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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
PubMed1997

Treatment of advanced pancreatic carcinoma with a combination of protracted infusional 5-fluorouracil and weekly carboplatin: a Mid-Atlantic Oncology Program Study.

BACKGROUND: Advanced pancreatic cancer is a rapidly fatal disease whose course has been little influenced by chemotherapy. Earlier studies have shown some modest promise for the combination of protracted infusional 5-fluorouracil (PIF) and cisplatin. We sought to evaluate a regimen of possibly lesser toxicity, PIF plus weekly carboplatin. PATIENTS AND METHODS: Fifty-four patients with advanced adenocarcinoma of the pancreas were treated with a regimen of protracted infusional fluorouracil 300 mg/m2/day for 70 days and carboplatin 100 mg/m2/weekly on weeks 1 through 10 of a 12-week cycle. After a two-week rest, cycles were repeated until progression. RESULTS: Median duration on treatment was 82 days (range 4-490 days). Toxicity was mild. Grade 3-4 toxicities were anemia 11%, leukopenia 6%, thrombocytopenia 2%, nausea/ vomiting 7%, diarrhea 9%, mucositis 9%, and renal 2%. Response was evaluable in 47 patients. There were two complete and seven partial responses (17% overall objective response rate among all patients). Stable disease for greater than 12 weeks was seen in 19 patients (40%) and progression in 19 (40%). The median overall survival was 22 weeks (1-99), with 61 weeks median survival in responders (22-99). One-year survival was 13%. CONCLUSIONS: Response and survival results with this regimen are at least equal to the best combination regimens reported, and were obtained with a low overall rate of serious toxicity.

Adult↗
PubMed1996

Chemotherapy for pancreatic carcinoma.

BACKGROUND: Pancreatic cancer is an aggressive disease and its patients typically have a short survival, usually marked by pain and rapid debilitation. The disease has been considered relatively chemoresistant, although many chemotherapy regimens have been described. METHODS: Clinical results with chemotherapy, since the first publication of response in 1960, were reviewed for efficacy and toxicity. Emphasis was given to prospective trials with adequate power and clear evaluation criteria and endpoints. RESULTS: Published response rates vary enormously in this disease, with rates in earlier single-institution trials tending to be much higher than those in studies with stringent response criteria, particularly recent cooperative group trials. Using stringent criteria, the upper limit of the objective response rate is approximately 20%. No convincing improvements in median survival can yet be attributed to chemotherapy. Few trials have measured quality of life, but symptomatic palliation rates may exceed objective response rates. Some low-toxicity regimens (such as those based on infusional 5-FU) yield response rates as high as some more toxic combinations. CONCLUSIONS: Many early trials significantly overstate the efficacy of chemotherapy for patients with pancreatic cancer, apparently due to flexibility of response criteria. However, useful symptomatic palliation may occur even without an objective partial response. It is possible that slow resolution of the desmoplastic component of these tumors may underestimate tumor killing. Thus, quality of life is an important parallel endpoint (with survival and response) in chemotherapy trials in this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Epidemiology and risk factors in pancreatic cancer.

Pancreatic cancer is one of the most lethal neoplasms. Incidence in the United States has remained fairly stable over the past 25 years, with about 25,000 cases annually. Almost 100% of cases are fatal. Incidence in the developed world parallels that in the United States. Incidence in undeveloped nations is lower but may be underreported. Worldwide incidence is about 185,000 cases per year. There are no striking environmental risk factors, and geographic variation is less than with other gastrointestinal cancers. The most significant risk appears to be cigarette smoking, with a risk ratio of about 2. Alcohol and coffee consumption have been reported as possible risks in some (but not in most) studies. Diet is probably a significant factor, but is difficult to evaluate quantitatively. Other putative associations, including diabetes, probably are unimportant.

Alcohol Drinking↗
PubMed1993

Recent advances in the treatment of advanced colorectal cancer.

The treatment of advanced colorectal cancer has improved in recent years. Prospective randomized trials comparing innovative therapies with the "standard" bolus dose of 5-fluorouracil (5-FU) found increased response rates after biochemical modification of the drug, infusion administration of 5-FU, and direct intrahepatic arterial infusion. Although the impact on survival of these techniques has been minimal, it is possible that these innovative approaches provide an incremental survival advantage for certain subgroups of patients that may be the foundation for additional therapeutic improvements in the future.

Antineoplastic Combined Chemotherapy Protocols↗
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↗