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Biomedical subjects

F A Shepherd

Publications and source records attributed to F A Shepherd.

At least 127 records · Page 7Linked to original sources
PubMed1986

Superior vena caval obstruction syndrome in small cell lung cancer.

In a series of 643 patients with small cell lung cancer (SCLC), 55 patients (8.6%) had signs or symptoms of superior vena caval obstruction syndrome (SVCO). Relatively long intervals from the onset of the first symptoms of SVCO to the start of therapy were observed, and invasive diagnostic procedures were safely performed in most patients. The pretreatment characteristics of patients with SVCO were not significantly different from those of patients without signs of the syndrome, and survival was similar in both groups. Patients with SVCO were usually treated first with induction chemotherapy, and prompt resolution of signs and symptoms occurred in the majority. Radiation was effective in controlling SVCO at relapse or after failure of initial chemotherapy. It was concluded that SVCO in patients with SCLC should be treated initially with systemic chemotherapy, as for other presentations of this disease. The current data do not support the commonly held view that SVCO in SCLC should be approached as an oncologic emergency.

Adult↗
PubMed1986

Methyl-CCNU and methotrexate therapy in patients with advanced colorectal cancer after failure of 5-fluorouracil chemotherapy.

Thirty-six patients with advanced colorectal cancer whose disease progressed during treatment with 5-fluorouracil (5-FU) chemotherapy were treated with methyl-CCNU and methotrexate. Five patients (14%) achieved a partial response (PR), three (8%) showed disease regression less than that required for a PR, and three (8%) showed evidence of stable disease. Twenty-five patients (69%) progressed on treatment. Tumor regression was seen only in patients with good performance status (ECOG 0.1). The median survival time of patients achieving a PR was 31 weeks. Those patients with stable disease or disease regression less than a PR had median survival times of 49 and 32 weeks, respectively. The comparable figure for those patients with disease progression was 17 weeks. Myelosuppression, principally in the form of leukopenia and thrombocytopenia, was common. Nausea and vomiting were universal with methyl-CCNU, and mucositis and diarrhea occurred commonly due to methotrexate. These results demonstrate the limited activity of chemotherapy in refractory colorectal cancer. They also reaffirm that poor pretreatment performance status should exclude patients from futile attempts at palliative therapy or phase II clinical trials, as these patients derive little or no benefit from them.

Adult↗
PubMed1986

5-Fluorouracil, adriamycin, and mitomycin-C (FAM) in the treatment of inoperable adenocarcinoma of the lung.

Fifty-three patients with inoperable adenocarcinoma of the lung were treated with 5-fluorouracil, Adriamycin, and mitomycin-C (FAM) in two dose schedules: schedule 1--5-FU 600 mg/m2 days 1, 8, 29, and 36 and Adriamycin 30 mg/m2 days 1 and 29 and mitomycin-C 10 mg/m2 day 1 repeated every 8 weeks. Schedule 2--5-FU 600 mg/m2 and Adriamycin 30 mg/m2 days 1 and 22 and mitomycin-C 10 mg/m2 day 1, repeated every 6 weeks. There were 28 males and 25 females, median age 57 years. There were 11 patients with limited disease and 42 patients with extensive disease. Ten patients had ECOG performance status 0; 34, 1; 6, 2; and 3, 3. Ten patients (18.8%) achieved a partial response. Response was seen in four limited disease patients (36.3%) and only six extensive disease patients (11.9%). The median duration of response was 33 weeks (range 17-50 weeks), and the median survival of these patients was 89.7 weeks. Sixteen patients achieved stable disease with a median response duration of 22 weeks (range 8-91 weeks). The median survival of the entire group was 32.6 weeks. The FAM regimen was tolerated well, with only mild gastrointestinal symptoms and moderate myelosuppression. The granulocyte nadir was less than 1,000 in 8% of patients and 1,000-1,500 in 20%. Only 5% of patients had a platelet count under 100,000 and three patients required red cell transfusions during treatment. These results indicate that FAM chemotherapy may be administered as an outpatient with minimal toxicity and can cause objective tumor regression in patients with adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1986

Is bone marrow examination in small-cell lung cancer really necessary?

Of 403 patients with small-cell lung cancer, we identified by aspiration, biopsy, or both 67 with bone marrow involvement and found the two procedures to be complementary in detecting marrow involvement. The mean surface area of the positive biopsy specimens was significantly greater than that of a randomly selected group of negative biopsy specimens, suggesting that the larger the specimen, the greater the chance of detecting tumour. Patients with marrow involvement had only a slightly worse prognosis compared with other patients who had extensive disease. Only 7 of the 403 patients (1.7%) had extensive disease based on marrow involvement alone. Because bone marrow examination rarely changes the stage of cancer in noninvasively assessed patients, and has no impact on the tolerance of chemotherapy and only a small effect on length of survival, we do not recommend this procedure in the routine staging of small-cell lung cancer.

Biopsy↗
PubMed1986

The relationship between 2-5A synthetase levels and persistent lymphadenopathy in homosexual men with antibodies to HTLV-III.

This study compared clinical and laboratory parameters in 37 individuals with serologic evidence of exposure to human T-cell lymphotropic virus type 3 (HTLV-III) and generalized lymphadenopathy. Basal levels of the interferon-induced enzyme, 2-5A synthetase were also measured and compared with the clinical parameters. A significant linear relationship (p less than .05) was demonstrated between the logarithm of the basal synthetase level and both the number and size of palpable nodes in the posterior cervical triangles of the men studied. No other lymph node chains demonstrated such a relationship. In addition, men with more than 3 palpable nodes (the median number) in the posterior triangles had lower mean levels of lymphocytes, reduced mean mitogen responses to PWM, PHA, and ConA, elevated mean levels of IgG, IgA, and IgM, and were more frequently anergic on skin testing. These findings suggest the need for further longitudinal study of the possibility that extent of lymphadenopathy and level of 2-5A synthetase might serve as useful parameters to monitor disease activity.

2',5'-Oligoadenylate Synthetase↗
PubMed1986

Therapy-related leukemia and myelodysplasia in small-cell lung cancer. Report of a case and results of morphologic, cytogenetic, and bone marrow culture studies in long-term survivors.

The bone marrow of 11 patients with small-cell lung cancer, who survived more than two years following combined-modality therapy, was subjected to morphologic, cytogenetic, and bone marrow culture studies. One patient, after a prodrome of anemia and thrombocytopenia, developed acute leukemia 60 months after the start of chemotherapy. Four months before frank leukemia developed, bone marrow culture studies showed a marked inability to form colonies. Cytogenetic studies demonstrated an abnormal clone of cells that included the deletion of the long arm of chromosome 5. No morphologic abnormalities were noted in the bone marrow of any other long-term survivor; however, the mean corpuscular volume of peripheral red blood cells was greater than normal in three of four patients who remain alive and disease free. In one of these patients marrow culture studies also failed to grow colonies. The other patients showed a decreased ability to form multilineage colonies and colonies of the granulocyte-macrophage lineage in vitro compared with a control population. All patients showed some degree of aneuploidy on cytogenetic analysis; in two cases approximately 50% of cells were aneuploid. However, no clonal abnormality was detected in any patient. Follow-up for the development of secondary acute leukemia and other long-term complications continues in these patients.

Aged↗
PubMed1986

First-line therapy with VP-16 and cisplatin for small-cell lung cancer.

VP-16 and cisplatin were used as first-line therapy in 31 patients with small-cell lung cancer (SCLC) in whom chemotherapy regimens that contained doxorubicin (Adriamycin [Adria Laboratories, Columbus, Ohio]) were contraindicated because of severe cardiac or hepatic disease. Eight patients who had cerebral metastases at presentation were also included in the study. There were 11 patients with limited disease (LD) and 20 with extensive disease (ED). Of the 28 evaluable patients, 12 (43%) had a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) failed to respond. The median duration of response (MDR) for LD patients was 39 weeks and for ED patients was 26 weeks. Patients with LD who responded (CR and PR) had a median survival time (MST) of 70 weeks (range, 28 to 232+ weeks), whereas ED patients who responded had an MST of 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. Mild degrees of reversible nephrotoxicity occurred in 15 patients, but required discontinuation of cisplatin in only two. The results of this study are compared with several other recently published reports of VP-16 and cisplatin used as first-line therapy in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Ketoconazole. Use in the treatment of ectopic adrenocorticotropic hormone production and Cushing's syndrome in small-cell lung cancer.

Recently, ketoconazole, an imidazole derivative with antifungal properties, has been shown to inhibit adrenal corticosteroid and androgen production. We treated a patient with small-cell lung cancer and Cushing's syndrome secondary to ectopic secretion of adrenocorticotropic hormone in whom it was necessary to discontinue chemotherapy. The patient was treated with ketoconazole, with a resultant reduction in urinary free cortisol and ketosteroid excretion and improvement in electrolyte balance. Ketoconazole may be a useful adjunct in the treatment of small-cell lung cancer or other malignancies associated with excessive corticosteroid production or as a hormonal therapy in breast or prostatic cancer.

17-Ketosteroids↗
PubMed1985

Elevated levels of interferon-induced 2'-5' oligoadenylate synthetase in generalized persistent lymphadenopathy and the acquired immunodeficiency syndrome.

The levels of the 2'-5' oligoadenylate enzyme synthetase in extracts of peripheral blood mononuclear cells from individuals with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) were measured and compared with synthetase levels in peripheral blood mononuclear cells (PBMs) from healthy heterosexual and homosexual controls. The mean basal synthetase level in heterosexual and homosexual controls was 14 +/- 13 and 12 +/- 9 pmol per hr/10(5) PBMs, respectively. Thirteen individuals with AIDS had a mean basal level of 129 +/- 75 pmol. Serial levels were persistently elevated in six of these individuals over a one- to 10-month period. Twelve of the 13 individuals had antibodies to human T cell lymphotrophic virus-III/lymphadenopathy-associated virus (HTLV-III/LAV). Thirty-three individuals with ARC had a mean basal synthetase level of 68 +/- 84 pmol. Thirty-two of the 33 had antibodies to HTLV-III/LAV. Eleven (33%) have had consistently normal synthetase levels (less than 2 SD above the mean for the homosexual controls, i.e., 30 pmol) over a three- to nine-month follow-up period. Fourteen (42%) had persistently elevated levels over the same period; four (29%) of these developed AIDS during the follow-up period. Eight have had fluctuating levels but have remained clinically well. These studies suggest that persistently elevated synthetase levels in individuals with ARC and antibodies to HTLV-III/LAV indicate progressive virus-induced disease activity. Elevated synthetase levels may be an important prognostic indicator of increased risk of progression to AIDS.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer.

Seventy-eight patients with evaluable small-cell lung cancer (SCLC) were treated with etoposide (VP-16) and cisplatin after their disease failed to respond to, or relapsed after, induction combination chemotherapy, consisting primarily of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV). Twenty-four patients had limited disease (LD) and 54 had extensive disease (ED). In six (8%) patients, a complete response (CR) was achieved and in 37 (47%), there was a partial response (PR). The median duration of response for responding patients was 22 weeks (range, 4 to 50 weeks) for patients with LD and 18 weeks (range, 4 to 49 weeks) for those with ED. Twelve percent of patients demonstrated stable disease, and 33% of patients had progressive disease on treatment. The median survival times of LD patients achieving a CR or PR were 59 and 34 weeks, respectively, whereas the comparable figures for ED patients were 45 and 23 weeks, respectively. Gastrointestinal toxicity was mild, but myelosuppression, predominantly leukopenia and thrombocytopenia, was common. Mild to moderate nephrotoxicity occurred in 11 patients, but was reversible in all cases. Two febrile episodes occurred during periods of drug-induced neutropenia, but no other significant toxicities were identified. These results provide further evidence that VP-16 and cisplatin is an effective and tolerable combination chemotherapy regimen for SCLC resistant to CAV.

Adult↗
PubMed1985

Carcinoembryonic antigen: a useful prognostic marker in small-cell lung cancer.

Plasma carcinoembryonic antigen (CEA) was determined in 180 patients with small-cell lung cancer (SCLC) before treatment. An abnormal level (greater than or equal to 6 ng/mL) was found in 34% of patients tested. Patients with extensive disease (39/83) had a significantly higher frequency of abnormal CEA (P = .001) than those with limited disease (22/97). There was a strong correlation between obtaining an objective response--particularly a complete response (P = .00003)--and the absence of an elevated CEA. Patients with an abnormal CEA also had a shorter survival time (P = .0007) and the difference remained statistically significant after logrank adjustment for extent of disease and ECOG (Eastern Cooperative Oncology Group) performance status. There was also a negative correlation between survival time and the quantitative level of CEA. In this series, only the group of patients with normal initial CEA levels included all survivors beyond 2.5 years. We conclude that CEA is a useful prognostic factor in SCLC.

Adult↗
PubMed1985

VP-16 and cisplatin as first-line therapy for small-cell lung cancer.

Thirty-one patients with small-cell lung cancer (SCLC) were treated with VP-16 and cisplatin as first-line therapy. In the majority of cases an Adriamycin (Adria Laboratories, Columbus, Ohio) containing regimen was contraindicated because of severe cardiac or hepatic disease. Eight patients who presented with cerebral metastases were also included in the series. Eleven patients had limited disease (LD), and 20 had extensive disease (ED). Of the 28 evaluable patients, 12 (43%) achieved a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) either had no response or progressed on treatment. The median duration of response for patients with LD was 39 weeks and for those with ED, 26 weeks. The median survival time (MST) for the whole group of responding (CR and PR) LD patients was 70 weeks (range, 28 to 181 + weeks), and for responding ED patients, it was 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. There were four febrile episodes during periods of drug-induced neutropenia and this led to one treatment-related death. Nephrotoxicity occurred in 15 patients and required discontinuation of cisplatin in two. These results compare favorably with reports of standard induction chemotherapy regimens and provide further evidence of the activity of the VP-16 and cisplatin regimen in patients with SCLC.

Adult↗
PubMed1985

Combination chemotherapy with bleomycin, etoposide, and cisplatin in metastatic non-small-cell lung cancer.

Fifty-three patients with recurrent and advanced stage (III and IV) non-small-cell lung cancer (NSCLC) were treated with a combination of bleomycin, etoposide (VP-16-213), and cis-diamminedichloroplatinum (BEP). Forty-eight patients were appraisable for response. The response rates were 44% for the entire group, 57% in 30 patients with combined squamous-cell and large-cell carcinoma, and 22% in 18 patients with adenocarcinoma (40%, 50%, and 19%, respectively, if patients not appraisable for response are included as nonresponders). The median survival time of patients with squamous-cell and large-cell carcinoma was slightly longer than that of patients with adenocarcinoma (23 weeks v 19 weeks). Patients with responsive disease survived significantly longer (median, 34 weeks) than did patients with unresponsive disease (median, 16 weeks) (P = .001). In the entire group, the median survival time of patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 was better (23 weeks) than of those with a status of 2 or 3 (15 weeks), but this difference was not seen in the subgroup with squamous-cell and large-cell carcinoma (24 weeks v 23 weeks, respectively). Thus, the performance status was not of prognostic value in the histologic subgroups experiencing the best response rate. There were two treatment-related deaths, but otherwise the toxicity of BEP was acceptable. Only four of the 119 treatment cycles were followed by fever even though there was significant neutropenia (0.5 X 10(9)/L) after 20 of 97 treatment cycles. The majority of patients receiving BEP experienced relief of cough, hemoptysis, pain, and fatigue associated with their disease. There was a good correlation between objective responses and palliation of symptoms. Thus, BEP offers good palliation, particularly for patients with squamous-cell and large-cell lung cancer.

Adenocarcinoma↗
PubMed1985

Tetracycline sclerosis in the management of malignant pericardial effusion.

Twenty-two patients with malignant pericardial effusion were seen at the Toronto General Hospital between 1979 and 1984. Under ECG monitoring, an indwelling Kifa catheter was inserted into the pericardial sac and then connected to a Hemovac system and allowed to drain for 12 to 24 hours. Xylocaine hydrochloride, 100 mg, was first instilled intrapericardially, followed by tetracycline hydrochloride, 500 to 1,000 mg, dissolved in 20 mL normal saline. The catheter was clamped for one to two hours and then allowed to drain into the Hemovac. This procedure was repeated every 24 to 48 hours until the net drainage was less than 25 mL/24 hours. Nine men and 13 women were treated (median age, 55 years). The primary malignancy included lung in 15 patients, breast in two patients, and carcinoma of the stomach, ovary, pleural mesothelioma, chronic granulocytic leukemia, and adenocarcinoma of unknown primary in one patient each. Twenty patients received one to five instillations of tetracycline. In one patient the catheter could not be inserted into the pericardial sac, and in one patient the catheter clotted before tetracycline instillation. Minor complications included transient arrhythmia in two patients, postinjection pain in four patients, and self-limited temperature elevation greater than 38.5 degrees C in two patients. fifteen patients had good control of their malignant pericardial effusion for more than 30 days (median survival, 160 days; range, 38 to 275 days). Three patients died before 30 days without evidence of effusion, and no patient surviving longer than 30 days developed recurrent effusion or pericardial constriction. Intrapericardial tetracycline instillation is a safe and efficacious treatment for malignant pericardial effusion and should be considered the first treatment modality in this situation.

Adult↗
PubMed1985

Limited impact of total parenteral nutrition on nutritional status during treatment for small cell lung cancer.

During a randomized trial of total parenteral nutrition (TPN) in patients with small cell lung cancer, we evaluated the short- and long-term effects of 4 weeks of TPN on nutritional assessment parameters. All 119 patients who were accrued to the study received the same chemotherapy and radiotherapy protocol which extended over a 1-year period: 57 patients received TPN; and 62 served as controls. At base line, patients with greater than 5% pretreatment weight loss had significantly lower levels of serum albumin, total iron-binding capacity, and creatinine/height index. TPN administration led to a significant increase in mean caloric intake and weight compared with controls (P less than 0.0001). In the short-term study, body fat, as measured by triceps skinfold thickness, was maintained, and there was a small increase in arm muscle circumference. Serum albumin and hematocrit decreased but promptly returned to pretreatment levels when TPN was stopped. There were no long-term differences in any of the nutritional assessment parameters between the two groups.

Adipose Tissue↗
PubMed1985

Phase II evaluation of bisantrene in patients with advanced non-small cell lung carcinoma.

Fourteen patients with measurable non-small cell lung cancer, who had not received prior chemotherapy, were treated with the anthracene derivative bisantrene. Although treatment was well tolerated, no antitumor activity was observed and all but two patients demonstrated disease progression before the third course of chemotherapy. We conclude that bisantrene does not have significant antitumor activity in non-small cell lung cancer.

Adult↗
PubMed1984

AIDS in a patient with hemophilia receiving mainly cryoprecipitate.

A 25-year-old man with hemophilia who had been treated primarily with cryoprecipitate presented with epigastric pain and loose, melenic stools. He had a long history of malaise and intermittent upper respiratory tract infection with fever. The patient was shown to have disseminated histoplasmosis and refractory herpes simplex. Immunologic studies demonstrated a markedly decreased ratio of helper to suppressor T cells, lymphopenia, cutaneous anergy and a slightly elevated serum IgA level. These findings met the criteria for the diagnosis of acquired immune deficiency syndrome. In addition, antibodies to human T-cell leukemia virus were detectable in the serum.

Acquired Immunodeficiency Syndrome↗