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Biomedical subjects

S G Taylor

Publications and source records attributed to S G Taylor.

At least 127 records · Page 7Linked to original sources
PubMed1984

Cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in women more than 65 years old with advanced breast cancer: the elimination of age trends in toxicity by using doses based on creatinine clearance.

Ninety-two patients with advanced breast carcinoma and no prior chemotherapy from 65 to 90 years old were treated with the combination cyclophosphamide (C), methotrexate (M), and 5-fluorouracil (F) (CMF). Because of the primary renal excretion of the first two drugs, their initial doses were calculated using a linear function of creatinine clearance. 5-Fluorouracil was given at 2/3 of the usual dose. These doses resulted in no significant age trends in almost all toxicity, response, time to failure, or cycle by cycle percentages of calculated dose actually received. There was significantly less nausea and vomiting as age increased (P less than .001) and patients greater than 80 years had a significantly shorter survival (P = .01) than patients aged 65 to 79 years. The toxicity results are in marked contrast to the experience of 126 patients aged 24 to 65 years treated with usual doses of CMF on earlier protocols. Among these younger patients there was a significant upward trend with age in diarrhea (P less than .001) and noticeable upward trends with age in hematologic toxicity (P = .06), infection (P = .06), and severe mucositis (P = .09). Patients greater than 65 years had their doses decreased less quickly than did patients less than 65 years; hence by the sixth cycle, the young and elderly patients were receiving almost the same amount of M and F.

Aged↗
PubMed1984

A randomized comparison of high-dose infusion methotrexate versus standard-dose weekly therapy in head and neck squamous cancer.

Forty-seven patients with recurrent or metastatic head and neck squamous cancer were entered into a prospectively controlled study comparing high-dose infusion methotrexate with leucovorin against standard-dose methotrexate without leucovorin. Patients were stratified for prior treatment and hematogenous metastases prior to randomization. Patients received either methotrexate (1,500 mg/m2) infused over 24 hours with leucovorin or 40 mg/m2 intramuscularly. Each treatment was given weekly for the first six weeks and followed a dose escalation schedule to toxicity. After six weeks patients received the high-dose regimen every two weeks and the low-dose schedule continued weekly. One patient was ineligible and four had inadequate follow-up to assess response (less than two weeks). Forty-two patients were evaluable for survival and 37 for response. Six of 19 patients (32%) treated with high-dose infusion responded (one complete response) and four of 18 patients (22%) receiving standard dosage responded (P = .52). Treatment with high-dose methotrexate resulted in an improved duration of disease control over standard dosage with the respective median times to progression of 11 weeks and five weeks (P = .04). These differences were most marked in good performance status patients (P = .007) and those without hematogenous dissemination (P = .02). Toxicity, however, was also significantly worse in the high-dose treatment group (P = .01) and survival was identical between treatments (4.2 months). The authors conclude that any treatment advantage to high-dose methotrexate may be attributable to its greater toxicity rather than to a selective therapeutic effect and this regimen does not result in improved patient survival. Good performance status patients may benefit from more aggressive therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Sequential methotrexate and 5-FU in CMFP (cyclophosphamide, methotrexate, 5-FU, and prednisone) therapy for breast cancer.

Forty-one women with advanced breast cancer were treated with cyclophosphamide, methotrexate, 5-FU, and prednisone. Methotrexate (200 mg/m2) was given iv 1 hour before administering 5-FU (600 mg/m2). Leucovorin (10 mg orally every 6 hours for six doses) was begun 24 hours after the methotrexate. The response rate was 43%, with 19% of patients having a clinically complete remission. This overall objective response rate is lower than that achieved when this drug combination is given at standard doses of methotrexate and with no interval before 5-FU. Toxicity was primarily related to bone marrow suppression; eight women had wbc counts that fell to less than 1500/mm3.

Adult↗
PubMed1983

A randomized trial of adjuvant BCG immunotherapy in head and neck cancer.

Fifty-two patients with locally advanced squamous cell cancer were entered into a randomized trial of BCG vaccine following definitive local therapy. Patients were stratified and randomized to receive BCG vaccine (25 patients) or no adjuvant immunotherapy (27 patients). The BCG vaccine therapy began two weeks following definitive therapy with 2 to 4 X 10(6) Tice strain BCG organisms given intradermally (ID) in alternating sides of the neck every two weeks six times, then every four weeks nine times. In addition, all patients received methotrexate prior to definitive therapy. Median duration of follow-up at the time of analysis was 41 months. Groups were balanced by sex, disease site and stage, histologic grade, and prior therapy. Thirteen (52%) of the BCG vaccine-treated group remain disease free v seven (26%) of the controls. Similarly, 17 (68%) of the BCG vaccine-treated group survived v 11 (41%) of the controls. We conclude regional ID BCG vaccine increases disease-free and actuarial survival in this study population and adjuvant immunotherapy should be further explored in ear, nose, and throat cancer.

Adult↗
PubMed1982

Antigen specificity of squamous cancers of the head and neck based on tumor site using the slide leukocyte adherence inhibition assay.

Patients with a diagnosis of squamous cancer of the upper aerodigestive (UAD) system were tested with extracts of squamous cancer arising from several regions of the UAD tract and compared to various control populations, using the slide leukocyte adherence inhibition (LAI) assay. Seven tumor extracts were tested. Twenty-five of 77 tests (32%) were positive in unselected UAD squamous cancer patients. However, matching patients with tumor extract by the site of origin within the UAD tract, 19 of 22 tests (86%) were positive when the site of origin was identical for leukocyte donor and extract. Two of four patients tested with an extract prepared from a different site with in the same region of the UAD system were positive; whereas only 4 of 51 tests (8%) were positive in patients tested with an extract from a cancer arising from a different region within the UAD tract (P less than 0.001). One of 33 tests using patients with either not cancer (11 tests), squamous cancer of other regions (15), or adenocarcinoma (7) reacted to the extracts of UAD tract cancers. We conclude that patients with squamous cancer of the UAD tract can recognize distinct tumor-associated antigens that are site-specific and are non-cross-reactive using the LAI technique.

Antigens, Neoplasm↗
PubMed1982

Lymphocyte responsiveness to thymosin in angioimmunoblastic lymphadenopathy with lymphomatous transformation.

Lymphocytes from a patient with angioimmunoblastic lymphadenopathy with lymphomatous degeneration were tested in vitro for thymosin responsiveness. The percentage of lymphocytes forming spontaneous (E) rosettes to sheep red blood cells (SRBC) was 37 and 32% in the absence of thymosin on two separate occasions. Lymphocytes incubated with thymosin formed rosettes in 55 and 43% when incubated with 0.1 micrograms/ml and 66 and 63% when incubated with 100 micrograms/ml, respectively. The patient subsequently received thymosin while in a preterminal condition. No clinical response to thymosin was apparent and lymphocytes tested 8 days after starting thymosin treatment demonstrated reduced thymosin responsiveness (31% without thymosin vs 37% with 100 micrograms/ml). The failure to respond clinically to thymosin treatment may be related to the preterminal condition. The in vitro responsiveness to thymosin suggests that thymosin effect should be examined earlier in the course of this disease process.

Aged↗
PubMed1982

PALA in advanced breast cancer. A phase II pilot study by the ECOG.

Thirty-three patients with advanced breast cancer were treated with PALA at a schedule of 1500 mg/m2/day for 5 days every 3 weeks. Time to progression varied from 4-305 days from the start of therapy (median, 49 days) with 3 partial responses (9%) for 231, 180, and 64 days, respectively. Toxicity was considerable, with severe skin and mucosal toxicity occurring in 48% and 39% of cases, respectively. Hematologic toxicity was usually mild. We conclude PALA has limited activity in advanced breast cancer, but may be of advantage in combination chemotherapy because of the relative bone marrow-sparing properties.

Adult↗
PubMed1982

TG cell involvement in the leukocyte adherence inhibition phenomenon.

Peripheral blood mononuclear cells (PBMC), T-cells, non-T-cells, TG cells, and TM cells were tested for leukocyte adherence inhibition (LAI) reactivity to purified protein derivative (PPD) in normal human volunteers to determine the reactive cell subfractions. T-cells were separated by sheep red blood cell rosetting and TM and TG cells by rosetting with anti-ox red blood cell (ORBC) IgM- and IgG-treated ORBC. Fresh PBMC, T-cells, and TG cells gave positive LAI reactivity to PPD in PPD-positive donors only. PBMC that had undergone 24-hour incubation or extensive washing, non-T-cells, and TM cells were unreactive. All cell subfractions were negative in PPD-negative donors. Indirect LAI assay was performed on the spent media from overnight incubation of unstimulated PBMC and also following a 1-hour incubation of the various cell subfractions obtained from a PPD-reactive donor with PPD. Positive reactions, indicating the release of an LAI factor (LAIF), were obtained with the spent media and with the T-cell and TG cell subfractions following PPD stimulation, whereas non-T-cell and TM cell subfractions yielded no reactivity. Incubation of sensitized T-cells with PPD in the presence of cycloheximide and preincubation of T-cells for 24 hours with cycloheximide before PPD exposure failed to inhibit LAI reactivity. These data suggest that T-cells, specifically TG cells, can release LAIF upon specific antigen stimulation with PPD, whereas non-T-cell and TM cell subpopulations fail to respond to the same stimulus. LAIF may also be released into the culture media with prolonged (overnight) incubation in artificial media or with extensive washing. Inhibition of protein synthesis during antigen exposure or up to 24 hours before antigen exposure does not appear to inhibit LAI reactivity.

Cell Separation↗
PubMed1981

Adriamycin, vincristine, dibromodulcitol, and hexamethylmelamine in advanced previously treated breast cancer: an ECOG pilot study.

A combination of adriamycin, vincristine, dibromodulcitol, and hexamethylmelamine was piloted in patients with advanced breast cancer who had failed prior CMFP chemotherapy, as a part of ongoing trials by the Eastern Cooperative Oncology Group to improve second-line chemotherapy for this disease. The vincristine was given as an intensive 5 week induction regimen and hexamethylmelamine was administered on days 15-27 of a 28 day cycle, at the time of anticipated nadir peripheral blood counts. The study was terminated early after only 9 patients had been entered because of severe neurotoxicity related to the intensive schedule of vincristine as well as hematologic and gastrointestinal side effects. Three patients responded for 11, 18 and 21 weeks. The limited therapeutic benefit did not justify the toxicity produced, and suggested that intensive dosage schedules of vincristine, and use of low dose hexamethylmelamine during the time of anticipated hematologic nadir counts would not be of substantial benefit.

Aged↗
PubMed1980

Chemotherapy for squamous cell carcinoma of the head and neck: a progress report.

This review highlights the most important recent advances in the chemotherapeutic management of patients with squamous cell carcinoma of the head and neck. Previous chemotherapy trials must be interpreted with caution in the absence of information concerning important prognostic variables, such as prior treatment, nutritional and performance status, and the heterogeneity of primary sites. In patients who have recurrent or metastatic disease, methotrexate, platinum, and bleomycin are three active drugs when used as single agents. There is no evidence that high dose methotrexate therapy is superior to more conventional weekly intravenous administration of methotrexate in the treatment of recurrent disease. Platinum is a new agent that has demonstrated activity against hematogenous as well as regional disease. In the absence of evidence of a dose-response curve for platinum, the lower dosage schedules that can be used with acceptable toxicity on an outpatient basis should be selected. Combination chemotherapy has resulted in a high proportion of objective responders and approximately 20 per cent complete remissions with any of several platinum containing regimens. However, the median duration of response remains short, and none of the combination drug programs has as yet been established to be superior to single agent chemotherapy in a randomized trial. Both single agent and combination chemotherapy programs have been used prior to initial surgery or radiation in patients with advanced inoperable but nonmetastatic disease. Despite dramatically higher response rates over those obtained with the same drugs used in recurrent disease, there is as yet no evidence that chemotherapy given in this manner has resulted in improved disease free or overall survival compared with local treatment alone. Similarly, the use of adjuvant chemotherapy following tumor clearance to eradicate potential micrometastatic disease is currently under investigation and cannot be recommended in the absence of a controlled trial. This article reviews the clinical trials currently in progress both for patients with recurrent squamous cell carcinoma of the head and neck and those with advanced local or regional disease.

Antineoplastic Agents↗
PubMed1979

A randomized comparison of two dosage schedules of methyl CCNU: three-week versus six-week treatments.

Two dose schedules of methyl CCNU were compared for drug effect and toxicity. One hundred thirteen patients were stratified by tumor site, performance status, and prior chemotherapy and randomized to 100 mg/m2 q 3 wk or 200 mg/m2 q 6 wk orally. Response rates were similar (12% vs. 18%, respectively, in the major tumor sub-types studied) and survival was equivalent. Hematologic toxicity, however, was significantly different, with earlier time to the most severe blood count depressions, more frequent occurrence of severe depression, and a larger percentage of patients requiring dosage reduction on the 6-week regimen. We conclude that the 3-week regimen is superior due to its improved tolerance and is recommended especially for combination drug therapy.

Adenocarcinoma↗
PubMed1979

Bleomycin in combination chemotherapy of metastatic Wilms tumor: a late recurrent case, refractory to conventional therapy.

A patient with a late recurrence (13 years) of Wilms tumor is presented. After relapse with conventional chemotherapy, an objective partial remission was obtained with bleomycin, vinblastine, cyclophosphamide, and cis-platinum. Stable disease was noted when bleomycin was withheld. Bleomycin in this combination appeared to effect a good response, and further studies of chemotherapy of Wilms tumor should include bleomycin in combination with other active agents.

Antineoplastic Agents↗
PubMed1978

Adjuvant methotrexate and leucovorin in head and neck squamous cancer. Two-year follow-up of a pilot project.

A series of 17 patients with stage III and IV head and neck cancer received three cycles of methotrexate and leucovorin calcium during an interval of two weeks prior to surgery and/or radiotherapy. The dosage of methotrexate was sequentially escalated to produce mucositis (the usual dose-limiting toxicity). All patients have been followed up for a minimum of two years (range, 24 to 44 months). Two recurrences and two second primary tumors occurred in seven patients with stage III cancer, and one recurrence and one postoperative death (pulmonary embolism) occurred in ten patients with stage IV cancer. Seventy-six percent of patients survived, with 71% disease free. Mucositis occurred in 88% but was transient and prevented oral fluid intake in only one patient. Bone marrow suppression was usually mild and did not delay surgery. Escalation of dosage was thought to be important in achieving these encouraging results. A controlled trial is under way to better define the degree of efficacy of this regimen of adjuvant chemotherapy.

Adult↗