart failure, occurred in seven patients at cumulative doses of 1050--2600 mg/m2 of rubidazone; all patients had had prior anthracycline therapy at low doses. Rubidazone has been shown to be an active antileukemic agent, but appears to be less active than Adriamycin in our studies of patients with solid tumors.

Acute Disease↗