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Biomedical subjects

M A Burgess

Publications and source records attributed to M A Burgess.

At least 19 recordsLinked to original sources
PubMed1979

Combined chemoimmunotherapy for advanced breast cancer: a comparison of BCG and levamisole.

One hundred and fourteen evaluable patients with metastatic breast cancer were treated with a program consisting of 5-FU, Adriamycin, cyclophosphamide (FAC) and nonspecific immunotherapy with Levamisole. The results of this treatment program were compared to those observed with FAC and Bacillus Calmette Guerin (BCG) and FAC chemotherapy alone, both groups treated prior to the study reported in this paper. The overall response rates and complete response rates for all three treatment regimens were identical. The duration of remission, survival of all patients and survival of responders was similar for both chemoimmunotherapy regimens, being superior to the FAC chemotherapy alone group. Immunotherapy with Levamisole was well tolerated and side-effects were experienced by less than one-fourth of the patients. Overall, Levamisole was better tolerated than BCG and was easier to administer than the latter drug. These results suggest than nonspecific immunotherapy with Levamisole might prolong remission and survival of patients with metastatic breast cancer. Since the results achieved with BCG and Levamisole appear similar, the therapeutic ratio favors the use of Levamisole.

Antineoplastic Agents↗
PubMed1979

Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG.

One hundred and five patients with metastatic breast cancer were treated with 5-fluorouracil, Adriamycin, cyclophosphamide and BCG (FAC-BCG). The results were compared to those observed in a group of 44 patients treated with FAC chemotherapy alone. Although the overall response rates were similar (76% for FAC-BCG and 73% for FAC), the duration of remission was of 9 months for FAC and 14 months for FAC-BCG (p = 0.04). Similarly, survival or responding patients treated with FAC-BCG was significantly longer (24 months) than that observed in the chemotherapy alone treated group (15 months). There was no difference in survival or duration on study for non-responders. Response rates were not influenced by dominant site of disease, menopausal status or disease-free interval. The duration of remission and survival, however, were significantly longer for patients with bone and soft tissue involvement than for patients with visceral metastasis. Similarly patients with 1 or 2 metastatic sites survived significantly longer than those with more than 3 organ sites involved (p = 0.02). This chemotherapeutic combination is highly effective in inducing remissions. In addition, nonspecific immunotherapy with BCG appears to prolong duration of remission and survival for responding patients.

Adult↗
PubMed1979

Ftorafur, adriamycin, cyclophosphamide and BCG in the treatment of metastatic breast cancer.

Ftorafur is a 5-fluorouracil analogue which is slowly metabolized to 5-FU, resulting in prolonged therapeutic levels of this latter drug. Ninety-one evaluable patients with metastatic breast cancer were treated with Ftorafur, Adriamycin, cyclophosphamide, and BCG (ACFTOR-BCG), in an attempt to increase the effectiveness of the program or decrease its myelosuppressive toxicity. The results of this trial were compared to those previously reported with the combination of 5-FU, Adriamycin, cyclophosphamide, and BCG (FAC-BCG). Overall objective response rates were 65% and 76% for ACFTOR-BCG and FAC-BCG, respectively. Durations of response were 12 months and 14 months for ACFTOR-BCG and FAC-BCG (p = 0.53). The median survival of responders was 22 and 23.9 months, respectively. Substantial toxicity was observed with Ftorafur: nausea and vomiting severe enough to cause weight loss was observed in a substantially higher fraction of the patients treated with this drug than with 5-FU. Other side-effects, which were not observed with the 5-FU combination, were somnolence, dizziness, personality changes, tremor, ataxia, and confusion. No differences in myelosuppressive toxicity were observed between the two combinations, and the incidence of infectious complications was identical. The combination of Ftorafur, Adriamycin, cyclophosphamide and BCG did not offer any advantages with respect to increased effectiveness or reduced toxicity over the FAC-BCG regimen in breast carcinoma.

Adult↗
PubMed1979

Neocarzinostatin: a phase I clinical trial with five-day intermittent and continuous infusions.

Neocarzinostatin, a polypeptide antibiotic, was administered by both continuous and intermittent intravenous infusion to 76 patients with a variety of malignant diseases. Doses ranged from 500 to 6500 units/m2 X 5 days. With levels greater than or equal to 1800 units/m2, bone marrow suppression (particularly thrombocytopenia) was the dose-limiting toxicity. Delayed bone marrow recovery was less dose-dependent and occurred in 58% of initial treatment courses in solid tumor patients. Allergic reactions were more frequent with intermittent than with continuous infusions (20% vs. 2% of courses). No complete or partial remissions were observed among solid tumor patients although clinical improvement was noted in one patient with mycosis fungoides and one patient with multiple myeloma. One complete and two partial remissions were noted among 21 patients with acute leukemia. There was one complete remission in a patient with chronic leukemia. Leukemic patients on intermittent therapy evidenced greater change in bone marrow cellularity than those treated by continuous infusion. Although neocarzinostatin has some activity in the treatment of acute leukemia, continuous infusion offers no advantage over intermittent therapy.

Antibiotics, Antineoplastic↗
PubMed1979

Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG.

One hundred five patients with metastatic breast cancer were treated with 5-fluorouracil, Adriamycin, cyclophosphamide and BCG (FAC-BCG). The results were compared to those observed in a group of 44 patients treated with FAC chemotherapy alone. Although the overall response rates were similar (76% for FAC-BCG and 73% for FAC), the duration of remission was of 9 months for FAC and 14 months for FAC-BCG (p = 0.008). Similarly, survival of responding patients treated with FAC-BCG was significantly longer (24 months) than that observed in the chemotherapy alone treated group (15 months). There was no difference in survival or duration on study for nonresponders. Analysis of response rates by known prognostic factors was unrewarding. The duration of remission and survival, however, were significantly longer for patients with bone soft tissue involvement than for patients with visceral metastasis. Similarly patients with 1 or 2 metastatic sites survived significantly longer than those with more than 3 organ sites involved (p = 0.02). This chemotherapeutic combination is highly effective in inducing remissions. In addition, nonspecific immunotherapy with BCG appears to prolong duration of remission and survival for responding patients.

Adult↗
PubMed1979

Clinical evaluation of peptichemio.

Peptichemio is a peptide complex of m-L-phenylalanine mustard. A clinical evaluation of this agent was conducted in 116 patients, of whom 104 were evaluable for both toxicity and response. The majority of patients had solid tumors. The drug was administered iv daily for 3 days at doses of 20-75 mg/m2/day, with courses repeated at 3-4-week intervals. The optimal dose schedule appears to be 45 mg/m2/day for 3 days. The major side effects were cumulative myelotoxicity, phlebitis, and mild nausea and vomiting. No other major organ toxicity was observed. The partial remission rate was 7%. Most patients had received an alkylating agent as part of their previous therapy. There were seven partial responses and four less than partial responses achieved in patients with melanoma, lymphoma, and gastrointestinal, genitourinary, breast, and head and neck carcinomas. Responses lasted 4-36 weeks.

Adolescent↗
PubMed1979

Results of a phase II study of maytansine in patients with breast carcinoma and melanoma.

During the phase I study of maytansine at our institution, some activity was observed against breast carcinoma and melanoma. A phase II study was thus initiated to more thoroughly investigate the activity of this drug against these two tumors. In 33 evaluable patients with melanoma, no complete or partial responses were observed. Twenty-one evaluable patients with breast cancer were entered and only one response (partial) was seen. The toxicity was similar to that observed in the phase I study and consisted mainly of diarrhea, paresthesias, phlebitis, and flu-like symptoms. Myelosuppression was infrequent and was short-lived when it occurred.

Breast Neoplasms↗
PubMed1979

Phase I-II study of piperazinedione in adults with solid tumors and acute leukemia.

Piperazinedione was administered to 79 patients with solid tumors on an intermittent schedule with single doses of 1.5-36 mg/m2. Courses were usually repeated at 4-week intervals. Twenty-five patients with leukemia were treated at doses of 18-36 mg/m2 (occasionally for 2 successive days) every 1-4 weeks. Of 48 evaluable patients with malignant melanoma, three (6%) achieved partial remission and nine (20%) had stable disease. Eight of 17 (47%) patients with adenocarcinomas and one of two (50%) patients with lymphomas also had stable disease. Six of 14 (43%) patients with acute myelogenous leukemia showed hematologic improvement, as did one of 11 (9%) patients with blast cell crisis of chronic myelogenous leukemia. The principal toxic effect was myelosuppression, which occurred in 69% of the patients with solid tumors. Profound bone marrow aplasia occurred in 19% of the patients, resulting in six deaths (8%). Risk factors for marrow aplasia included extensive prior therapy, prior nitrosoureas, cumulative toxicity from piperazinedione, and abnormal liver function tests. The recommended doses for further studies are 9 mg/m2 for patients with risk factors for marrow aplasia, 12 mg/m2 for patients with prior therapy, 15 mg/m2 for previously untreated patients, and 24-36 mg/m2 for patients with acute leukemia.

Adult↗
PubMed1979

Penetration of 3-deazauridine into human brain, intracerebral tumor, and cerebrospinal fluid.

The antitumor agent 3-deazauridine (DAU) was administered rapidly to four patients before surgical removal of intracerebral tumor. Tumor, adjacent brain tissue, and temporalis muscle were assayed for DAU by high-pressure liquid chromatography. DAU penetrated comparably into tumor, brain, and muscle; in one patient, tissue concentrations were higher than concurrent plasma concentrations. The active metabolite 3-deazauridine 5'-triphosphate was quantitated in one tumor sample and greatly exceeded its Ki for cytidine 5'-triphosphate synthetase. DAU was also present in autopsy brain specimens from two patients treated shortly antemortem. Cerebrospinal fluid concentrations were 22.1 and 59.0%, respectively, of concurrent plasma concentrations during continuous infusion of DAU in two patients. Cerebrospinal fluid concentration was 3.1 microgram/ml 2 hr after a 30-min infusion of 1.5 g of drug per sq m and fell to 1.9 microgram/ml at 16 hr. Thus, DAU is capable of penetrating into intracerebral tumor, brain, and cerebrospinal fluid and is worthy of investigation in the treatment of intracerebral and meningeal neoplasms.

3-Deazauridine↗
PubMed1978

Adriamycin and 1-(2-chlorethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in the treatment of metastatic breast cancer.

Adriamycin every three weeks and CCNU every six weeks were given to thirty patients with metastatic breast carcinoma. Most patients had received prior chemotherapy. The overall response rate was 40%, with three patients obtaining complete remission. Survival was significantly prolonged in responders versus nonresponders. Three patients developed CNS metastasis while on treatment. Prior chemotherapy was a major factor in determining response rate; all patients without prior chemotherapy responded. The combination appears to be inferior to adriamycin alone in patients who have received prior chemotherapy.

Adult↗
PubMed1978

The value of adriamycin in the treatment of diffuse malignant pleural mesothelioma.

Thirty-six patients with diffuse malignant pleural mesothelioma were seen over a period of 15 years. The median age was 60 years (range, 21 to 75 years), and the male to female ratio was 2.3 to 1. The most common symptoms were chest pain and shortness of breath and all patients presented with pleural effusion on chest x-ray. The diagnosis was established by tissue biopsy in all cases. The median survival time for all patients was 12.5 months. Twenty-one patients were treated with an adriamycin-containing regimen and in this group, the median survival time from histological diagnosis was 14 months. In contrast, the median survival time for the 15 patients, who did not receive adriamycin, was 6 months (p = 0.009). The median survival time from the initiation of chemotherapy was 9 months for the adriamycin group and 2 months for patients treated with other type of chemotherapy (p = 0.001). Adriamycin appears to be of benefit in the treatment of diffuse malignant pleural mesothelioma.

Adult↗
PubMed1978

Sequential chemoimmunotherapy of colorectal cancer: evaluation of methotrexate, Baker's Antifol and levamisole.

Fifty-two untreated patients with colorectal cancer were randomized to receive 5-fluorouracil (5-FU) alternating either with methotrexate (MTX) or Baker's Antifol (BAF) with or without the immunostimulant, levamisole (Program I). Fifty-five patients who had received prior treatment were randomized to receive methyl-CCNU (Me) with MTX or BAF (Program II). Fifteen of these patients had failed to respond to initial therapy with 5-FU plus MTX or BAF and subsequently received Me plus the alternate antifol. Overall response rate for each of programs I and II was 10%. The responses were 1/11 with 5-FU-MTX plus levamisole, 2/12 with 5-FU-MTX, 1/8 with 5-FU-BAF plus levamisole, 0/8 with 5-FU-BAF, 2/20 with Me-MTX and 2/21 with Me-BAF. The median survival times (MST) for patients receiving Programs I and II were 10 and 5 months, respectively. The MST for all patients receiving MTX was significantly longer than that of patients receiving BAF Survival was not influenced by levamisole administration. Both chemotherapy programs were well tolerated. The sequential administration of 4 active agents failed to improve the results of treatment of colorectal cancer.

Adolescent↗
PubMed1978

Clinical, toxicological, and pharmacological studies of combination chemotherapy of adenocarcinoma with adriamycin and Baker's antifolate.

Ten patients with disseminated adenocarcinoma were treated with combination chemotherapy employing Adriamycin and Baker's Antifolate (BAF). There were seven patients with lung adenocarcinoma, two of whom achieved partial remission while the remaining five had their disease stabilized. Drug toxicity to the bone marrow, gastrointestinal mucosa, and skin was dose-limiting and was greater than the known toxicities of the individual drugs. Pharmacological studies of both drugs were performed on five patients to determine whether abnormal pharmacokinetics could explain this collateral toxicity. Adriamycin plasma concentrations and disappearance seemed to be unaffected by BAF. However, BAF levels were prolonged, apparently due to an Adriamycin effect on the plasma elimination of BAF, resulting in a prolonged exposure of sensitive tissues and organs to BAF. Consequently, when BAF and Adriamycin are used in combination, appropriate dose and schedule changes must be made to avoid any potentially serious side effects.

Adenocarcinoma↗