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Biomedical subjects

J D Ahlgren

Publications and source records attributed to J D Ahlgren.

At least 19 recordsLinked to original sources
PubMed1993

Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid-Atlantic Oncology Program.

PURPOSE: To evaluate the efficacy of three hormonal manipulations in the palliation of chemoresistant ovarian cancer, and to analyze the results in the light of other clinical trials. PATIENTS AND METHODS: Three sequential phase II trials were performed in patients with refractory epithelial ovarian carcinoma, using high-dose megestrol acetate (800 mg/d for 30 days, then 400 mg/d), high-dose tamoxifen (80 mg/d for 30 days, then 40 mg/d), and aminoglutethimide (1 g/d plus tapering doses of hydrocortisone). Results were compared with those described in the world literature from trials of the same or similar agents. RESULTS: No responses were seen among 30 assessable patients treated with megestrol acetate, and most (but not all) similar trials have reported low response rates. Five responses (17%) were seen among 29 patients treated with tamoxifen. Two responses exceeded 5 years in duration. No responses were seen among 15 patients treated with aminoglutethimide. CONCLUSION: Antiestrogen therapy may offer the possibility of useful and, occasionally, long-term palliation of refractory epithelial ovarian carcinoma, with little toxicity. There may be a trend toward a dose-response effect, which represents a suitable topic for a future prospective trial.

Adenocarcinoma↗
PubMed1992

Gas chromatographic-mass spectrometric method for routine monitoring of 5-fluorouracil in plasma of patients receiving low-level protracted infusions.

A gas chromatographic-mass spectrometric (GC-MS) method is described which quantitates 5-fluorouracil (5-FU) plasma levels ranging from 0.5 to 50 ng/ml. The analysis uses two internal standards, 1,3-[15N2]-5-fluorouracil and 5-chlorouracil. Extraction and derivatization of the pyrimidine bases were accomplished in a single step using acetonitrile. Compounds were analyzed as their 1,3-dipentafluorobenzyl derivatives by electron-impact MS, and the GC-MS analysis was automated with respect to sample injection and data reduction. Stability of the analysis was demonstrated by continuous unattended analysis of 5-FU in human plasma for periods of up to three days with no deterioration of the quantitative results. The method is applicable to quantitating 5-FU plasma levels in patients receiving protracted infusions of the drug for colorectal cancer or other malignancies.

Drug Monitoring↗
PubMed1992

A study of oral etoposide, infusional cisplatin, and infusional 5-fluorouracil for locally advanced or metastatic non-small-cell lung cancer. A Mid-Atlantic Oncology Program study.

A combination of oral etoposide, infusional cisplatin (24-hr) and infusional 5-fluorouracil (5-day) was used to treat 87 patients with non-small-cell lung cancer in a Phase II trial. Twenty-six patients were Stage IIIB, and 61 patients were Stage IV (new international classification). The regimen was well tolerated, with 49% grade 3 or 4 toxicities of all types. Response rates, partial and complete, were 40%, (95% confidence interval: 30%, 51%) for Stage IV patients and 20% (95% confidence interval: 10%, 32%), in Stage IIIB. An additional 68% of patients in Stage IIIB and 45% of patients in Stage IV achieved stable disease and had a median survival of 8.8 months, similar to that of patients in partial remission. Median survival was 5.6 months (95% confidence interval: 4.4 months, 10.8 months) for Stage IV patients and 11.0 months (95% confidence interval: 8.8 months, 12.4 months), for Stage IIIB. Of interest was the finding of a higher response rate in patients with a shorter duration of symptoms (less than 6 months versus greater than 6 months).

Administration, Oral↗
PubMed1992

A pilot study of intensive weekly chemotherapy for extensive disease small-cell lung carcinoma.

An intensive weekly chemotherapeutic treatment for extensive disease small-cell lung cancer was piloted in 14 patients. The regimen consisted of 6 drugs. Two drugs were given each week for a total of 12 weeks of treatment. Modifications were required in the protocol to attempt to overcome excessive toxicity. Unexpected toxicity included anemia requiring transfusions in 8 of 10 patients completing treatment, sepsis in 8 of 14 with 3 related deaths, and prolonged grade III motor neurotoxicity in 2 patients. All 3 patients who died of sepsis had shown evidence of response, and 8 of the remaining 11 had 90% or greater tumor shrinkage. Two others had a partial response. Median survival time for all patients was 9.3 months.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A prospective randomized comparison of protracted infusional 5-fluorouracil with or without weekly bolus cisplatin in metastatic colorectal carcinoma. A Mid-Atlantic Oncology Program study.

One hundred eighty-four 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 assess the value of weekly cisplatin (20 mg/m2) when added to a protracted schedule of 5-fluorouracil (5-FU) infusion (PIF) at 300 mg/m2/d for 10 weeks of every 12 weeks. The liver was the primary indicator lesion in approximately 75% of the study group. All tumor measurements required radiographic confirmation. The response rate in the PIF alone arm was 35% (29 of 83; 95% confidence interval [CI], 25% to 46%) compared with 33% (28 of 85; 95% CI, 23% to 44%) for the arm in which weekly cisplatin was added to PIF. The median survival times were 11.8 and 11.2 months in the two groups. Weekly cisplatin does not appear to add to the effectiveness of PIF in colorectal carcinoma.

Aged↗
PubMed1991

Dichloromethotrexate, infusional cisplatin, and infusional 5-fluorouracil for locally advanced or metastatic non-small cell lung cancer. A MAOP study.

The combination of dichloromethotrexate, cisplatin, and infusional 5-fluorouracil was evaluated as treatment for non-small-cell lung cancer in a phase II trial using 43 evaluable patients. Grade III or IV toxicity included thrombocytopenia (21%), leukopenia (14%), nausea/vomiting (14%), mucositis (9%), infection (5%), and other (16%). There were six responders (14%), with a 95% confidence interval of [5%, 28%]. Two additional patients achieved a 50% reduction in cross-sectional tumor size that was not documented twice. Median survival time was 6.5 months. This combination is not considered sufficiently active for further evaluation in this disease.

Adult↗
PubMed1991

A study of infusional cisplatin and infusional fluorouracil for locally advanced or metastatic non-small-cell lung cancer: a Mid-Atlantic Oncology Program study.

A combination of cisplatin administered as a 24-hour infusion and fluorouracil administered as a 5-day infusion was used to treat 97 patients with non-small-cell lung (NSCLC) cancer in a phase II trial. Thirty patients had stage IIIB disease; 67 patients, stage IV disease (new international classification). Patients with stage IIIB disease also received thoracic radiation after chemotherapy. The regimen was well tolerated, with 24% or less grade 3 or greater toxicities of all types. One toxic death was attributed to fluid overload. The response rate, partial and complete, was 43% (95% confidence interval, 27% to 63%), and median survival was 13.8 months for patients with stage IIIB disease. Response rates refer to the chemotherapy response. For patients with stage IV disease, the response rate was 34% (95% confidence interval, 24% to 47%), and median survival was 6.2 months. On this regimen, stable-disease patients with stage IV disease had survivals at least equal to responders.

Adult↗
PubMed1991

Comparison of cyclophosphamide, doxorubicin, and vincristine with an alternating regimen of methotrexate, etoposide, and cisplatin/cyclophosphamide, doxorubicin, and vincristine in the treatment of extensive-disease small-cell lung carcinoma: a Mid-Atlantic Oncology Program study.

An alternating regimen for the treatment of extensive-disease small-cell lung cancer (SCLC) was compared with standard treatment with cyclophosphamide, doxorubicin, and vincristine (CAV) in 170 patients. Overall severity of toxicity was similar in both arms, with four toxic deaths in each arm (4.7%). Response results were also similar, with 54% complete and partial responses with the standard regimen and 53% complete and partial responses with the alternating regimen. Median survival time was 6.9 months with the standard regimen and 9.2 months with the alternating regimen (P = .078). The 2-year survival rate was 1.2% for the standard regimen and 4.7% for the alternating regimen. Survival benefit for treatment with the alternating regimen reached statistical significance only in those subsets of patients with poorer prognosis (male sex, performance status 3, liver metastases, bone marrow metastases, and oat cell histologic subtype).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Protracted infusion of 5-FU with weekly low-dose cisplatin as second-line therapy in patients with metastatic colorectal cancer who have failed 5-FU monotherapy.

Forty four patients who had documented progression of metastatic colorectal cancer while receiving 5-fluorouracil (5-FU) monotherapy were treated with continuous infusion 5-FU, 300 mg/mg2/day, plus weekly low-dose cisplatin, 20 mg/m2. Treatment was given in 12-week cycles, consisting of 8 weeks of chemotherapy followed by a 4-week rest period, and was well tolerated. Three of 23 patients (13%) who had failed bolus 5-FU but not been exposed previously to infusional 5-FU responded. Of 21 patients who had failed infusional 55-FU monotherapy, only one (5%) responded. Time to progression (5.7 vs. 1.8 months) and survival (12 vs. 5.5 months) were significantly longer for patients who had not previously received infusional 5-FU but who had failed bolus schedules, compared with patients who had previously failed infusional 5-FU (p less than .001).

Adult↗
PubMed1989

Therapy of advanced gastric carcinoma. The Georgetown-Lombardi Cancer Center experience.

Gastric carcinoma, despite a decreasing incidence in the United States over the past 40 years, is the seventh most common cause of cancer death in this country and remains a significant worldwide problem. The 5-fluorouracil, Adriamycin (doxorubicin), and mitomycin (FAM) chemotherapy regimen, which was initially reported by Georgetown in 1979, has become a standard for advanced gastric carcinoma with response rates in the 40% range. The FAM regimen as well as subsequent trials conducted at Georgetown and our current approach to management of this tumor are discussed. Despite a decade of intensive clinical research, we have not identified a modification or innovation that is superior to the original FAM.

Adult↗
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↗