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Biomedical subjects

J H Saiers

Publications and source records attributed to J H Saiers.

At least 19 recordsLinked to original sources

Accuracy in equianalgesic dosing. conversion dilemmas.

The clinical benefit and increased application of opioid rotation has focused attention on efficacy differences between opioids and their respective equianalgesic dose ratios. Understanding the differences between the opioids is critical to understanding their equianalgesic dose ratios and for adjusting therapy following rotation to a new analgesic. The purpose of this article is to describe controversies regarding the relative potencies of these agents as presented in current equianalgesic charts and to provide pharmacologic information to assist the clinician with opioid rotation.

Analgesics, Opioid↗

Growth inhibition of human prostate tumor cells by an agonist of gonadotrophin-releasing hormone.

The effect of [D-Leu6,des-Gly-NH2(10),Proethylamide9]-GnRH, leuprolide, was determined for the human primary prostate tumor cell line ALVA-31 by in vitro mitogenic assays. Prostate tumor cell proliferation was inhibited up to 50% by leuprolide. Inhibition was not observed in parallel cultures treated with other low molecular weight bioactive peptides. The incorporation and metabolic reduction of testosterone was not affected by concentrations of leuprolide that were inhibitory in the mitogenic assay. Specific high-affinity binding of 125I-labeled leuprolide was also demonstrated on intact tumor cells with an estimated effective median dose (ED50) of < 1 x 10(-9)M. Inhibition of prostate tumor growth was further demonstrated in Balb/c athymic intact and castrate male mice bearing ALVA-31 tumor xenografts following chronic administration of leuprolide. These data clearly demonstrate that leuprolide can inhibit the growth of a human prostate carcinoma cell line. Studies conducted in castrate animals further suggest an alternative mechanism of growth inhibition that appears to be independent of the suppression of steroid hormone biosynthesis by LHRH analogues.

Animals↗

Phase II evaluation of merbarone in renal cell carcinoma.

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.

Antineoplastic Agents↗

Doxorubicin, mitomycin C and 5-fluorouracil in the treatment of hormone refractory adenocarcinoma of the prostate: a Southwest Oncology Group study.

In a Southwest Oncology Group phase II clinical trial, 68 patients with hormone refractory carcinoma of the prostate were treated with a combination of doxorubicin, mitomycin C and 5-fluorouracil. Of the patients 11 were classified as good risk and 57 as poor risk. There were 1 complete and 10 partial remissions for a response rate of 16.2% (exact 95% confidence interval 8.4 to 27.1%). Median survival was 9 months (maximum 14) for good risk patients and 10 months (maximum 42) for poor risk patients. Toxicity was significant with leukopenia identified as dose limiting. Because of the low rate of response and significant toxicity, this regimen cannot be recommended as standard therapy for metastatic hormone refractory prostate cancer.

Adenocarcinoma↗

Gallium nitrate in advanced bladder carcinoma: Southwest Oncology Group study.

Gallium nitrate is a heavy metal anticancer agent that has demonstrated widespread activity in a number of phase I studies. This phase II study employed a starting dose of 700 mg/m2 IV every two weeks in patients with advanced bladder carcinoma. Significant nephrotoxicity observed in 4 of the first 10 patients required extending the time between cycles to three weeks in the remaining 24 patients. One complete response and six partial responses were achieved. Nephrotoxicity was the major dose-limiting toxicity. Gastrointestinal toxicity and myelosuppression were minimal. Gallium nitrate appears to be an active agent in advanced carcinoma of the bladder. Further clinical trials with this agent are warranted.

Antineoplastic Agents↗

Defects in natural killer cell activity and interferon response in human lung carcinoma and malignant melanoma.

The natural killer (NK) activity of peripheral blood mononuclear cells from 25 patients with squamous cell carcinoma of the lung, malignant melanoma, or epitheloid cancers of the gastrointestinal tract was measured by the lysis of 51Cr-labeled K562 target cells. NK activities of many patients with lung cancer or malignant melanoma were decreased relative to normal controls. This abnormality was significantly correlated with advancing stage of disease and the percentage of monocytes in the cell suspensions. Addition of indomethacin or removal of monocytes did not restore depressed NK function to normal levels. Abnormalities of NK function did not appear to be secondary to the presence of mononuclear suppressor cells. The response to interferon was also impaired in patients with advanced disease. The number of effector:target conjugates was normal even in patients with depressed NK function; however, the number of active lytic effectors was decreased. These results imply that the cells which bind tumor targets are present in patients with advanced cancers, but these cells are either immature or functionally inactive.

Humans↗

Combination chemotherapy, radiotherapy, and BCG immunotherapy in extensive (metastatic) small cell carcinoma of the lung. A Southwest Oncology Group study.

From November 1976 to November 1978, the Southwest Oncology Group treated 254 patients with extensive (metastatic) small cell carcinoma of the lung with combination chemotherapy and radiotherapy with and without BCG immunotherapy. Patients receiving BCG achieved a response rate of 50% versus those patients not receiving BCG of 46% (P = .704). Response duration was 20 weeks for the BCG arms and 23 weeks for the no-BCG arms; survival was 28 weeks for the BCG arms versus 29 weeks for the no-BCG arms. An adverse effect in patients surviving more than one year was detected; those continuing to receive BCG had significantly shorter survival, 60 weeks versus 85 weeks (P = .019). Toxicities of the programs were not affected by the addition of BCG immunotherapy. It appears that BCG immunotherapy has no beneficial effect on response rate or duration of response in programs using chemotherapy and radiotherapy for control of metastatic small cell carcinoma of the lung. In addition, because of the adverse effect on long-term survival, we do not recommend the addition of BCG immunotherapy as a treatment modality in this tumor type.

Antineoplastic Agents↗

Suppressor leukocytes in anergic patients with solid tumors.

Anergic patients with solid tumors were studied for the presence of suppressor cells which could be responsible for their significantly impaired phytohemagglutinin induced lymphocyte proliferation. Three types of suppressor cell assays were measured. First, no increased activity of prostaglandin producing suppressor cells was found in 10 cancer patients. Second, 5 cancer patients did not have significantly increased activity of short-lived suppressor cells in comparison with normal subjects. Third, no enhanced activity of concanavalin A induced suppressor cells was seen in 6 patients. This study emphasizes that the in vitro T cell immunodeficiency in this group of cancer patients was not due to suppressor cells as measured by conventional in vitro assays and emphasizes the potential importance of a loss of responder cells or other suppressor mechanisms in immune deficient patients with solid tumors.

Adult↗

Chemotherapy trial with comp-F regimen in advanced adenocarcinoma of prostate.

Multiple agent combination chemotherapy was used to treat 16 patients with Stage D adenocarcinoma of the prostate in relapse. Agents employed were cyclophosphamide (Cytoxan), methotrexate, 5-fluorouracil, vincristine, and prednisone. Results were encouraging. Six of 16 patients achieved an objective response (2 complete, 3 partial, 1 stabilization) for a 37.5 per cent response rate. Eleven of 16 patients achieved a subjective response for a 69% response rate. Soft tissue metastases may be more responsive than bony lesions. Employment of vincristine made no obvious difference in response rate in those patients in whom it was used. Toxicity was only moderate. Further studies are warranted.

Adenocarcinoma↗