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Biomedical subjects

D G Haller

Publications and source records attributed to D G Haller.

At least 73 records · Page 4Linked to original sources
PubMed1993

An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer.

OBJECTIVE: To determine the effectiveness of carcinoembryonic antigen (CEA) monitoring in detecting surgically curable recurrence of colon cancer. DESIGN: Clinical data were collected from a national surgical adjuvant trial in which CEA monitoring was elective. SETTING: Cancer centers, universities, and community clinics. PATIENTS: A total of 1216 patients with resected colon cancer, 1017 (84%) of whom had CEA monitoring. MAIN OUTCOME MEASURES: Sensitivity and specificity of CEA testing for cancer recurrence and CEA-motivated diagnostic and surgical interventions and their end results. RESULTS: Among 417 monitored patients with recurrence, 59% had a preceding elevation of CEA concentration. Sixteen percent of 600 patients without recurrence showed a false-positive test result. Carcinoembryonic antigen testing was most sensitive for hepatic or retroperitoneal metastasis and relatively insensitive for local, pulmonary, or peritoneal involvement. Surgical explorations were performed in 115 patients with CEA elevations, and 47 recurrences, usually hepatic, were resected with curative intent. On the other hand, 38 patients with normal CEA concentrations and 23 patients not monitored also underwent such resections--usually for pulmonary or local recurrence. Of all CEA-monitored patients, 2.3% are alive and disease free more than 1 year after salvage surgery (2.9% of those with CEA elevations and 1.9% of those with no elevations). Of patients with no CEA monitoring, 2.0% are also alive and disease free more than 1 year after salvage surgery. CONCLUSIONS: Cancer cures attributable to CEA monitoring are, at best, infrequent. It is questionable whether this small gain justifies the substantial cost in dollars and physical and emotional stress that this intervention may cause for patients.

Biomarkers, Tumor↗
PubMed1993

Nonsurgical management of recurrent colorectal cancer.

Most patients with colorectal carcinoma undergo attempts at curative surgery. However, some present with metastatic disease and many others ultimately relapse. Most recurrences of colorectal cancer are not resectable and require nonsurgical approaches such as chemotherapy and radiation therapy directed against local recurrences, hepatic metastases, and widely disseminated disease. Nonsurgical therapy for locoregional recurrence of rectal cancer can offer significant palliation. Intraarterial chemotherapy for liver metastases increases the likelihood of response compared to systemic treatments, but has little effect on survival. Extrahepatic progression and hepatic toxicity are important limitations to this regional therapy. 5-fluorouracil (5-FU) is the mainstay of systemic chemotherapy, and efforts to modulate biochemically the cytotoxic effects of 5-FU with folinic acid, phosphonacetyl-L-aspartate, interferon, and other agents have resulted in promising response rates. The different approaches to biochemical modulation are being studied in ongoing cooperative group trials. Novel approaches, including monoclonal antibody therapy, biologic modifier therapy, and gene therapy, are under investigation.

Colonic Neoplasms↗
PubMed1993

Phase II multicenter evaluation of prolonged murine monoclonal antibody 17-1A therapy in pancreatic carcinoma.

Twenty-eight patients with unresectable, measurable pancreatic carcinoma and Eastern Oncology Cooperative Group (ECOG) performance status of 0 or 1 were treated with the murine monoclonal antibody 17-1A, planning to administer 500 mg i.v. three times weekly for 8 weeks. Treatment was well tolerated, with an 18% incidence (five patients) of hypersensitivity reactions. All hypersensitivity episodes occurred in the first 3 weeks of therapy and required treatment discontinuation. Six patients required early discontinuation of therapy due to symptomatic progressive disease and one patient was removed from the study due to a protocol violation. Sixteen patients received the full course of 12 g of antibody. One patient has exhibited a durable partial response. Antibody pharmacokinetics were determined in five patients. In four patients peak 17-1A levels averaged 100 micrograms/ml with mean harmonic t1/2 of 16.8 h in a one-compartment model. Neither pretreatment nor posttreatment levels of circulating 17-1A changed significantly during the 8 weeks of treatment. This study demonstrates the feasibility and acceptable toxicity of repetitive dosing with an unconjugated murine monoclonal antibody. The lack of efficacy of treatment suggests that factors other than prolonged exposure of tumor and cytotoxic effector cells to murine antibody are required for successful antibody therapy of pancreatic cancer.

Aged↗
PubMed1993

Hepatic toxicity associated with fluorouracil plus levamisole adjuvant therapy.

PURPOSE: To determine the frequency and nature of hepatic toxicity associated with fluorouracil (5-FU) plus levamisole adjuvant therapy. PATIENTS AND METHODS: All patients had resection of stage II or stage III colon cancer and were randomized to receive observation only, levamisole alone, or 5-FU plus levamisole. Serial liver function studies were documented in 1,025 patients who did not develop recurrence during the year of therapy. RESULTS: One hundred forty-nine (39.6%) of 376 patients treated with 5-FU plus levamisole showed laboratory abnormalities consistent with hepatic toxicity, compared with 16.3% of 251 patients treated with levamisole alone and 16.1% of 398 untreated controls. Most common was elevation of alkaline phosphatase, frequently accompanied by elevations of transaminase or serum bilirubin. Characteristically, these changes were mild, not associated with symptoms, and resolved when therapy was stopped. In some instances, they were associated with elevated carcinoembryonic antigen (CEA) tests or with fatty liver seen on computed tomographic (CT) scan or liver biopsy. CONCLUSION: Mild and reversible hepatotoxicity is a common consequence of 5-FU plus levamisole adjuvant therapy, but this is only rarely symptomatic. However, the oncologist should be alert to this phenomenon, since the associated laboratory and imaging findings may simulate those associated with hepatic metastasis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Use of radiolabelled monoclonal antibodies in patients with primary and metastatic large bowel cancer.

Accurate assessment of the extent of primary and metastatic large bowel cancer is critical to surgical decision making and to providing reliable prognostic information. This prospective study compared external gamma camera images and an intraoperative hand-held gamma detecting probe for detection of radiolabelled monoclonal antibody (B72.3) in 28 patients with primary and metastatic large bowel cancer. Fourteen patients received 0.2 to 20 mg (2 or 5 mCi) 111indium-labelled monoclonal antibody B72.3 followed by whole body imaging scan with an external gamma detector/camera on two occasions 24 h apart within 7 days after injection. Fourteen patients received 1.0 mg (2.0 mCi) 125iodine-B72.3 followed by intraoperative probe evaluation 2-3 weeks postinjection. Mean patient ages for the two groups were 60 years (range 28-75 years) and 63 years (range 43-77 years), respectively. Disease sites were primary in the large bowel in six patients and primary as well as metastatic in 22 patients. External scanning detected 111indium-B72.3 uptake in 1/5 primary lesions, 1/7 hepatic and 1/3 extrahepatic sites. The intraoperative gamma probe localized disease in 1/3 primary lesions, 7/11 hepatic and 3/3 extrahepatic sites. The intraoperative gamma probe had a sensitivity of 71% for detection of metastases compared with a 20% sensitivity using the external gamma scan method (P = 0.03). 125iodine-labelled B72.3 influenced the extent of the operative procedure in 4/14 (29%) patients; immunolocalization with external gamma detection did not alter the operative procedure in the 14 patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

Phase II trial for the evaluation of trimetrexate in patients with inoperable squamous carcinoma of the esophagus.

EST 2287 was a Phase II clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) designed to evaluate trimetrexate in patients with advanced, measurable, inoperable squamous cell carcinoma of the esophagus. The drug was given at a dose of 12 mg/m2 daily for 5 days every 21 days to patients with carcinoma of the esophagus. The purpose of this study was to evaluate treatment efficacy in terms of tumor response and to assess the toxicity. According to a two-stage stopping rule, the study closed after 15 patients had entered. There were no responses to treatment, and median survival from study entry was 4.3 months. There was one treatment-related death caused by infection. One patient experienced life-threatening hematologic toxicity. Overall severe or worse toxicity occurred in more than half of the patients. It is concluded that additional trials of trimetrexate at this dose and schedule in patients with carcinoma of the esophagus are not warranted.

Aged↗
PubMed1992

Primary intestinal lymphoma in Crohn's disease: minute tumor with a fatal outcome.

A 54-yr-old man with a 22-yr history of Crohn's disease was found to have a microscopic focus of immunoblastic lymphoma within a segment of small bowel resected to relieve intestinal obstruction. There was no other clinically evident disease. Thirty months later, he developed axillary adenopathy with recurrent lymphoma of the same immunophenotype (IgA lambda) and was given combination chemotherapy, with complete clinical response. Lymphoma recurred 6 months later in the axilla and progressed rapidly over the next 3 months, despite chemotherapy. He developed extensive mediastinal, mesenteric, and retroperitoneal disease with malignant ascites and died 39 months after diagnosis of the incidentally discovered bowel mucosal primary tumor.

Axilla↗
PubMed1991

Adjuvant therapy of resected adenocarcinoma of the pancreas.

Seventy-two patients underwent resections of pancreatic carcinomas between 1981 and 1989 at the Hospital of the University of Pennsylvania and were evaluable for follow-up. There were three treatment groups as treatment policies evolved. Initially, patients were observed after surgery without adjuvant treatment (Group 1-33 patients). Beginning in 1984, patients were offered adjuvant radiation therapy postoperatively (Group 2-19 patients) and eight of these patients also received 5-FU as an IV bolus on the first 3 days of the first and fifth weeks of treatment. Twenty patients were treated with chemosensitized radiation therapy following surgery using 96-hour 5-FU infusions during the first and fifth weeks of treatment. There were four postoperative deaths, which are excluded from the analysis, and sites of failure could not be determined for five other patients. Among evaluable patients, local recurrences occurred in 85% of the patients in group 1, 55% of the patients in group 2, and 25% of the patients in group 3. The 2-year survival was 35% in group 1, 30% in group 2, and 43% in group 3. Patients with involved surgical margins had a poor survival; only 2 of these 16 patients survived longer than 18 months. Among patients with negative margins, the 2-year survival is 41% in group 1, 33% in group 2, and 59% in group 3. Although the number of patients is smaller, the 3-year survival is 22% in group 1, 11% in group 2, and 47% in group 3. Chemosensitized irradiation is well tolerated in these patients. The major challenge in this group of patients is nutritional maintenance. There was no other significant toxicity. The trend in these observations suggests that survival following pancreatic resection is substantially improved with the addition of adjuvant chemosensitized radiation therapy.

Adenocarcinoma↗
PubMed1991

Phase II study of aminothiadiazole in advanced squamous cell carcinoma of the esophagus.

Twenty-three patients with advanced inoperable squamous cell carcinoma of the esophagus were treated with aminothiadiazole (A-TD) 125 mg/m2 weekly plus allopurinol daily in a phase II cooperative group trial. No patients responded to treatment; 17 patients progressed, three showed stable disease, and three were unevaluable. There were no life-threatening hematologic or metabolic toxicities. The median survival from study entry was 5 months. A-TD is not active in advanced squamous cell carcinoma of the esophagus.

Adult↗
PubMed1990

Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma.

Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B2) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2). Among the patients with Stage C disease, therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent (P less than 0.0001). The overall death rate was reduced by 33 percent (P approximately 0.006). Treatment with levamisole alone had no detectable effect. The results in the patients with Stage B2 disease were equivocal and too preliminary to allow firm conclusions. Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone--i.e., nausea, vomiting, stomatitis, diarrhea, dermatitis, and leukopenia. These reactions were usually not severe and did not greatly impede patients' compliance with their regimen. We conclude that adjuvant therapy with levamisole and fluorouracil should be standard treatment for Stage C colon carcinoma. Since most patients in our study were treated by community oncologists, this approach should be readily adaptable to conventional medical practice.

Adolescent↗
PubMed1990

Adenocarcinoma of the esophagus and esophago-gastric junction: the effects of single and combined modalities on the survival and patterns of failure following treatment.

One hundred sixty-five patients with localized adenocarcinomas of the esophagus or esophago-gastric (EG) junction were treated with surgery alone, radiation therapy alone, chemotherapy alone, surgery followed by post-operative radiation therapy, chemotherapy, or chemosensitized radiation therapy, and chemosensitized radiation therapy alone. Patients were retrospectively evaluated for survival, control of tumor within the mediastinum, post-operative swallowing function, patterns of failure, and treatment-related morbidity. Follow-up of survivors ranges from 9-88 months (median 23 months). Chemotherapy and radiation therapy as single modalities were associated with a recurrence rate of 100%. Combined modality therapy significantly reduced the risk of local recurrence in all patient groups. Chemosensitized radiation therapy alone reduced the local recurrence rate to 48%, and surgery followed by radiation therapy reduced the local failure rate to 24%. When chemotherapy or chemosensitization was added to surgery plus radiation, the risk was further reduced to 15%. The use of combined modality therapy was also found to extend the survival of patients without excessive toxicity. Median survival was shortest among the group treated with radiation alone (5 months) and intermediate among patients following chemosensitized radiation alone (10 months) or complete surgical resection alone (15 months). Patients treated with all three modalities had the longest median survival (21 months). Based on this experience, the optimum treatment of these patients appears to include aggressive attempts at surgical resection with chemosensitized radiation therapy. Excellent palliation can also be achieved in unresectable patients with chemosensitized radiation therapy with a smaller chance for long term survival.

Adenocarcinoma↗
PubMed1990

A randomized phase II study of acivicin and 4'deoxydoxorubicin in patients with hepatocellular carcinoma in an Eastern Cooperative Oncology Group study.

We analyzed 56 of 75 previously untreated patients with hepatocellular carcinoma who entered on a prospectively randomized trial of acivicin versus 4'deoxydoxorubicin (esorubicin). At least one episode of severe toxicity was documented in 23% of the patients on acivicin and 45% of those on 4'deoxydoxorubicin. Two patients responded to 4'deoxydoxorubicin. One response was partial, lasting 58 weeks, and one was complete, lasting more than 4 years. The 90% confidence interval for response is 1-20%. In view of a 45% rate of severe or worse toxicity with 4'deoxydoxorubicin, this drug cannot be recommended as treatment. There were no responses on acivicin.

Antibiotics, Antineoplastic↗
PubMed1989

A phase II study of carboplatin and CHIP in patients with metastatic colon carcinoma.

Fifty-six patients were treated in each arm of a study comparing CHIP and carboplatin for the therapy of previously untreated metastatic colorectal carcinoma. There were one partial response (2%) with CHIP and two partial responses (4%) with carboplatin. Side effects were significantly more severe with CHIP than with carboplatin. The most common side effect for both drugs was vomiting followed by hematologic side effects. Sixteen percent of the patients receiving CHIP and 9% of those receiving carboplatin had life-threatening side effects. Neither drug offers significant activity in metastatic colorectal carcinoma.

Aged↗
PubMed1988

A phase II study of spirogermanium in advanced large bowel cancer. An Eastern Cooperative Oncology Group study.

Thirty-one patients with advanced colorectal cancer were entered on a phase II study of spirogermanium. Of these, 23 received the drug at the dose of 200 mg/m2 intravenously (i.v.) over 4 h twice a week every week. There were 2 (9%) partial responses. No complete responses were noted. Two life-threatening and six severe toxicities were observed. We conclude that this drug has some activity against colorectal cancer.

Aged↗
PubMed1988

Chemotherapy in gastrointestinal malignancies.

The frequency of gastrointestinal (GI) cancers mandates innovative and individualized therapies. Chemotherapy used as sole treatment for these diverse malignancies has not been generally successful in providing palliation or improving patient survival. Radiotherapy has been more successful at controlling local manifestations of disease, but the high incidence of systemic metastases in most malignancies limits the impact of this modality on curability. Combinations of radiotherapy and chemotherapy may prove to be more valuable than single modality treatment in improving local control of tumors, decreasing systemic disease, and improving patient tolerance to treatment. A model for this approach is the current management of anal cancer, in which combined modality therapy has largely supplanted primary surgery. Data from trials in other primary tumor sites strongly suggest further exploration of combined treatments--surgical, radiotherapeutic, and chemotherapeutic--in GI malignancies. Nearly 25% of all malignancies diagnosed in the United States each year involve the GI tract; thus, there is a powerful imperative for the development of new therapeutic strategies in these diseases. Any discussion of the role of chemotherapy in GI cancers must necessarily be broad, because assessment must include diseases with highly variable surgical curability, histologies, and sensitivities to chemotherapeutic agents. In addition, whereas it has been quite easy to perform standard phase II trials in colorectal cancer, other disease sites, such as the esophagus, the pancreas, and the biliary tract, have been much less extensively studied. In spite of these limitations, there is a wealth of data in the literature concerning the use of chemotherapy in GI malignancies. This article, while not exhaustive, describes the current status of chemotherapy for these diverse diseases, with emphasis on the role of mitomycin C.

Antineoplastic Combined Chemotherapy Protocols↗