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Biomedical subjects

J D Ahlgren

Publications and source records attributed to J D Ahlgren.

36 records · Page 2Linked to original sources
PubMed1989

Intraperitoneal chemotherapy complicated by erosion of a Tenckhoff catheter into the colon.

Insertion and maintenance of intraperitoneal catheters must be done with meticulous attention to detail. We recommend insertion under direct vision to minimize the incidence of intestinal perforation during catheter placement. Intraperitoneal catheters should not be placed in close proximity to a fresh intestinal anastomosis because this position may promote anastomotic dehiscence. Communication between the catheter and the intestinal lumen necessitates catheter removal.

Catheters, Indwelling↗
PubMed1989

A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study.

One hundred seventy-nine patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to compare two schedules of delivery for single-agent fluorouracil (5-FU). The "standard" treatment was a schedule commonly employed in clinical practice, namely, a daily bolus dose administered intravenously (IV) for five consecutive days and repeated at 5-week intervals. The investigational treatment was a continuous infusion of 5-FU administered 24 hours a day for a protracted time (10 weeks or more). Both treatments were continued until the development of disease progression or unless interrupted for toxicity. Using stringent objective criteria requiring independent confirmation of x-ray or scan-documented response, the tumor response rate reached 7% (six of 87) for the bolus arm and 30% (26 of 87) for the infusion arms (P less than .001). Toxicity was substantially different for the two arms with major leukopenia observed only on the bolus arm, 22% developing grade 3 (severe) or grade 4 (life-threatening) leukopenia with four sepsis-related deaths. Hand-foot syndrome was observed only in the infusional arm, requiring treatment interruptions and dose reductions in 24% of patients, but with little impact on quality of life. In spite of the major difference in objective response rate, overall survival for the two groups was comparable. Administration of 5-FU as a continuous infusion for protracted periods clearly improves the therapeutic index for this agent in patients with advanced colon cancer with respect to response rate and reduced toxicity. This schedule appears workable in the community setting and yields response rates similar to those reported for 5-FU with high-dose leucovorin, but without the gastroin testinal toxicity profile of the latter combination.

Adenocarcinoma↗
PubMed1989

Cochleovestibular toxicity related to dichloromethotrexate.

A 69-year-old man receiving monotherapy for lung cancer with dichloromethotrexate (DCM), and without exposure to other chemotherapeutic agents or known ototoxic drugs, developed profound cochleovestibular dysfunction. The initial presentation was vestibular. This resolved, but unilateral hearing loss ensued and continued to progress to a total of 80 db loss in the low frequency range and 40 db in the high range, despite discontinuation of the drug. Because DCM may be used in combination with the known ototoxin cisplatin, the potential of DCM as an ototoxin should also be considered in such patients.

Aged↗
PubMed1986

5-fluorouracil, adriamycin, and mitomycin in the treatment of adenocarcinoma of unknown primary.

The combination of 5-fluorouracil (5-FU), doxorubicin, and mitomycin (FAM) is often recommended for empiric management of patients with adenocarcinoma of unknown primary. This recommendation is based on the activity of FAM for adenocarcinomas of specific known sites of origin. A literature search disclosed no reports of the efficacy of FAM in this clinical entity. We report on 45 patients with biopsy-proven adenocarcinoma in whom investigation revealed no primary site and who were treated in a phase II trial with FAM. Of 43 evaluable patients, four achieved a complete tumor response, and nine obtained a partial response for an overall response rate of 30%. The median survival for all patients was greater than 10 months. The median survival for patients whose tumors were unresponsive to FAM was 6 months, and median survival was greater than or equal to 14 months in patients with stable disease or FAM-responsive tumors. A phase III trial comparing no therapy or 5-FU with FAM is warranted. For patients not treated in an investigative setting, FAM compares favorably with reported series using other regimens.

Adenocarcinoma↗
PubMed1985

Phase I study of echinomycin administered on an intermittent bolus schedule.

We have conducted a phase I study of the cyclic peptide echinomycin (Quinomycin A) on a schedule of administration of once every 4 weeks. Ten dose levels between 20 and 1800 micrograms/m2 were studied. Acute gastrointestinal toxicity, thrombocytopenia, and transient elevations of serum transaminases occurred at doses of greater than or equal to 1000 micrograms/m2. Gastrointestinal toxicity was severe and dose-limiting in several patients at doses of 1800 micrograms/m2. Thrombocytopenia was erratic, but generally increased with drug doses. Platelet count nadirs occurred 5-10 days after administration. Hepatic toxicity was reflected in transient elevations of serum transaminases without hyperbilirubinemia. Three patients experienced apparent anaphylactic reactions to doses of 1500 micrograms/m2. The maximum tolerated single dose of echinomycin was 1800 micrograms/m2. A starting phase II dose of 1500 micrograms/m2 is recommended.

Adult↗
PubMed1984

A Phase II trial of high-dose intravenous interferon alpha-2 in advanced colorectal cancer.

Twenty-one patients with metastatic colorectal cancer were treated with high-dose intravenous interferon alpha-2 (30-50 X 10(6) units/m2) administered daily for 5 consecutive days. Courses of therapy were repeated every 2 to 3 weeks. No tumor responses were seen among 15 evaluable patients. In two subjects, disease remained stable for 3 and 7 months, respectively. Toxicity was substantial and a de-escalation of dose was frequently required. Fevers, gastrointestinal symptoms, fatigue, leukopenia, and elevated serum transaminases were common. High-dose interferon was found to be ineffective in the treatment of metastatic colorectal cancer. A daily dose of 50 X 10(6) units/m2 was greater than the maximum tolerated dose in this group of patients.

Adult↗
PubMed1984

A Phase I trial of spirogermanium administered on a continuous infusion schedule.

We have evaluated the toxicity of the antitumor agent spirogermanium on a schedule of continuous intravenous administration for periods up to five days. The doses tested were between 100 mg/m2/day and 500 mg/m2/day. Peripheral vein phlebitis occurred at all dose levels and was not relieved by addition of hydrocortisone or heparin to the infusion. No phlebitis occurred when the drug was administered through a central vein. The dose limiting toxicity of spirogermanium was neurologic, notably tremors and mental confusion. These problems became progressively more severe at doses above 250 mg/m2/day. There was no discernible bone marrow, renal or hepatic toxicity. One patient developed reversible interstitial pneumonitis. The recommended Phase II dose of spirogermanium is 200 mg/m2/day for five days, with the possibility of escalation in selected patients. Because spirogermanium is more toxic to tumor cells with prolonged exposure than with intermittent exposure, this schedule could be considered for Phase II trials, particularly in diseases thought to be especially sensitive such as ovarian and prostatic carcinoma or lymphomas.

Adult↗
PubMed1982

Current management of advanced and locally unresectable gastric carcinoma.

Gastric cancer is the most chemotherapy-responsive adenocarcinoma of the major gastrointestinal sites. For patients with advanced disease, the response rates and survival achieved with recently designed Adriamycin-based regimens represent an improvement over the past use of 5-fluourouracil alone or combined with a chloroethylnitrosourea. Effective palliative treatment can be administered in an out-patient setting without the necessity of producing severe or life-threatening toxicity. Nevertheless, response durations are finite, as is patient survival. It is essential that Phase II trials of new drugs be continued in an attempt to identify agents with greater therapeutic activity for this disease. For the locally unresectable stage, combined modality therapy incorporating palliative resection of the primary tumor, regional radiation therapy and chemotherapy, has provided long-term disease-free survival for 15--25% of all patients. The most promising aspect of current clinical investigation is the application of the Adriamycin-based drug combinations in controlled trials of surgical adjuvant therapy.

Antineoplastic Agents↗
PubMed1982

Repair of DNA alkylation induced in L1210 leukemia and murine bone marrow by three chloroethylnitrosoureas.

The removal of DNA adducts is an essential step of DNA repair following exposure to chloroethylnitrosoureas. Adduct removal was evaluated in both L1210 and murine bone marrow DNA for lesions induced by three chloroethylnitrosoureas. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea, a marrow-toxic agent with high carbamoylating activity, was not removed in either system for at least 6 to 12 hr. These results were compared with those obtained with two glucose-linked chloroethylnitrosoureas, chlorozotocin and 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea. Both of these agents have low marrow toxicity at therapeutic doses. Chlorozotocin, which has very low chemical carbamoylating activity, was found to permit approximately 40% removal of drug-derived DNA adducts in both systems within the first 6 hr and approximately 50% by 18 hr. The second glucose-linked analog, 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea, has relatively high carbamoylating activity and was found to inhibit early removal of DNA adducts as effectively as does 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. It would thus appear that the selective marrow-sparing property of the sugar-linked chloroethylnitrosoureas is not dependent upon carbamoylation-mediated differences in the rate and extent of DNA adduct removal. In view of the comparable therapeutic activity of the three drugs for L1210 leukemia, therapeutic efficacy does not appear to be impaired by the increased rate of adduct removal observed with chlorozotocin in this system.

Alkylation↗
PubMed1979

Myopathy of chronic organophosphate poisoning: a clinical entity?

The acute aspects of organophosphate poisoning are well understood. Persistent weakness and muscular wasting in some cases have been attributed to neuropathic effects resulting in muscular atrophy from denervation. Recently, necrosis of skeletal muscle has been induced by chronic inhibition of cholinesterase with organic phosphates in a reproducible experimental model. The literature on organophosphate poisoning in man alludes to cases in which it appears plausible to postulate this mechanism as a cause of a residual myopathy. A new case in which chronic organophosphate intoxication may be implicated in the etiology of a proximal myopathy is presented. Reports of additional cases, followed up from the onset of symptoms, are needed to determine whether primary myopathic effects are a clinically significant complication of chronic organophosphate poisoning.

Adult↗
PubMedDate not supplied

Dynamic CT vs 0.5 T MR imaging in the detection of surgically proven hepatic metastases.

Seventeen patients with 52 surgically proven hepatic metastases were studied preoperatively with dynamic CT and 0.5 T magnetic resonance (MR). Dynamic CT detected 38 metastases (73%), and the combination of short echo time (T1-weighted) and T2-weighted pulse sequences detected 46 lesions (88%). Magnetic resonance was also superior at assessing potential resectability. This study suggests that MR excels in detecting and anatomically localizing individual hepatic metastases.

Humans↗
PubMedDate not supplied

Phase II trial of lymphoblastoid interferon in metastatic malignant melanoma.

Thirty-three patients with metastatic malignant melanoma, some of whom had received previous chemotherapy, immunotherapy, or radiotherapy, were entered in a trial of three different doses and schedules of administration of lymphoblastoid alpha interferon. The overall response rate was 9%; some patients had long-lasting response and two achieved complete response. There was no clear advantage to any one regimen. Dose-related flu-like syndrome, granulocytopenia, hepatocellular enzyme elevation, and anemia were observed as the most common toxic effects. Interferon deserves further study in the treatment of malignant melanoma.

Adult↗
PubMedDate not supplied

Pulmonary disease as a complication of chlorozotocin chemotherapy.

Two of 200 patients treated with chlorozotocin have evidenced interstitial pulmonary disease. The cumulative doses of chlorozotocin were 480 and 670 mg/m2 when symptoms developed. Pulmonary function tests in both patients showed impaired diffusion, and an alveolar-arterial gradient which worsened with exercise. Open-lung biopsy in one patient showed typical interstitial inflammation and early fibrosis, and excluded lymphangitic spread of tumor. Discontinuation of chlorozotocin resulted in either improvement or stabilization of the pulmonary disease.

Adult↗