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Biomedical subjects

J L Berenberg

Publications and source records attributed to J L Berenberg.

At least 19 recordsLinked to original sources

Phase II study of 5-fluorouracil and folinic acid in the treatment of patients with advanced gastric cancer. A Southwest Oncology Group study.

BACKGROUND: The biochemical modulation of 5-fluorouracil (5-FU) by the reduced folate folinic acid (FA) in the treatment of patients with advanced gastric cancer was examined. METHODS: The Southwest Oncology Group performed parallel randomized Phase II trials of two schedules of 5-FU and FA in 80 patients with advanced gastric cancer. Of 76 analyzable patients, 36 were randomized to receive bolus FA (200 mg/m2, days 1-4) along with continuous infusion 5-FU (1000 mg/m2, days 1-4) and 40 were randomized to receive bolus FA (200 mg/m2, days 1-5) before the bolus 5-FU (375 mg/m2, days 1-5). RESULTS: There were three (8%) partial responses (95% confidence interval [CI] 2%-22%) on the continuous infusion arm. The bolus arm had two (5%) complete responses and six (15%) partial responses for an overall response rate of 20% (95% CI 9%-36%). The median duration of response was 4.6 months for the infusion patients and 16.6 months for the bolus patients. Survival was poor, with median survival of 5 months on both regimens. Gastrointestinal toxicity was substantial, with Grade 3 mucositis observed in 36% of patients on the continuous infusion regimen versus only 10% of patients on the bolus regimen. Grade 3 or higher hematologic toxicity occurred more often in the bolus arm than in the continuous infusion arm (28% vs. 14%, respectively). Two toxic deaths occurred, one related to sepsis the other secondary to coronary insufficiency. CONCLUSIONS: Biochemical modulation of 5-FU by FA using the dose and schedules tested has only modest activity in the treatment of advanced gastric cancer.

Adenocarcinoma↗

Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A Southwest Oncology Group study.

PURPOSE: To evaluate FAM [5-FU (5-fluorouracil), doxorubicin, mitomycin C] chemotherapy as adjuvant therapy for patients with resected TNM stage I, II, or III gastric carcinoma. PATIENTS AND METHODS: One hundred ninety-three eligible patients were accrued from 1978 to 1991 in a phase III trial comparing six cycles (1 year) of postoperative FAM chemotherapy with observation only. RESULTS: The median follow-up on this study was 9.5 years. For all patients, no differences (log-rank analysis) in disease-free survival (p = 0.45) and overall survival (p = 0.57) between FAM therapy (93 cases) and surgery (100 cases) were observed. Quality of surgical resection affected survival irrespective of FAM use. Cases with curative resection, defined in a retrospective review of pathology and surgical reports as cases having no evidence of residual disease in the abdomen and tumor-free margins > 1 cm, had superior survival compared to cases not meeting these requirements (p < 0.001). FAM was well tolerated with 6% (five of 90) of cases demonstrating grade IV hematologic toxicity. There were two drug-related fatalities (one cardiomyopathy, one hematolytic uremic syndrome). CONCLUSION: FAM is not effective adjuvant therapy for TNM stage I, II, and III patients with resected gastric cancer. Future adjuvant studies must emphasize prospective surgical quality control to assure enrollment of appropriately staged and resected cases and wide participation to assure adequate case accrual over a reasonable period.

Adenocarcinoma↗

Treatment of advanced colorectal carcinoma with 5-fluorouracil, leucovorin and Roferon-A: a Southwest Oncology Study Group Study.

Based upon prior data suggesting that alpha-interferon possesses chemomodulatory activity, a pilot study was conducted in which patients with advanced colorectal carcinoma were treated with 5-fluorouracil (5-FU), leucovorin (LV) and Roferon-A. Treatment consisted of LV 20 mg/m2 i.v. push followed by 5-FU, 425 mg/m2 i.v. push daily for 5 days every 4 weeks for 2 cycles, then every 5 weeks; Roferon-A 9 million units subcutaneously was given three times weekly every week. Forty-six eligible patients with bidimensionally measurable disease who had received no prior chemotherapy for advanced disease were treated with this regimen. The most frequent toxicity was leukopenia with 80% of patients experiencing some degree of leukopenia and the most severe toxicity was granulocytopenia with 46% of patients experiencing granulocyte counts < 1,000/mm3. Among the 46 eligible patients, the objective response rate was 13% (95% confidence interval, 5-26%). Thirty-five of the 46 patients have died with a median survival of 17 months. This regimen has significant toxicity and insufficient activity against advanced colorectal carcinoma to warrant further trials.

Adult↗

VM-26 in gastric cancer. A Southwest Oncology Group study.

The Southwest Oncology Group conducted a trial of VM-26 (teniposide) in patients with advanced gastric cancer. VM-26 60 mg/m2 i.v. infusion over 30-45 minutes was given daily for 5 days every 21 days. Twenty-one eligible patients with measurable disease and a SWOG performance status of 0-2 were analyzed for response and toxicity. Partial responses were seen in 2 of the 21 eligible patients (9.5%). Median survival was 3.8 months. Severe of life-threatening toxicity was observed in 13/21 (62%) patients. This included two drug related deaths related to neutropenic sepsis and seven other patients with grade 4 granulocytopenia (< 500/mm3). Liver dysfunction and hypotension were seen less often and were not dose limiting. Although the modest activity seen was comparable to that of VP-16 (etoposide) as a single agent, the hematologic toxicity observed in this trial would likely preclude further trials of VM-26 (teniposide) in advanced gastric cancer.

Adult↗

A phase II evaluation of ifosfamide and mesna in unresectable diffuse malignant mesothelioma. A Southwest Oncology Group study.

BACKGROUND: Malignant mesothelioma is a highly treatment-resistant neoplasm. This study represents an attempt to define an effective form of systemic therapy. METHODS: Twenty-six patients with unresectable diffuse malignant mesothelioma were enrolled in Southwest Oncology Group (SWOG) study 8731 and treated with ifosfamide, 2 g/m2 intravenously for 4 days, and mesna 2 g/m2 intravenously for 5 days, every 3 weeks. Patients were either previously untreated with chemotherapy or had at most one prior systemic treatment. RESULTS: Two patients, or 8% (95% confidence interval, 1-25%), achieved partial response, with response durations of 4 and 6 months. One additional patient met criteria for tumor size reduction but not duration criteria. Thirteen (50%) patients had stable disease of 4 months' median duration (range, 1-13 months). The median survival of the entire group was 6.5 months. The dose-limiting toxicity was granulocytopenia (11 patients, < or = 250/microliters). CONCLUSIONS: Ifosfamide/mesna has modest activity in malignant mesothelioma. It could be tested using alternate dosage schedules and in combination with other agents in treating this highly resistant neoplasm.

Adult↗

Response to treatment of breast cancer.

Variability in outcome of breast carcinoma among different racial groups has been identified between Japanese and Caucasians and between Caucasians and Blacks living in the United States. These differences are not fully explained by population differences of the known prognostic variables nodal involvement and tumor hormonal receptor status. Further elucidation of the differences in outcome should include a careful examination of other prognostic variables. These include tumor size, nuclear and histologic grade, and indicators of cell proliferation (labelling index and flow cytometric measures of S phase and DNA ploidy). More recent studies indicate that growth factor regulation, oncogene amplification (HER-2/neu) and expression, and cathepsin D levels may help to further identify prognostic subgroups. A review of the literature does not provide an answer to the question of whether there are population differences in response to standard treatments. Differences in drug distribution, elimination, and metabolism which could be related to genetic or dietary factors are intriguing hypotheses to explain why differences may exist. Careful, well controlled studies to answer these questions are urgently needed.

Asian People↗

Microangiopathic hemolytic anemia as the initial manifestation of porcine valve failure.

We compare the findings in a patient whose microangiopathic hemolytic anemia was the initial sign of porcine valvular dysfunction, with those of six other patients with porcine valve failure seen at Tripler Army Medical Center and with those of 12 patients with hemolytic anemia and porcine valve failure whose cases have been reported in the literature. Total bilirubin and serum lactic dehydrogenase were directly related to the degree of anemia in patients with porcine valve dysfunction. Echocardiography confirmed valve dysfunction in only four of eight patients, while cardiac catheterization confirmed valve failure in 16 of 17 patients. Laboratory evidence for hemolysis was minimal in 31 patients who had normal, functioning porcine valves. Microangiopathic hemolytic anemia in the presence of a porcine prosthetic heart valve, and in the absence of other causes, warrants a thorough evaluation to rule out valve dysfunction. Routine laboratory screening for hemolysis may aid the early diagnosis of porcine valve failure.

Anemia, Hemolytic↗

Disseminated coagulopathies and advanced malignancies.

Among patients with various malignancies, three to 15 per cent may have associated idiopathic thrombosis. In a two-year period, we saw three patients with signs and symptoms demonstrating the association of neoplasia and coagulopathy. Their clinical courses and eventual outcomes are summarized. All had thrombophlebitis of multiple sites. There were difficulties in demonstrating their underlying occult malignancies, and all three patients showed resistance to oral anticoagulation drugs. Current hypotheses concerning the pathophysiology of coagulopathy associated with cancer are discussed, and recommendations for management of such patients were presented.

Adenocarcinoma↗

Primary liver cancer in a referral hospital in Hawaii.

This is a retrospective review of 43 patients who had primary liver cancer diagnosed during 1974-1983. Patients' ages ranged from 27 to 84 years (median 52.5). Nine of 39 patients with hepatoma were females, while two of the four patients with cholangiocarcinoma were women. Hepatitis surface antigen was positive in 90% tested, and 62% had cirrhosis. Also, 60-65% were heavy users of alcohol and cigarettes. Alpha-fetoprotein was elevated in one of four white patients, and in six of eight patients of other races (75%). Tissue diagnosis was obtained by peritoneoscopy in 16, by percutaneous biopsy in 7, by laparotomy in 9, and at autopsy in 11. Only one of 11 patients who were explored has his lesion resected. About half of the cases diagnosed antemortem died 1 month or less after diagnosis. The median survival of hepatoma patients who had no specific treatment or systemic chemotherapy was 2 months. Two patients who received chemotherapy in conjunction with occlusion of the hepatic artery lived 16 to 19 months.

Adult↗

Therapy of refractory adult acute lymphoblastic leukemia with vincristine and prednisone plus tandem methotrexate and L-asparaginase. Results of a Cancer and Leukemia Group B Study.

Methotrexate (MTX) and L-asparaginase (ASP) are effective agents in the treatment of acute lymphoblastic leukemia (ALL). The effects of combining MTX and ASP are schedule dependent. To investigate this schedule dependency, the Cancer and Leukemia Group B (CALGB) employed vincristine and prednisone with progressive dose escalation of moderate-dose MTX (125 mg/m2) followed 24 h later with ASP (6,000 U/m2) in refractory adult ALL. We treated 38 patients with refractory or first relapse adult ALL. Most patients had received prior ASP (92%) and MTX (72%). A complete remission was achieved in 25% with a median duration of remission of 21 weeks. The median survival for the entire group was 7.4 months. Therapy was well tolerated and toxicity was acceptable. Our response rate was lower than other tandem MTX and ASP adult ALL trials. Therapy was similar with other series, with the exception of the dose of ASP employed. We conclude that tandem MTX and ASP, in the doses and schedule used here, has only modest activity in previously treated adult ALL. This regimen offers little advantage to other salvage regimens.

Adult↗

Hereditary warfarin resistance. Investigation of a rare phenomenon.

A 57-year-old black woman required a daily dosage of 50 mg of warfarin sodium to maintain her prothrombin time in a therapeutic range. The central volume of distribution and clearance of warfarin were normal for this patient. These findings, combined with the patient's requirement for plasma warfarin levels four times greater than those usually required to achieve adequate anticoagulation, indicated that the relative resistance was due to altered pharmacodynamics of warfarin. The only child of the propositus, a daughter, showed a similar relative resistance, confirming that this family is the third to be reported with hereditary resistance to warfarin.

Adult↗

Vinblastine, bleomycin and cisplatin for recurrent or metastatic squamous cell carcinoma of the head and neck.

Forty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with vinblastine, bleomycin, and cisplatin. All patients had received prior surgery, radiation or chemotherapy and all had measurable disease. Forty-five percent of the patients responded with a median duration of response of eight months and median survival of nine months. Six patients (14%) were complete responders and had a median duration of response of 12 months and median survival of 24+ months. Thirteen patients (31%) were partial responders and had a median duration of response of seven months and survival of 13 months. Toxicity was mild with nausea and vomiting occurring in all patients after cisplatin. There were two cases of bleomycin-induced pulmonary fibrosis and two cases of mild renal insufficiency (creatinine clearance level, 45 cc/min). This regimen compares favorably with other published regimens for advanced head and neck cancer.

Bleomycin↗

Bone marrow phagocytosis in sarcoidosis.

The phagocytic activity of the bone marrow monocytes and macrophages was studied in 22 patients with sarcoidosis, 28 patients with Hodgkin's and non-Hodgkin's malignant neoplasms, and 14 controls. Although phagocytosis of RBCs and WBCs and platelets were seen in all bone marrow specimens, the activity was considerably increased in some patients with stage I and stage II sarcoidosis. This observation may reflect the presence of an unusual host response to unknown antigens in patients with sarcoidosis.

Adult↗

Treatment experience with nonseminomatous testicular cancer in patients with stage II and stage III disease.

Thirty-eight patients with nonseminomatous testicular cancer were treated with cis-platinum, bleomycin, and vinblastine in combination without a prolonged maintenance phase. Twenty-Six patients with Stage III disease were treated. Seventy-six percent of those patients treated achieved complete remission. At a median survival time of 30 months, no patient who achieved a complete remission has relapsed. Twelve Stage II patients given adjuvant therapy remain free of disease at a median time of 23 months. Markedly elevated serum lactate dehydrogenase levels and massive disease were common findings in the patients who did not achieve complete remission. One drug death occurred secondary to sepsis. Symptoms of depression and anxiety were significant dose-limiting factors in this group of patients.

Adolescent↗

Chemotactic factor inactivator in normal human serum.

Normal human serum contains an inactivator of chemotactic factors for neutrophilic leukocytes. The chemotactic factor inactivator (CF-I) remains soluble when serum is fractionated with ammonium sulfate (at 45% saturation), directly and irreversibly inactivates chemotactic factors, and it has a broad spectrum of activity as indicated by its inactivation of the chemotactic fragments of human C3 and C5 (third and fifth components of complement), C567, and the bacterial chemotactic factor derived from Escherichia coli. CF-I appears as a biphasic activity according to preparative techniques of sucrose density ultracentrifugation, electrophoresis, and gel filtration. Studies on the interaction of CF-I with the radiotagged C5 chemotactic fragment fail to reveal evidence for irreversible binding as the basis for inactivation. CF-I varies from the anaphylatoxin inactivator in several physical-chemical respects, but evidence does not permit a conclusive statement about the relationship of the two inactivators. CF-I may function as a regulator of inflammatory responses.

Blood↗