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Biomedical subjects

A B Benson

Publications and source records attributed to A B Benson.

69 records · Page 4Linked to original sources
PubMed1989

Combination chemotherapy of advanced breast cancer. Comparison of dibromodulcitol, doxorubicin, vincristine, and fluoxymesterone to thiotepa, doxorubicin, vinblastine, and fluoxymesterone: an Eastern Cooperative Oncology Group Study.

Two Adriamycin (doxorubicin)-based chemotherapy regimens were investigated in patients with carcinoma of the breast who had failed prior systemic therapy. The two chemotherapy programs, dibromodulcitol, Adriamycin, vincristine, and Halotestin (fluoxymesterone) (DAVH), and thiotepa, Adriamycin, vinblastine, and Halotestin (TAVH), were chosen for comparison on the basis of reported response rates of 40% to 50% with remission durations of 11 months in patients refractory to other cytotoxic chemotherapy. Cycles of DAVH were repeated every 4 weeks. Cycles of TAVH were repeated every 3 weeks. Of 184 patients evaluable for response, 32% of patients treated with DAVH and 38% of patients treated with TAVH had a complete response (CR) or partial response (PR). An additional 5% of patients had nonmeasurable improvement in osseous disease for an overall rate of response (CR + PR + improvement) of 40%. Patients who had previously received cytotoxic chemotherapy for metastatic disease or had early failure after adjuvant therapy had a lower response rate to DAVH, but not to TAVH than those who did not fail prior chemotherapy. Duration of response and survival were similar with the two treatments. There were seven treatment-related deaths, five among patients receiving DAVH and two among patients receiving TAVH. Patients receiving DAVH had significantly more thrombocytopenia and neurologic toxicity than those receiving TAVH. These treatments appear to be reasonable second-line regimens and are good candidates to be used in initial therapy of metastatic disease or adjuvant therapy studies that explore the use of alternating non-cross-resistant combinations with cyclophosphamide, methotrexate, and 5-fluorouracil.

Adenocarcinoma↗
PubMed1989

Epithelioid hemangioendothelioma: cytomorphology and histological features of a case.

A case of epithelioid hemangioendothelioma involving the left lung, the 10th thoracic vertebra, and paravertebral soft tissues is presented. Preoperative sputum cytology was thought to show adenocarcinoma. Histologic examination demonstrated an intravascular bronchioloalveolar tumor; immunohistochemical staining for factor VIII-related antigen revealed strongly positive tumor cells. The cytomorphology of this rare neoplasm is discussed.

Aged↗
PubMed1989

Immunophenotypic analysis of colorectal carcinomas with monoclonal antibodies 47D10 and anti-carcinoembryonic antigen.

A series of 80 colorectal adenocarcinomas were analyzed immunohistochemically for the antigen recognized by a new monoclonal antibody (MCA) 47D10. These antigens are part of a complex family of substances similar to, yet distinct from carcinoembryonic antigen (CEA), and are termed nonspecific cross-reacting antigens (NCA). Formalin-fixed paraffin-embedded sections of colorectal adenocarcinomas were evaluated for the expression of these antigens and compared to the expression of CEA. Our study shows that 83.8% of the cases were positively stained for NCA while 91.3% were positive for CEA. Both antigens were coexpressed in 80% of the cases. No correlation was found between MCA 47D10 immunoreactivity and tumor grade, stage, size or location within the colon. In 25 cases, the benign colonic mucosa adjacent to the carcinoma stained positively with MCA 47D10. Normal colon does not express NCA as recognized by MCA 47D10, except in rare cells. Forty-eight of these cases had serum available for study. Both NCA and CEA were determined in these serum samples. Forty-two of these sera demonstrated elevated CEA levels, whereas only 8 showed increased levels of the 47D10 antigen(s). These findings suggest that the gene product(s) recognized by MCA 47D10 can be independently expressed or, more commonly, coexpressed with CEA in these tissues.

Adult↗
PubMed1987

Clodronate. A randomized study in the treatment of cancer-related hypercalcemia.

Malignancy-associated hypercalcemia is a common and recalcitrant problem. Current modes of therapy are often ineffective or prohibitively toxic. Clodronate disodium is a diphosphonate capable of inhibiting bone resorption resulting in a hypocalcemic effect. In this randomized, placebo-controlled study, we investigated the effect of hydration only (Rx-1) vs the effect of hydration plus either intravenously administered clodronate disodium, 4 mg/kg of body weight per day for three days (Rx-2) or intravenously administered clodronate disodium, 12 mg/kg of body weight given once only (Rx-3). By the third day of observation, Rx-2 produced a significant 2.8 mg/dL (0.70 mmol/L) reduction in serum calcium levels, whereas Rx-1 and Rx-3 did not produce a significant hypocalcemic effect when compared with baseline values. There were no toxicities observed. Intravenously administered clodronate appears to be an excellent agent for the acute treatment of malignancy-associated hypercalcemia.

Adult↗
PubMed1987

Angiosarcoma of the breast following segmental mastectomy complicated by lymphedema.

A patient is discussed who had angiosarcoma of her lymphedematous right breast develop four years after segmental mastectomy for infiltrating ductal carcinoma. The lymphedema developed and persisted after an indolent and recurrent postoperative infection. The possibility that the second malignancy is a consequence of the chronic lymphedema, similar to the angiosarcomas of lymphedematous extremities after radical mastectomy, is cautiously entertained. This hypothesis is worthy of consideration as more breast conservation surgery is being done, with or without adjuvant radiation therapy, and accumulating evidence suggests that lymphedema of the breast is a common complication of surgery followed by radiation.

Aged↗
PubMed1987

Maintenance etidronate in the prevention of malignancy-associated hypercalcemia.

Normocalcemic patients with cancer who had been successfully treated for an episode of hypercalcemia were enrolled in a randomized, multisite, double-blind, placebo-controlled trial designed to determine the efficacy of maintenance oral etidronate in preventing the recurrence of moderate to severe hypercalcemia (serum calcium level, greater than 11.5 mg/dL [greater than 2.87 mmol/L]). Ten (40%) of 25 etidronate-treated patients and 17 (46%) of 37 placebo-treated patients had recurrence of hypercalcemia within 150 days. Although patients taking etidronate had a longer time to the development of hypercalcemia (median, 55 days vs 28 days), this was not significantly different from the control group. The high attrition rate in this trial from hypercalcemia and other malignancy-related causes represents a major difficulty in conducting studies with agents that may require prolonged administration before producing a therapeutic effect.

Administration, Oral↗
PubMed1985

Modulation of 5-iodo-2'-deoxyuridine metabolism and cytotoxicity in human bladder cancer cells by fluoropyrimidines.

Iododeoxyuridine (IdUrd) potentiated the lethal but not the growth inhibitory properties of fluorouracil (FUra) and fluorodeoxyuridine (FdUrd) in human bladder cancer cells (T24). The rate of incorporation of IdUrd into DNA was enhanced by both fluoropyrimidines, but to a significantly greater extent by FdUrd. Both inhibition of iododeoxyridylate dehalogenation and the depletion of thymidine triphosphate pools contributed to the increased incorporation rate. Inhibition of dehalogenation accounted for 67% of the observed stimulation in the case of FUra, but only 37% of the increase produced by FdUrd. The depletion of dTTP pools, both in the presence and absence of IdUrd, was greater after FdUrd than FUra exposure. The observed increase in the rate of incorporation of IdUrd appears to account for the enhanced toxicity seen with FdUrd, but other factors may be involved in the case of FUra. Since FUra and IdUrd appear to be mutually potentiating and do not share a dependence on thymidine kinase activity, this drug combination warrants further investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Correlations between leukocyte count and absolute granulocyte count in patients receiving cancer chemotherapy.

The absolute granulocyte count (AGC) has been considered the best index for estimating the risk of infection in patients receiving myelosuppressive therapy. However, many investigators and cooperative oncology groups use the leukocyte count and extrapolate concurrent AGC values from an arbitrary conversion scale. Our review of the literature revealed no analysis of the relationship between the leukocyte count and the AGC in patients receiving cancer chemotherapy. It also failed to provide a method for converting toxicity criteria from one scale to the other. To explore the possible relationship of the leukocyte count to the AGC, we have completed a retrospective analysis of leukocyte count and accompanying AGC in patients receiving cancer chemotherapy. The leukocyte count and the AGC are shown to be linearly related over the entire population, enabling predictable cross-indexing from leukocyte count to AGC by the use of the formula: AGC = -0.7 + 0.8 (leukocyte count). This provides a rational basis for the development of guidelines for drug dosing and toxicity. In the patient group with leukocyte count less than or equal to 4500, however, the magnitude of random variability decreased predictive ability. Numerous patients in this group received differing toxicity scale scores when classified according to the Eastern Cooperative Oncology Group (ECOG) scales for AGC and leukocyte count. In some cases, as much as 46% disagreement occurred. New toxicity scales for AGC and leukocyte count, which were developed based upon the linear relationship above, reduced this disagreement substantially. These scales result in a greater agreement of toxicity ratings, and may provide a more accurate method of classifying toxicity and regulating dosages of chemotherapeutic agents.

Antineoplastic Agents↗
PubMed1984

Transient neurologic dysfunction following moderate-dose methotrexate for undifferentiated lymphoma.

Two patients, aged 24 and 19 years, who had undifferentiated lymphoma, developed the acute onset of focal neurologic deficits 10 days after treatment with moderate-dose methotrexate (2.76 g/m2 by 42-hour intravenous infusion) and 12.5 mg of intrathecal methotrexate. Prior chemotherapy also included intravenous cyclophosphamide, doxorubicin, vincristine, oral prednisone, and intrathecal cytosine arabinoside. Dysarthria with left hemiparesis was noted in one patient and inability to speak and quadriparesis in the other. Cerebrospinal fluid and cranial computerized tomography results were normal; however, EEGs showed focal abnormalities in both patients. Full neurologic recovery occurred within 48 hours. These symptoms developed early in the course of treatment and have not recurred in one patient who continued to receive the same regimen. The mechanism for this neurologic dysfunction is unclear. A similar picture has been reported in patients receiving high-dose methotrexate (8-10 g/m2) for osteogenic sarcoma.

Adult↗
PubMedDate not supplied

A phase II study of gemcitabine and cisplatin in patients with advanced hepatocellular carcinoma.

The primary objective of this study was to determine the response rates of a combination of gemcitabine and cisplatin in unresectable hepatocellular carcinoma (HCC) in Indian patients. The secondary objectives were to evaluate the toxicity, time to progressive disease and overall survival for this combination. Chemonaive patients with histopathologically proven, bidimensionally measurable, stage Ill or IV unresectable HCC were enrolled into this study. All the patients were required to have a Zubrod's performance status not greater than 2, should not have undergone prior radiotherapy and were required to have adequate major organ function. Patients received gemcitabine (1250 mg/m2 intravenously over 30 to 60 min) on days 1 and 8, and cisplatin (70 mg/m2 intravenously over 2 hours) on day land every 21 days. Response assessment was done by a Computed Tomography scan after every two cycles of chemotherapy. From May to December 1999, 30 patients were enrolled in the study; they were all eligible for efficacy and toxicity analysis. Six (20%) patients achieved a partial response and 13 (43%) patients demonstrated stable disease with 11 (37%) patients showing disease progression. The median time to progression was 18 weeks (range 1 to 74 weeks) and the median duration of response was 13 weeks (range 4 to 68 weeks). The 1-year survival rate was 27% and the median overall survival was 21 weeks (95% CI: 17 to 43 weeks). WHO grade 3 and 4 anemia was seen in 11 (37%) and 2 (7%) patients, respectively. Four (13%) patients each experienced grade 3 and 4 neutropenia and grade 3 and 4 thrombocytopenia was seen in 2 (7%) patients each. Major, non-hematologic toxicities were grade 4 elevated bilirubin levels and grade 3 oral toxicity, in 1 patient (3%) each. This regimen was well tolerated and did show activity in Indian patients with advanced unresectable HCC. There is a need to further evaluate this combination in order to define its role in the treatment of HCC.

Adult↗
PubMedDate not supplied

Phase I study of vinblastine and verapamil given by concurrent iv infusion.

Overcoming resistance to chemotherapy is an important goal in cancer treatment. In many systems, resistance to anthracyclines and vinca alkaloids correlates with a diminished intracellular content of drug. In P388 leukemia and Ehrlich ascites tumor, an active outward transport of anthracyclines and vinca alkaloids occurs. Calcium channel blockers, such as verapamil, inhibit this active outward transport and increase intracellular content of vinblastine and anthracyclines in cells resistant to vinca alkaloids and anthracyclines, respectively. We report a phase I trial of vinblastine (1.5 mg/m2 daily as iv continuous infusion X 5 days) in 17 patients and concurrent verapamil in escalating doses. Verapamil was administered as a loading dose (0.02-0.1 mg/kg) followed by a maintenance infusion (0.036-0.18 mg/kg/hour) for 5 1/2 days with continuous cardiac monitoring. There was no apparent augmentation of vinblastine toxicity when vinblastine and verapamil were given concurrently. ECG change was the dose-limiting toxicity. At 0.12 mg/kg/hour, five of nine patients developed first-degree heart block (mean P-R interval, 0.32 seconds; range, 0.23-0.52 seconds). Junctional rhythms were noted in two of 17 patients. Reversible nonspecific T-wave changes were seen in four of 17 patients. Blood pressure and left ventricular ejection fractions (ultrasonic) were not altered. Five of 17 patients had wbc count nadirs less than 2000/mm3, and two of 17 patients had platelet count nadirs less than 100,000/mm3. Four patients experienced neurotoxicity. A mean vinblastine concentration of 2.2 ng/ml (0.55 nM) and a mean verapamil concentration of 290 ng/ml (0.45 microM) were achieved with the concurrent 5-day infusion. The tolerable levels of verapamil obtained appear to be less than those which were reported to inhibit vinblastine efflux in vitro. Additional in vitro experiments at the tolerable doses of vinblastine and verapamil are recommended.

Adult↗
PubMedDate not supplied

Prognostic implications of c-Ki-ras2 mutations in patients with advanced colorectal cancer treated with 5-fluorouracil and interferon: a study of the eastern cooperative oncology group (EST 2292)

PURPOSE: Mutations in c-Ki-ras2 (ras) occur in about 40% of patients with colorectal cancers and occur early in the pathogenesis of this disease. To evaluate the prognostic value of mutations in ras, the Eastern Cooperative Oncology Group (ECOG) conducted a retrospective study (EST 2292) to determine the frequency of mutations in patients with advanced colorectal cancer, and to determine whether ras mutations were associated with altered response to therapy and survival. PATIENTS AND METHODS: Patients were enrolled from four studies: P-Z289, an ECOG phase II trial of 5-fluorouracil (5-FU) and interferon (IFN) in patients with advanced colorectal cancer; P-Z991, an ECOG phase I trial of 5-FU and IFN in patients with advanced malignancies; and two trials from the Albert Einstein College of Medicine in patients with advanced colorectal cancer treated with 5-FU and either IFN-alpha or IFN-beta. All patients had advanced colorectal carcinoma and had sufficient histologic material available for analysis for the presence and type of ras, using polymerase chain reaction and dot-blot analysis with sets of probes sufficient to detect all the common mutations of ras at codons 12, 13, and 61. RESULTS: Seventy-two patients were enrolled in this trial. Mutations in ras were detected in 25 (35%), including 17 (23%) in codon 12, four (6%) in codon 13, and four (6%) in codon 61. There was no correlation between the presence of a ras mutation and age, sex, Dukes' stage, histology, or tumor markers. Thirty-one of 72 patients (43%) responded to therapy with 5-FU and IFN, and 10 of 31 responders (32%) and 15 of 41 nonresponders (37%) had mutations in ras. There was no difference in response rates or overall survival between the groups with and without ras mutations. CONCLUSIONS: It is unlikely that ras mutations will have significant prognostic value for either response to therapy or survival in patients with colorectal carcinomas treated with 5-FU and IFN.

Adult↗