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Biomedical subjects

B R Greenberg

Publications and source records attributed to B R Greenberg.

At least 19 recordsLinked to original sources

Phase II trial of trimetrexate for patients with advanced gastric carcinoma: an Eastern Cooperative Oncology Group study (E1287).

BACKGROUND: A Phase II study was conducted to evaluate the response, duration of response, and duration of survival of patients with measurable gastric carcinoma treated with trimetrexate (TMTX) who had not had prior chemotherapy. METHODS: Thirty-three patients with unresectable or metastatic gastric adenocarcinoma who had not received previous chemotherapy were treated with intravenous TMTX 12 mg/m(2) daily for 5 days. The dosage of TMTX was reduced to 8 mg/m(2) daily for 5 days for those who had received prior radiotherapy. The cycle was repeated every 3 weeks until disease progression or unacceptable toxicity occurred. RESULTS: Thirty-three patients could be analyzed with follow-up data. There was one Grade 5 (lethal) toxicity and four Grade 4 toxicities. Hematologic toxicity was the most common. The overall response rate was 21%, the overall median progression free survival was 2.7 months, and the overall median survival was 5.9 months for the entire cohort. No patients were alive at last follow-up. CONCLUSIONS: Though TMTX as a single agent has activity in gastric carcinoma with manageable toxicity, it cannot be recommended for routine use as a single agent due to the brief duration of response and median survival.

Adenocarcinoma↗

Sequential chemotherapy and radiotherapy for organ preservation in advanced resectable nonlaryngeal head and neck cancer.

Although there is no definite survival advantage to the use of sequential induction chemotherapy (CT) followed by radiotherapy (RT) in advanced resectable laryngeal cancer, this approach does succeed in preserving the larynx in many of these patients. The authors performed this study to analyze their results using a similar approach for patients with advanced resectable cancer located outside the larynx who would have required a total laryngectomy for oncologic or functional reasons. A retrospective study was performed at a single institution that included all patients with advanced resectable nonlaryngeal head and neck cancer treated with induction CT between January 1990 and August 1995. A total of 19 patients were included, with primary cancers located in the oropharynx in 14 patients, the hypopharynx in four, and the oral cavity and oropharynx in one. Eight patients had clinical stage III disease, and 11 patients had stage IV disease. Our treatment protocol consisted of two cycles of induction CT with cisplatin and 5-fluorouracil, followed by a third cycle of CT and subsequent RT in patients who achieved at least a clinical partial response (PR) after two courses of induction CT. Eighteen of 19 patients were evaluable for response. Overall, 13 patients (72%) had a major response (PR or CR) to induction CT at the primary site, and eight patients (57%) had a major response to chemotherapy in the neck. With a mean follow-up of 53 months (range, 24-71 months), the disease-specific survival was 57% for those patients with cancer of the oropharynx and oral cavity. In the subset of patients with hypopharynx cancer, 3 of 4 patients died of cancer despite achieving major response to induction CT. Organ preservation using sequential CT and RT for advanced resectable nonlaryngeal head and neck cancer is feasible, and the results in our experience with cancer of the oropharynx were similar to those reported for primary laryngeal cancer. Our limited experience using this protocol for cancer of the hypopharynx has been disappointing.

Adult↗

Hyposplenism from Mycobacterium avium complex infection in a patient with AIDS and immune thrombocytopenia.

We describe a patient with HIV-related immune thrombocytopenic purpura with known Mycobacterium avium complex (MAC) infection presenting with intracerebral hemorrhage associated with severe thrombocytopenia who failed splenectomy following unsuccessful trials of corticosteroids and intravenous immunoglobulin. His presplenectomy peripheral blood smear showed Howell-Jolly bodies and microscopic examination of his spleen demonstrated multiple granulomas with numerous acid-fast organisms replacing the normal splenic tissue. We postulate that splenic hypofunction secondary to overwhelming MAC infection contributed to the failure of the thrombocytopenia to promptly respond to splenectomy.

Acquired Immunodeficiency Syndrome↗

HIV-associated autoimmune hemolytic anemia complicated by pulmonary embolism following a red blood cell transfusion: case report and review of the literature.

BACKGROUND: Though positive direct antiglobulin tests are common in AIDS patients, overt hemolysis is rare. A hypercoagulable state has recently been recognized in these patients and may contribute to the thromboembotic complications previously reported in three patients with HIV-associated autoimmune hemolytic anemia. CASE REPORT: An AIDS patient with severe warm autoimmune hemolytic anemia developed a pulmonary embolus after a single red blood cell transfusion. CONCLUSION: There may be an increased risk of thromboembolism in AIDS patients with autoimmune hemolytic anemia who receive red blood cell transfusions, a concern we have previously raised. Prophylactic anticoagulation should be considered in this setting.

Adult↗

Aortic wall sarcoma with tumor emboli and peripheral ischemia: case report with review of literature.

Primary malignant tumors of the aorta are rare, only a handful of isolated cases having been described in the literature. Preoperative diagnosis of these tumors is more the exception than the rule. Diagnosis of aortic tumors is difficult as they can mimic many diverse conditions including atherosclerosis. We report a patient who presented with lower extremity claudication, renal infarction, and diffuse atherosclerosis and who was found to have tumor fragments in blood clots but no evidence of a primary tumor. Immunohistochemistry narrowed the differential diagnosis to a type of sarcoma. Six months later, he developed right flank pain due to a malignant fibrous histiocytoma that involved the abdominal aorta and that had initially manifested as tumor emboli.

Aortic Diseases↗

Treatment of advanced pancreatic adenocarcinoma with 5-FU, leucovorin, interferon-alpha-2b, and cisplatin.

Previous laboratory and clinical studies support the ability of interferon (IFN) to enhance the antitumor properties of chemotherapy agents, including cisplatin and 5-fluorouracil (5-FU). A phase I-II clinical trial was initiated to treat several tumor types with IFN-alpha-2b, cisplatin, 5-FU, and leucovorin (LV), given daily for 5 days of a 28-day cycle. Because of preliminary results, this was continued as a phase II trial in 18 patients with metastatic adenocarcinoma of the pancreas. Each treatment day consisted of IFN 5 million u/m2 s.c. (maximum, 10 million U), CDDP 20 mg/m2 i.v. over 1 h, LV 20 mg/m2 i.v.p., and 5-FU 250-275 mg/m2 i.v.p. All patients had measurable disease with no prior chemotherapy for metastatic disease, and all had an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Six of the 16 patients evaluable for response had partial responses (PRs) (37.5%) with a median response duration of 4 months, and all responding patients survived > or = 8 months. Median survival of all 18 treated patients was 5 months. Severe gastrointestinal toxicity (nausea, diarrhea, or requirement for i.v. hydration) was common. Grade 4 hematologic toxicity was seen in six patients. The response rate observed is promising and supports the concept that IFN may potentiate the effects of standard chemotherapy agents. However, the toxicities observed with this dosage schedule were considerable and further studies are needed to develop a less toxic regimen.

Adenocarcinoma↗

Recurrent venous thrombosis as the presenting manifestation of acute lymphocytic leukemia: leukemic cell procoagulant activity is not responsible for the hypercoagulable state.

The association of cancer with clinical abnormalities of blood coagulation, including superficial thrombophlebitis, deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC) is well-known, particularly in patients with solid tumors and acute promyelocytic leukemia (APL). Less commonly appreciated is the potential for the development of venous thromboembolic disease (TED) in patients with acute lymphocytic leukemia (ALL). Multiple mechanisms have been implicated for the activation of coagulation in these patients, with an emphasis on the contribution made by the procoagulant properties of the tumor cells themselves. We present two cases of patients with pre-B cell ALL, both of whom developed recurrent TED as the presenting manifestation of their leukemia and/or heralding relapse. The blast cells from one of the patients were studied for the presence of procoagulant activity (PCA) and by Northern blot analysis for tissue factor (TF) messenger RNA (mRNA). Neither PCA nor TF mRNA could be identified in highly purified populations of the lymphoblast cells. We conclude that recurrent TED can be a manifestation of ALL and that mechanisms other than the release of tumor cell procoagulants should be sought to explain the pathogenesis of thrombosis in some patients.

Adult↗

Polycythemia rubra vera.

PV represents a clonal disorder characterized by excessive erythropoiesis accompanied by low serum EPO levels. Two populations of erythroid progenitors have been identified in the BM of patients with PV. One population responds normally to EPO and the other, the malignant clone, is exquisitely sensitive to EPO. The latter phenomenon is regarded as the most readily accepted explanation for the pathophysiology of this disease, although other mechanisms have been proposed. Thrombohemorrhagiccomplications, which usually correlate with the hematocrit level, are the most important because of their frequency and severity. Preventing such complications represents one of the most important therapeutic goals. Diagnostic criteria have been established enabling an accurate diagnosis of PV, in which the majority of patients live an excess of 10 years. Some will develop a falling hematocrit secondary to PPMM, also termed the spent phase. Patients may also develop acute leukemia, which is increased in incidence if myelosuppressive therapy is used, compared with phlebotomies alone. The initial treatment is phlebotomy to an hematocrit of 45% or less. The studies of the PVSG have shown that chlorambucil produces excessive mortality from malignancy, and 32P and phlebotomy are associated with superior survivals which are equivalent. Because of the substantial risk of thrombotic complications, elderly patients, ie, those older than 70 years, should be treated initially with phlebotomy and myelosuppressive therapy, usually 32P. Hydroxyurea appears less leukemogenic than 32P or alkylating agents; however, recent reports have questioned this. IFN is a promising new agent which may become a standard form of therapy in the future.

Adult↗

Treatment of myelodysplastic syndromes with daily oral idarubicin. A phase I-II study.

BACKGROUND: Idarubicin, a new anthracycline analogue, is available in an oral preparation, and responses have been observed using relatively aggressive therapy in patients with myelodysplastic syndromes (MDS). The authors studied whether a chronic low-dose schedule would be effective but less myelotoxic. METHODS: Forty-two patients with MDS received daily low-dose oral idarubicin in 5-week courses that included 3 weeks of treatment, followed by a 2-week rest period. Doses were escalated when possible after the second course, and each patient was to receive six courses. RESULTS: Only one partial response was observed. Although no patient had fatal bone marrow toxicity, only eight patients received the full six courses, primarily because of myelosuppression. CONCLUSIONS: This schedule of oral idarubicin is relatively safe but produces fewer responses than are reported with the high-dose pulse regimens.

Administration, Oral↗

Empirical chemotherapy for adenocarcinoma of unknown primary tumor site.

It is evident that no chemotherapy regimen can be considered standard for patients with ACUP. If after careful evaluation, a patient does not belong to a subset of patients with a higher chance of response, then the low likelihood of response to systemic therapy and the potential for treatment-associated toxicities must be reviewed with the patient. Should a trial of chemotherapy be chosen, this must be attempted with close monitoring for toxicity and should be discontinued unless a clear response is observed after a set time period, eg, two cycles of therapy. An effort should be made to ascertain whether there is a clinical protocol available at a regional center for which the patient would be eligible. For patients treated in a noninvestigational setting, we suggest a regimen such as FAM because of its relative tolerability and ease of administration. The most promising avenue for further study, and hopefully for future clinical practice, is the more precise identification of factors associated with a clearly defined response rate (either higher or lower) than patients with ACUP in general. The utilization of newer pathological or in vitro techniques for the study of these tumors should be encouraged as part of clinical trials because they may increase the number of patients who belong to specific subsets of ACUP associated with well-characterized responses to appropriate chemotherapy.

Adenocarcinoma↗

The Clinical Oncology Career Development Award of the American Cancer Society. A 5-year evaluation.

BACKGROUND: In 1985, the American Cancer Society (ACS) replaced their Junior Faculty Clinical Oncology Program with the 3-year Clinical Oncology Career Development Award (COCDA). It was proposed that the longer duration and larger stipend of the COCDA would have a greater impact in encouraging promising young clinical oncologists to enter and remain in academic oncology. The COCDA was evaluated at this time to determine whether these goals had been achieved. METHODS: A questionnaire was sent to 104 of the total of 121 people who received awards in 1985, 1986, and 1987. RESULTS: A review of the 85 completed questionnaires showed that the COCDA had a significant impact on the recipients. Most have remained in academic settings and have flourished, as evidenced by their publication record and success in obtaining extramural funds, despite their clinical orientation. CONCLUSIONS: The COCDA has achieved its initial goals and will remain an important part of the professional education efforts of the ACS.

Authorship↗

Empiric chemotherapy in patients with carcinoma of unknown primary site.

Analysis of the results of chemotherapy in patients with carcinoma of unknown primary site is complicated by the small sizes of most treatment series and patient heterogeneity. Careful evaluation of clinical and pathologic information may identify patients with a relatively high likelihood of response to systemic therapy. This includes patients in whom immunohistochemical studies or electron microscopy, or both, suggest a likely tumor type responsive to systemic therapy, such as prostate cancer, lymphoma, or a neuroendocrine tumor. Clinical evaluation can also identify potentially responsive patients, particularly those with clinical features in common with the extragonadal germ cell tumor syndrome. For patients who do not fit into these more treatable categories, most combination chemotherapy programs have response rates of less than 30% and median survivals of less than one year. Randomized trials have not established any clearly superior chemotherapy program. Regimens containing both Adriamycin (doxorubicin) and mitomycin-C produce response rates of approximately 25% but are associated with the possibility of severe hematologic toxicity, and rarely a syndrome resembling the hemolytic-uremic syndrome. The choice between chemotherapy and supportive care only must be individualized, and the latter option is appropriate for many patients. More detailed clinical and pathologic analyses in conjunction with clinical trials, particularly employing newer diagnostic techniques, are vital to provide better prospective data from which to identify relevant clinical subsets that allow an estimate of an individual patient's likelihood of response and the suitability of systemic chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

The affective lability scales: development, reliability, and validity.

A self-report measure of changeable affect was developed, with a goal of identification of patterns of instability in mood. Scales measuring lability in anxiety, depression, anger, and hypomania, and labile shifts between anxiety and depression and hypomania and depression were constructed. These scales were then evaluated for internal consistency, retest reliability, score stability across samples, and for discriminant validity through assessment of association with measures of dysphoria and intensity of affect. The final versions of the scales are short scales that yield highly stable estimates of affect lability. It was noted that these scales are highly correlated in unselected students and it is believed that ongoing research with clinical populations will better allow for determination of the independence of these scales.

Adolescent↗

Managing malignant pericardial effusion.

The involvement of the pericardium by metastatic tumors is not uncommon, particularly in patients with lung cancer, breast cancer, lymphomas, leukemias, and melanomas. There are five therapeutic modalities for the treatment of malignant pericardial effusion, including pericardiocentesis, pericardial sclerosis, systemic chemotherapy, radiotherapy, and surgical treatment. The optimal treatment selection is dependent principally on a patient's life expectancy; responsiveness of the tumor to chemotherapy, irradiation, or both; and whether or not cardiac tamponade is present at diagnosis. The overall prognosis of patients with malignant pericardial effusion is primarily influenced by the extent and histologic features of the underlying cancer. Although this condition is usually incurable, a reasonable period of useful palliation can be obtained in most patients.

Combined Modality Therapy↗

Metastatic cancer with unknown primary.

Close cooperation between an experienced pathologist and oncologist is essential in the management of patients with unknown primary carcinoma. A comprehensive pathological examination is crucial and, with undifferentiated tumors, this will include immunohistology and/or electron microscopy. Ample properly processed tissue therefore must be provided. Time-consuming and costly radiographic and imaging studies should be avoided. No matter how extensive the evaluation, in a majority of cases, the primary site will never be found, so a selective search for treatable tumors is most appropriate and cost-effective. With adenocarcinomas, this will include prostate, breast, and ovary; for undifferentiated tumors, small cell bronchogenic carcinoma, lymphomas, and germ cell tumors. Table 4 summarizes recommended studies for diagnosing unknown primary undifferentiated or adenocarcinomas. Women with adenocarcinoma in axillary nodes without a primary site should be treated as having breast cancer. Estrogen and progesterone receptor assays are to be obtained on the axillary biopsy. High and midcervical nodes with metastatic squamous cell carcinoma can be treated effectively and, not infrequently, cured with surgery and radiation therapy, even if the primary site never is detected. If doubt remains, treatment should be selected that offers the best chance of significant palliation or cure--for example, cisplatin-based chemotherapy in possible extragonadal germ cell tumors.

Axilla↗