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Biomedical subjects

G B Magill

Publications and source records attributed to G B Magill.

At least 19 recordsLinked to original sources
PubMed1994

Biological study of R24 mouse monoclonal antibody in patients undergoing thoracotomy for pulmonary metastases from soft tissue sarcoma.

The disialoganglioside GD3 is expressed on the surface of soft tissue sarcoma, malignant melanoma, and other malignant cells and is, therefore, a potential target for therapeutic monoclonal antibodies. Intravenously administered R24, a murine IgG3 monoclonal antibody to GD3, induces inflammation and tumor regression at sites of metastatic malignant melanoma. R24 5 mg/m2 was given intravenously every other day for six doses to 10 patients with pulmonary metastases from a primary soft tissue sarcoma of the extremity for whom thoracotomy was planned. Resected tissue was available from 7 patients. All metastases expressed GD3; however, expression was heterogeneous within tumors, and in no tumor were more than 80% of the cells GD3 positive. A mild to moderate infiltrate consisting of mononuclear cells with T-cell markers was identified around or within pulmonary metastases in 6 patients. Tolerable acute allergic reactions occurred in all patients, but 3 patients had severe chest tightness and bronchospasm that limited the planned therapy. The setting of thoracotomy for metastatic disease provides an ideal system for studies on the pharmacology and biological effects of monoclonal antibodies that target soft tissue sarcoma antigens.

Adult↗
PubMed1991

A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors.

A prospective randomized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin (60 mg/m2 every 3 to 4 weeks) administered by bolus or 72-hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high-grade soft tissue sarcoma of the extremity or superficial trunk. Cardiac toxicity, defined as a 10% or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography, was evaluated in 69 patients. Cardiotoxicity was seen in 61% of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2. Among patients who received continuous infusion, 42% had cardiotoxicity with a median dose of 540 mg/m2. The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm (P = 0.0017). Two patients in each group had clinical congestive heart failure, with one cardiac death occurring in each. There was a trend toward a lower rate of metastasis (P = 0.19) and a significantly lower rate of death of disease (P = 0.036) for patients treated with the bolus dose. Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis: blood transfusion within 24 hours of operation (P less than 0.00001), tumor deep to the fascia and 5 cm or more in size (P = 0.0043), and a histologic subtype other than liposarcoma (P = 0.0002). The unfavorable effect of continuous infusion was not selected in the model (P = 0.16). Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational. Furthermore, the impact of perioperative blood transfusion merits further study.

Adult↗
PubMed1991

A phase II trial of PALA + dipyridamole in patients with advanced soft-tissue sarcoma.

A total of 21 patients with advanced soft tissue sarcoma enrolled in a phase II trial of 3.5 g/m2 N-phosphonacetyl-L-aspartate (PALA) given intravenously every 3 weeks plus 50 mg/m2 dipyridamole (Persantine) given orally every 6 h. Dipyridamole administration was initiated 1 week before the first dose of PALA. Peak and trough plasma concentrations of dipyridamole were measured before and after the first dose of PALA in 14 patients. In all, 19 patients were evaluable for therapeutic response. One subject experienced partial regression of a pulmonary metastasis; no other major response was observed. Diarrhea was the most prominent toxicity; in one patient it was life-threatening and was associated with a severe rash. On the day preceding PALA administration, the median peak plasma concentration of dipyridamole was 2,208 ng/ml and the median trough value was 904 ng/ml. Similar values were obtained on the day of PALA administration. Although the levels achieved were similar to those required to modulate the activity of PALA in preclinical systems, the therapeutic results obtained in the present study were not superior to those reported for PALA alone in previously treated patients with soft-tissue sarcoma.

Adult↗
PubMed1990

Central venous catheter complications in sarcoma patients receiving adjuvant chemotherapy.

As part of a prospective randomized study in patients with high grade soft tissue sarcoma (STS), 47 patients received post-operative adjuvant Adriamycin. The method of administration was randomized to intravenous bolus (B) or to continuous 72 hour infusion (CI) via a Silastic right atrial catheter. Both groups received 60 mg/m2 every 3 weeks. There were nine hospital admissions for treatment related complications in four of the 26 CI patients compared to none in the 21 B patients (P = 0.03). All of the admissions related to complications involving the central venous catheter (CVC). This apparent increased risk for hospital admission secondary to treatment related complications in patients treated with CI must be considered in the planning of future therapeutic trials.

Catheterization, Central Venous↗
PubMed1989

The influence of antineoplastic chemotherapy on antipyrine metabolism in man.

When either Doxorubicin or Mitomycin-C was administered to patients, antipyrine clearance was respectively unaltered or increased. Antipyrine was administered to patients two days prior to and one day after their first course of the chemotherapeutic drug. Antipyrine clearance increased an average of 11.2% in the 5 patients that received Doxorubicin (not significant) and 15.2% in the six patients that received Mitomycin-C (P = 0.033, students t-test). The altered clearance is likely due to a rapid induction of the mixed function oxidase system by the chemotherapy as other parameters that could influence clearance were stable throughout the study (volume of distribution, weight, creatinine clearance and liver function tests). It is unlikely that the prechemotherapy antipyrine dose accounted for this change. The administration of these two antitumor antibiotics in humans may modestly increase the mixed function oxidase activity that is responsible for the metabolism of antipyrine. These findings are in direct contrast to markedly decreased mixed-function oxidase activity observed in the rodent pretreated with the same chemotherapy.

Adult↗
PubMed1988

Etoposide (VP-16) in the treatment of advanced adenocarcinoma of the pancreas.

Twenty-six patients with advanced adenocarcinoma of the pancreas were treated with etoposide (VP-16), 100-180 mg/m2 i.v., days 1, 2, and 3, monthly. Twenty-five had bidimensionally measurable disease and one had evaluable disease only. This regimen and dosage schedule were well tolerated, with minimal toxicity including myelosuppression; a median WBC count nadir of 3,600 cells/mm3 (range 200-2,400); and a median platelet nadir of 215,000 cells/mm3 (range 15,000-405,000). However, no patients responded and only two had stable disease for 3.5 and 4 months, respectively. At this dosage and schedule, there is no role for VP-16 in the treatment of advanced pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1988

Phase II trial of menogarol in the treatment of advanced adenocarcinoma of the pancreas.

Fifteen patients with advanced adenocarcinoma of the pancreas were treated with menogarol 150-225 mg/m2 i.v. every 3 weeks. All patients had bidimensionally measurable disease. This regimen and dosage schedule are well tolerated, with minimal toxicity that included myelosupression; median white blood cell (WBC) count nadir of 2,700 cells/mm3 (range 1,400-7,100 cells/mm3) and median platelet nadir of 162,000 cells/mm3 (range 53,000-390,000 cells/mm3). Anorexia occurred in one patient, nausea or vomiting in six, phlebitis in one, and alopecia in six patients. No patients responded. At this dosage and schedule, there is no role for menogarol in the treatment of advanced pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1987

Cisplatin. A phase II evaluation in previously untreated patients with soft tissue sarcomas.

A Phase II trial of moderately high-dose cisplatin (120 mg/m2 with mannitol diuresis) was conducted in 26 previously untreated patients with soft tissue sarcomas. One partial response (major response rate, 4%) and two minor responses were seen. Severe nausea and vomiting and transient increases in the serum creatinine level were the most common side effects of treatment. Cisplatin has minimal activity as a single agent in patients with soft tissue sarcoma.

Adult↗
PubMed1986

Recurrent epidermoid cancer of the anus.

Of 83 patients with recurrent epidermoid cancer of the anus, 67 had tumors in the anal canal and 16 had tumors at the anal margin. Local pelvic or perineal recurrence after abdominoperineal resection of tumors in the canal had a poor prognosis. Median survival after combination chemotherapy and megavoltage irradiation was 14 months. With irradiation alone, median survival was 7 months, although nearly half of these patients had been treated with orthovoltage techniques. Untreated patients with visceral metastases had a median survival of 8 months, but no improvement in survival was seen after treatment with chemotherapy. In contrast, patients who had metastases in inguinal lymph nodes had a 55% 5-year survival rate after inguinal dissection. Patients with tumors at the anal margin did not have visceral metastases. This is an important difference between tumors arising in the canal and those arising at the anal margin. Local excision was satisfactory treatment for 90% of the patients who had local recurrence in the perianal skin; abdominoperineal resection was rarely required. Inguinal lymph node metastases from margin cancer are uncommon, but three of five such patients survived 5 years after groin dissection. A combination of 5-fluorouracil, mitomycin C, and radiation therapy was used for patients with pelvic recurrence after abdominoperineal resection of epidermoid cancer of the anal canal. In this study, there was no evaluation of the role of megavoltage irradiation alone at the recommended doses of 5500 to 6000 rad for these patients. Some patients with visceral metastases respond to combination chemotherapy, but median survival is not improved; evaluation of new chemotherapeutic regimens is required. Patients with canal tumors metastatic to inguinal nodes should be treated by groin dissection as their prognosis is relatively good. Local recurrence of tumors at the anal margin can be satisfactorily treated by further local excision; those patients with margin tumors metastatic to inguinal nodes require groin dissection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Imaging of human tumors and organs with N-13-labeled L-methionine.

The work described herein is the first reported use of nitrogen-13-labeled L-methionine in human subjects. Three volunteers and 14 patients with a variety of solid tumors were scanned after intravenous administration of L-(N-13) methionine. In both volunteers and cancer patients, uptake of label was seen in the liver and pancreas, with smaller amounts of label detected in the heart, urinary bladder, and salivary glands. Concentration of N-13 in tumor was seen in 12 of the 14 cancer patients. Five had repeat studies after chemotherapy; in each case, the change in tumor uptake of N-13 after N-13 methionine injection paralleled the clinical response to chemotherapy. Three patients had L-(N-13) glutamate scans the same day that they were studied with N-13 methionine. Concentration of the radiolabel in the tumor was very similar for the two compounds in each case. The systemic distribution of N-13 from methionine is similar to that from glutamate, except for a much smaller myocardial uptake and a prominent accumulation in the intestinal region. It is concluded that L-(N-13) methionine is potentially useful as a biologically significant agent for tumor visualization and assessment of therapeutic response.

Adolescent↗
PubMed1986

Chemotherapy for soft tissue sarcoma.

Adriamycin is the only active single agent for patients with metastatic sarcoma; combination chemotherapy regimens that omit Adriamycin are ineffective in adults. Despite early success with CYVADIC, there have been recent doubts regarding its efficacy. No other chemotherapeutic combination has provided consistently better results than CYVADIC. As complete responses occur in less than 15 per cent of patients there is a need for further evaluation of new regimens. It is necessary to evaluate new regimens in prospective, randomized studies. Response criteria should be consistent and reproducible. Attenuation schedules and data relating to the total administered dosage should be provided. It would also be beneficial to analyze prognostic variables so that patients liable to an unfavorable outcome could be identified before commencement of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Phase II trial of methylglyoxal-bis-guanylhydrazone (methyl-GAG) in patients with soft-tissue sarcomas.

A phase II study of Methylglyoxal-bis-guanylhydrazone (Methyl-GAG) was conducted on 20 previously treated patients with soft-tissue sarcomas. No major responses were seen among 18 adequately treated patients. Toxicity including severe fatigue, muscle pains, and pharyngitis was noted in most patients. Methyl-GAG does not have significant antitumor activity in previously treated patients with soft-tissue sarcomas.

Adolescent↗
PubMed1984

MIFA III (mitomycin-C, 5-fluorouracil, and adriamycin) chemotherapy for advanced adenocarcinoma of the pancreas.

Twenty-nine patients with advanced adenocarcinoma of the pancreas were treated with a combination of mitomycin-C, 5-fluorouracil, and adriamycin (MIFA III). Four of these patients achieved a partial response, and two achieved a minor response. An additional seven patients had evidence of disease stabilization. The median survival period from initiation of therapy for responders was 13.5 months as compared to 7.6 months for those with stable disease and 3.2 months for nonresponders (p = 0.001). Myelosuppression was the primary toxicity. Prolongation of survival was demonstrated in responding patients who had failed prior chemotherapy. The MIFA III regimen is active, well tolerated, and warrants further investigation in previously untreated patients.

Adenocarcinoma↗
PubMed1983

Chemotherapy of patients with advanced soft tissue sarcoma with use of DVA (vindesine sulfate), adriamycin and cyclophosphamide (DAC).

Thirty-four patients with advanced soft tissue sarcoma were treated with a three-drug combination including vindesine sulfate (DVA), Adriamycin, and cyclophosphamide (DAC) (S9). Thirty-one patients are evaluable of whom 23 were previously untreated. Among the latter group there were six complete responses (26%) and five partial responses (22%), for a major response rate of 48%. No major responses were seen in the eight previously treated patients. The median duration of responses was 8 months. Leukopenia and peripheral neuropathy were the major complications of treatment. Gastrointestinal toxicity was mild. Adriamycin cardiotoxicity was seen in two patients. Although the overall response rate to DAC is comparable to that of other combinations, it may offer the advantages of an increased complete response rate and less gastrointestinal toxicity.

Antineoplastic Agents↗
PubMed1983

Extraosseous osteogenic sarcoma. A review of 48 patients.

The clinical records and histologic material of 48 patients with extraosseous osteogenic sarcoma were reviewed. Most patients developed their tumors in the fifth or sixth decades of life. Five patients (10%) developed neoplasms in an area of prior radiation therapy, a median of 15 years after their exposure. Six patients (13%) related a history of trauma to the area where their extraosseous osteogenic sarcoma developed. The course of most patients was that of multiple local recurrences (69%) followed by pulmonary metastases (80%) and death (76%). Amputation or wide resection followed by irradiation appeared to be the most effective types of therapy, with median survivals greater than 60 months for patients receiving these treatments, compared to 28 months for patients initially treated with resection alone. Chemotherapy was not effective for patients with advanced disease; however, adjuvant chemotherapy after surgery may have been of value. Four of five patients who received adjuvant chemotherapy after surgery are alive and disease-free; the only two survivors after development of pulmonary metastases received adjuvant chemotherapy after surgical resection of visible pulmonary metastases.

Adolescent↗
PubMed1983

Preoperative chemotherapy and radiation therapy in the management of anal epidermoid carcinoma.

Management of epidermoid carcinoma of the anus has been primarily surgical in the past. Since it is a relatively rare entity, meaningful survival statistics are difficult to obtain. Five-year survival rates fall between 35 and 68% in patients treated with surgery and/or radiotherapy. Based on preliminary studies indicating promising results with the use of mitomycin C and 5-fluorouracil (5-FU) chemotherapy combined preoperatively with radiation therapy, these authors initiated a protocol in 1973 utilizing this multimodality approach. The preoperative treatment consisted of mitomycin C 15 mg/m2 IV bolus on day 1 and 5-FU 750 mg/m2/24 hours continuous infusion for five days. Radiation followed chemotherapy and consisted of 3000 rad given at 200 rad per day for 15 fractions. Of 37 patients entered on the protocol, 30 had primary disease and seven had been previously treated and had local recurrences. Median follow-up has been 28 months (range, 5-74 months). Of 31 patients with measurable lesions, 29 (94%) had major clinical responses (CR + PR) to the combined chemotherapy and radiation. Pathologic responses were also impressive with 53% (17/32) showing no evidence of residual tumor in the subsequently resected surgical specimen. Of the 37 patients treated, seven (19%) have had recurrences. The recurrence rate was 4/17 (24%) for those who had local excision following complete response to therapy as opposed to 3/18 (17%) for those treated by abdominoperineal resection. Thus it appears that the combination of preoperative mitomycin C and 5-FU with radiotherapy is effective at least in significantly downstaging this uncommon malignancy. Its ultimate effect on recurrence rate and overall patient survival awaits longer follow-up.

Adult↗
PubMed1983

Phase II evaluation of m-AMSA (4'-(9-acridinylamino)-methanesulfon-m-anisidide) in patients with adenocarcinoma of the pancreas.

m-AMSA (4'-(9-acridinylamino)-methanesulfon-m-anisidide, a substituted acridine derivative, was administered to 27 patients with adenocarcinoma of the pancreas. The dose ranged from 90-210 mg/m2/course. The toxic effects were primarily hematologic. Twenty-four of the patients were evaluable for response. These patients received a median of 2 doses (range 1-7). The median time from diagnosis to therapy was 2 months (range 0-16). Two patients achieved an MR lasting 4 and 2 months, respectively. Two patients had stabilization for 6 and 3 months. The median survival for all patients was 3 months. Survival distribution for patients with prior chemotherapy versus no previous therapy was not significantly different (p = 0.5). This study suggests that m-AMSA has little value as a single agent in the treatment of adenocarcinoma of the pancreas.

Adenocarcinoma↗