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Biomedical subjects

S C Remick

Publications and source records attributed to S C Remick.

47 records · Page 3Linked to original sources
PubMed1992

Extrapulmonary and pulmonary small-cell carcinoma: tumor biology, therapy, and outcome.

Extrapulmonary small-cell cancer is a distinct clinicopathological entity from small-cell anaplastic carcinoma of the lung. Approximately 1,000 cases have been projected annually in the United States, which represents an overall incidence of between 0.1% and 0.4% of all cancer. Not surprisingly then, little information is available regarding the treatment of this disease, which presents a challenge to the clinician when it is regionally confined. The majority of patients with extrapulmonary small-cell neoplasms have only been treated with local modalities of therapy, surgery, radiation, or a combination of both. Prolonged survival is not infrequent, which is in contrast to the experience for small-cell lung cancer and surprising given our current systemic approach to patients with this disease. This report will summarize the similarities and differences in biology, natural history, and clinical characteristics of patients with extrapulmonary small-cell cancer and small-cell anaplastic carcinoma of the lung. The histogenesis of small-cell cancer is briefly reviewed. A general therapeutic approach to patients with small-cell lung cancer is reported. Lastly, recommendations for therapy of patients with regionally confined extrapulmonary small-cell cancer by primary site are outlined.

Carcinoma, Small Cell↗
PubMed1990

Phase I trial of 5-fluorouracil and dipyridamole administered by seventy-two-hour concurrent continuous infusion.

Forty-seven patients with advanced malignancies were treated with a concurrent 72-h continuous infusion of 5-fluorouracil (FUra) and dipyridamole. The FUra dose was escalated over the dose range of 185 to 3600 mg/m2/day for 3 days. Dipyridamole was administered in a fixed dose of 7.7 mg/kg/day for 3 days. A total of 155 courses of therapy were completed of which there were 31 paired courses of the combination and FUra alone, at the same dose of FUra and in the same patient. This was for purposes of analysis of pharmacokinetics and modulation of FUra toxicity by dipyridamole. Stomatitis was the dose-limiting toxicity experienced by patients entered into this trial. Myelosuppression was not a serious problem. Increasing FUra plasma concentration was associated with greater leukopenia and stomatitis. Dipyridamole did not appear to modulate the systemic toxicity of FUra. The pharmacokinetics of FUra were altered by the concurrent administration of dipyridamole. Dipyridamole promoted the total body clearance of FUra which resulted in lower mean steady-state FUra plasma concentrations when compared with courses of FUra alone administered at the same dose level. These differences were statistically significant over the course of the trial. For courses of the combination, FUra exhibited linear pharmacokinetics over the dose range studied. Total body clearance of FUra declined slightly at the higher dose levels, but the differences were not significant. For courses of FUra alone, total body clearance was significantly decreased above the dose level of 2300 mg/m2/day. At the maximal tolerated dose of FUra, 2300 mg/m2/day x3, mean steady-state FUra plasma concentration and total body clearance were 6.6 microM and 122 liters/h/m2, respectively, for courses of the combination. The corresponding pharmacokinetic parameters were 7.4 microM and 103 liters/h/m2 for courses when FUra was given alone. Further evaluation of the utility of this regimen and basis of these pharmacokinetic observations appear warranted.

Adult↗
PubMed1990

Primary central nervous system lymphoma in patients with and without the acquired immune deficiency syndrome. A retrospective analysis and review of the literature.

Twenty-two cases of PCL were reviewed, in which 9 patients had AIDS and 13 did not. A review of the literature identified 247 cases of AIDS-related PCL. Differences between patients with AIDS and immunocompetent PCL were noted in our series. AIDS-related PCL when compared to non-AIDS PCL in our series has the following notable clinical features: 1) significantly younger age at presentation, median age 34 versus 59 years; 2) significantly higher incidence of B symptoms, 44% versus 8%; 3) worse median performance status at presentation, 3 versus 1; and, 4) shorter median survival, 3 versus 10 months. Differences in performance status and survival, however, were not significant. AIDS-related PCL is further characterized by frequent (44%) ring-enhancing mass lesions on head CT scan, a finding that makes it clinically difficult to distinguish from toxoplasmosis. Median survival appears to be improved in the absence of opportunistic infection at time of diagnosis of PCL, 6 versus 2 months. The therapeutic approach to patients with PCL, with and without AIDS, is variable. Combined modality therapy may improve the survival in patients with non-AIDS PCL. Therapy for patients with AIDS-related PCL is tailored to the status of the individual and it is, therefore, difficult to make comparisons to non-AIDS PCL patients. AIDS patients are often too ill to tolerate aggressive surgery or systemic treatment and in this instance, radiotherapy alone may be an acceptable alternative. Nonetheless, overall survival for patients with AIDS-related and non-AIDS PCL remains poor.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Lung cancer in patients seropositive for human immunodeficiency virus.

The authors describe the clinical and radiographic findings of lung carcinoma in six patients infected with the human immunodeficiency virus (HIV). These patients were in a younger age group than is commonly associated with lung cancer. The radiographic findings included mediastinal adenopathy (n = 5), hilar masses with distal atelectasis (n = 3), parenchymal masses (n = 3), pleural effusions (n = 2), and pleural thickening (n = 1). Recognition of any of these findings should raise the diagnostic possibility of lung cancer in this group of younger patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Phase I trial of hepatic artery infusion of 5-iodo-2'-deoxyuridine and 5-fluorouracil in patients with advanced hepatic malignancy: biochemically based combination chemotherapy.

Eighteen patients with hepatic metastases primarily from colorectal carcinoma were treated on a phase I protocol employing hepatic artery infusion (HAI) of 5-fluorouracil (FUra) and 5-iodo-2'-deoxyuridine (IdUrd) via implantable infusion pump. Patients received a 14-day continuous HAI of 300 mg/day FUra. During days 8-14 of therapy, patients received IdUrd as a separate 3-h HAI daily x 7. Treatment cycles were repeated every 28 days. IdUrd was escalated from 0.1 to 2.86 mg/kg/day x 7. Myelosuppression and stomatitis were mild and not dose limiting. Hepatotoxicity was dose limiting and similar to that reported for 5-fluoro-2'deoxyuridine alone administered as a 14-day infusion every month. One patient developed a clinical picture consistent with sclerosing cholangitis and another had biopsy-proven cholestasis and triaditis. Catheter complications occurred in 7 of 18 patients. Plasma concentrations of FUra during the 7-day continuous HAI of FUra alone were consistently either undetectable or very low (less than or equal to 0.1 microM). At level 3 (1.0 mg/kg/day IdUrd) and beyond, measurable plasma concentrations of FUra, iodouracil, and IdUrd were found at the end of the daily 3-h infusion of IdUrd. The maximum tolerated dose of IdUrd as administered in this trial is 2.2 mg/kg/day x 7 and the recommended starting dose for further clinical investigation is 1.7 mg/kg/day x 7.

Animals↗
PubMed1989

Methotrexate and dipyridamole combination chemotherapy based upon inhibition of nucleoside salvage in humans.

We have carried out a clinical trial in 23 patients to determine whether dipyridamole modulates the clinical effect of methotrexate. This trial was based upon in vitro studies which indicate that dipyridamole potentiates the cytotoxic action of methotrexate through inhibition of thymidine salvage. Methotrexate was given as a bolus injection 24 h after initiation of a high dose dipyridamole infusion. The trial was designed so that methotrexate was escalated in individuals until toxicity occurred and then the methotrexate dose resulting in toxicity was repeated without dipyridamole. During the course of this study the methotrexate dose was escalated from 10 to 130 mg/m2. While individual patient tolerance varied, moderate to severe myelosuppression and/or mucositis occurred frequently in patients receiving the combination with methotrexate doses greater than or equal to 60 mg/m2. Ten of 10 patients who experienced moderate or severe toxicity with the combination had significantly less toxicity when treated with methotrexate alone. Dipyridamole did not increase toxicity by an alteration in methotrexate elimination. The potentiation of methotrexate by dipyridamole in these patients suggests that physiological thymidine levels are sufficient to perturb the clinical effects of methotrexate and that thymidine salvage may represent a mechanism for clinical resistance to methotrexate. These results also suggest that a high dose dipyridamole regimen can be used as a pharmacological approach to test the role of nucleoside membrane flux on the clinical action of other standard chemotherapeutic drugs. Phase II studies testing the clinical efficacy of this combination should use a methotrexate dose of 60 mg/m2 with a provision for methotrexate dose escalation based upon individual patient tolerance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Extrapulmonary small-cell carcinoma. A review of the literature with emphasis on therapy and outcome.

We report 18 patients with extrapulmonary small-cell carcinoma, which we regard as a distinct clinicopathologic entity. The natural history of this disease in some sites appears to differ from that of small-cell lung cancer. One patient with small-cell carcinoma of the esophagus was treated with combination chemotherapy and survived for 1 year. Another patient had ectopic adrenocorticotropic hormone production with small-cell carcinoma of the rectum. Two patients with small-cell bladder carcinoma are also reported in this series. Another patient with small-cell carcinoma in a cervical lymph node metastasis has survived more than 7 years after receiving radiation as the only modality of therapy. This case further substantiates the observations of others that extrapulmonary small-cell carcinoma may pursue an indolent course. Furthermore, in certain sites, local modalities of therapy may result in long-term survival or cure. This is particularly true for small-cell neoplasms of the head and neck region. An association between smoking and extrapulmonary small-cell carcinoma is postulated. The therapy and outcome of this disease is also discussed, with particular emphasis on the effectiveness of combined strategies of surgery, radiation, and chemotherapy.

Adult↗
PubMed1987

Phase II trial evaluating continuous infusion of etoposide, cisplatin, and hexamethylmelamine in extensive-disease small cell carcinoma of the lung.

A total of 27 untreated and 24 previously treated patients with extensive-disease small cell lung cancer (SCLC) were treated with a combination chemotherapeutic regimen of continuous-infusion etoposide for 5 days, cisplatin, and hexamethylmelamine. of 25 evaluable patients with untreated SCLC, three (12%) achieved a complete response and 16 (64%) achieved a partial response. Among 23 evaluable patients with relapsed SCLC there were no complete responses and nine (39%) achieved a partial response. Median survival times were 252 and 109 days for the above groups, respectively. Myelotoxicity, especially thrombocytopenia, was moderately severe. Other toxic effects, including renal and neurologic, were minimal. These results compare favorably with other regimens including etoposide and cisplatin. Our results further confirm the activity of etoposide and cisplatin as both initial therapy and as a salvage regimen in the management of patients with extensive-stage SCLC.

Adult↗