Karen H. Antman's research while affiliated with Boston University and other places

Publications (154)

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Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, is cured with conventional therapy in 70%. However, the 5-year survival for those who relapse is about 30%, and drops to about 15% for those with unfavorable histologies (alveolar/undifferentiated subtypes). We describe outcomes of 62 subjects receiving autologous blood/bone m...
Chapter
Breast cancer risk, diagnosis and stagingStandard dose adjuvant chemotherapyStandard-dose therapy for metastatic diseaseDevelopment of highdose therapy regimens for breast cancerRandomized trials in the adjuvant settingRandomized trials in metastatic diseaseAutologous HCT: special situationsAllogeneic HCT for breast cancerResearch directionsa
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The objective of this study was to estimate the time to treatment failure and survival rate of the three-drug combination of doxorubicin, cisplatin, and ifosfamide as primary and postoperative, adjunctive treatment for teenagers and adults with osteosarcoma (OS). Sixty-three eligible patients with nonmetastatic OS of the extremities were registered...
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Metastatic breast cancer has been a common indication for autologous hematopoietic stem cell transplantation (HSCT). Previous reports indicate 3-year survival and progression-free survival (PFS) rates after autotransplant to be about 30 and 15%, respectively. Most deaths are from recurrent disease. One potential cause for high relapse rates is graf...
Article
The current study was conducted to assess the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte-colony-stimulating factor (rhG-CSF), given in an outpatient setting, in the treatment of patients with unresectable malignant mesothelioma. Between September 1994 and September 1996, 41 patients with histologicall...
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The similarity between the mechanism of action between docetaxel and estramustine generated the hypothesis of synergistic antimicrotubule effects and cytotoxicity when the two agents are combined. In addition, it has been demonstrated that estramustine binds P-glycoprotein in vitro and, thus, may prevent the efflux of taxanes in tumors that over-ex...
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Based upon the hypothesis that prolonged exposure to the S-Phase specific agent topotecan would be more efficacious in the treatment of soft tissue sarcomas than a conventional 5-day schedule of the drug, the Southwest Oncology Group performed a Phase II trial of topotecan administered as a continuous infusion in adult patients with advanced soft t...
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This review discusses the development and uses of imatinib mesylate, a protein tyrosine kinase inhibitor useful in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors that was recently approved by the Food and Drug Administration. Imatinib targets platelet-derived growth factor receptor, inhibits the fusion product of...
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To assess survival of patients with metastatic breast cancer treated with high-dose chemotherapy (HDC) versus standard-dose chemotherapy (SDC). SDC in four Cancer and Leukemia Group B (CALGB) trials was compared with hematopoietic stem-cell support in patients from the Autologous Blood and Marrow Transplant Registry. Cox proportional hazard regress...
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High dose therapy for breast cancer remains controversial. Of the 15 randomized trials of high dose therapy in breast cancer reported to date, two South African studies have been discredited leaving 13 remaining studies. Mortality was consistently low, in the 0 to 2.5% range, except for the BCNU containing American Intergroup study, which had a 7.4...
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Purpose: Based upon the hypothesisthat prolonged exposure to the S-Phasespecific agent topotecan would be moreefficacious in the treatment of soft tissuesarcomas than a conventional 5-day scheduleof the drug, the Southwest Oncology Groupperformed a Phase II trial of topotecanadministered as a continuous infusion inadult patients with advanced soft...
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PURPOSE: To assess survival of patients with metastatic breast cancer treated with high-dose chemotherapy (HDC) versus standard-dose chemotherapy (SDC). PATIENTS AND METHODS: SDC in four Cancer and Leukemia Group B (CALGB) trials was compared with hematopoietic stem-cell support in patients from the Autologous Blood and Marrow Transplant Registry....
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New therapies require rigorous evaluation before they become part of routine clinical care. The process of evaluating new drugs and devices is well established. When a new approach to treatment is ready for human trials, a phase 1 study is conducted with small numbers of patients so that common treatment-related toxic effects can be identified rapi...
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'Now is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning'Winston Churchill in a speech to the Canadian Senate and House of Commons, December 30, 1941. In laboratory models of cancer, dose of cytotoxic chemotherapy correlates with curative therapy, while cumulative dose is associated with longer surv...
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Although arsenic can be poisonous, and chronic arsenic exposure from industrial or natural sources can cause serious toxicity, arsenic has been used therapeutically for more than 2,400 years. Thomas Fowler's potassium bicarbonate-based solution of arsenic trioxide (As(2)O(3)) was used empirically to treat a variety of disorders, and in 1878, was re...
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Data from 11 randomised studies on high-dose chemotherapy for breast cancer are currently available. Most investigators, patients and insurers would agree that the two discredited South African trials are uninterpretable, and that the Scandinavian trial (which compares one very high-dose cycle versus six escalated dose cycles) does not ask the ques...
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torical series, suggesting either patient selection or an effect of the "intermediate"-dose CBP. Importantly, fewer relapses have occurred in the high-dose arm, but survival in the two arms is similar, presumably because of the early toxic mortality of 7.4%. The Scandinavian trial compared three cycles of induction FEC followed by one high-dose cyc...
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The recent Breast Cancer Prevention Trial has shown that tamoxifen may prevent invasive breast cancer. We used a Markov model to estimate the long-term effects of chemoprevention with tamoxifen on survival, quality-adjusted survival, and health care costs. We used a hypothetical cohort of women with breast-cancer risk similar to that of participant...
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Érico Arruda, Alexandre Andrade dos Anjos Jacome, Ana Luiza de Castro Conde Toscano, Anderson Arantes Silvestrini, André Santa Bárbara Rêgo, Evanius Garcia Wiermann, Geraldo Felicio da Cunha, Heloisa Ramos Lacerda de Melo, Karen Mirna Loro Morejón, Luciano Zubaran Goldani, Luiz Carlos Pereira, Mariliza Henrique Silva, Mauro Sergio Treistman, Mônica...
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Biol Blood Marrow Transplant 2000;6(5):469-75.
Chapter
Normal bone marrow cells have little or no expression of the MDR p-glycoprotein product and are, therefore, particularly susceptible to killing by MDR-sensitive drugs such as the vinca alkaloids, anthracyclines, podophyllotoxins, and taxanes. In this report of a phase 1 clinical study performed at the Columbia-Presbyterian Medical Center, we demons...
Article
Recent randomized controlled trials have shown that tamoxifen and raloxifene may prevent invasive breast cancer. This decision analysis study compares the outcomes of chemoprevention with tamoxifen, raloxifene, or oral contraceptives with the outcomes of prophylactic surgery among women with high-risk BRCA1/2 mutations. We used a simulated cohort o...
Article
Of the 11 randomized trials for which data are available, most would agree that the 2 South African trials are uninterpretable and that the Scandanavian trial does not ask the question of high-dose therapy versus conventional-dose therapy. Only 2 of the 8 remaining studies randomized more than 200 patients (855 in the Dutch study and 783 in the Can...
Article
Breast cancer incidence and mortality have been stable or declining since about 1992, the first decline since statistics were available.1,2While screening has resulted in a higher percentage of patients with early stage disease and improved survival, mortality at 10 years exceed 60% for those with 10 or more involved lymph nodes or large primary tu...
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Women with breast cancer are the most frequent recipients of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autotransplants) in North America. Despite widespread use, controversy exists about the benefits of and appropriate patients for this therapy. To determine factors associated with disease progression or...
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This phase I dose-escalation study was performed to determine the tolerability of three-drug combination high-dose BCNU (B) (450 mg/m2), escalating-dose thiotepa (500-800 mg/m2) and etoposide (1200 mg/m2) in divided doses over four days in 22 adults with malignant primary brain tumors. Patients received G-CSF and hematopoeitic support with peripher...
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Sequential high-dose chemotherapy may increase the threshold dose of CD34+ cells necessary for rapid and successful hematologic recovery. There are limited data regarding the pharmacodynamics and threshold CD34+ cell dose required for engraftment following high-dose paclitaxel. To determine the dose of CD34+ PBPC sufficient for rapid engraftment, 6...
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The purpose of this study was to determine the outcome of high-dose therapy with autologous hematopoietic stem cell support (autotransplants) in men with breast cancer. We studied 13 men receiving autotransplants for breast cancer and reported to the Autologous Blood and Marrow Transplant Registry (ABMTR) by 10 centers. Six men had stage 2 breast c...
Article
To determine progression-free survival (PFS) and overall long-term survival for limited-stage small-cell lung cancer (SCLC) patients aged 60 years or younger who respond to first-line chemotherapy followed by high-dose combination alkylating agents (cyclophosphamide 5,625 mg/m(2), cisplatin 165 mg/m(2), and carmustine 480 mg/m(2)) with hematologic...
Article
To determine the survival benefit and cost-effectiveness of screening Ashkenazi Jewish women for three specific BRCA1/2 gene mutations. We used a Markov model and Monte Carlo analysis to estimate the survival benefit and cost-effectiveness of screening for three specific mutations in a population in which their prevalence is 2.5% and the associated...
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In theintervening years, a number of randomized studies havebeen completed that address important questions regardingthe role of high-dose therapy with stem-cell support (HDT)in the aggressive non-Hodgkin’s lymphomas (NHLs). Forthis reason, the original consensus conference organizersconvened a second International Consensus Conference onHigh-DoseT...
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The prognosis in patients with primary brain tumors treated with surgery, radiotherapy and conventional chemotherapy remains poor. To improve outcome, combination high-dose chemotherapy (HDC) has been explored in children, but rarely in adults. This study was performed to determine the tolerability of three-drug combination high-dose thiotepa (T) a...
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Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance me...
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Young Ashkenazi Jewish women or those from high-risk families who test positive for BRCA1 or BRCA2 mutant genes have a significant risk of developing breast or ovarian cancer by the age of 70 years. Many question whether they should have prophylactic surgical procedures, ie, bilateral mastectomy and/or oophorectomy. A Markov model was developed to...
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High-dose chemotherapy is increasingly utilized for the treatment of metastatic and high-risk breast cancer. Autologous Blood and Marrow Transplant Registry data reveal that a single high-dose cycle of chemotherapy with stem cell support can produce high complete response rates, with 10% to 20% of patients disease-free at 5 years. For patients with...
Article
Adjuvant chemotherapy for rhabdomyosarcomas, osteosarcomas, and Ewing's sarcomas is established, but remains controversial in other adult sarcomas. Of the 14 reported adjuvant studies, the largest study from the European Organization for Research and Treatment of Cancer showed a significant improvement in local control for adjuvant chemotherapy in...
Article
Although usually associated with asbestos exposure, a number of case reports have noted the occurrence of malignant pleural mesothelioma in patients who received radiotherapy (RT) to the thorax. The authors performed a retrospective cohort study utilizing 251,750 women registered with breast carcinoma in the Surveillance, Epidemiology, and End Resu...
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Malignant mesothelioma is a disease that is refractory to chemotherapy. Therefore, the objective of this multi-institutional, cooperative group Phase II trial was to determine the efficacy of dihydro-5-azacytidine (DHAC), a pyrimidine analogue, in the treatment of malignant mesothelioma. Forty-one patients with histologically confirmed malignant me...
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To identify trends in high-dose therapy with autologous hematopoietic stem-cell support (autotransplants) for breast cancer (1989 to 1995). Analysis of patients who received autotransplants and were reported to the Autologous Blood and Marrow Transplant Registry. Between January 1, 1989 and June 30, 1995, 19,291 autotransplants were reviewed; 5,886...
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Telomeres, or chromosome ends, are essential in maintaining chromosomal integrity. Telomeres consist of a short hexameric sequence, 3′-TTAGGG-5′, repeated in tandem arrays added to chromosomes by the ribonucleoprotein enzyme telomerase. In this study, we assessed whether penclomedine, a novel synthetic pyridine compound presently being evaluated in...
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The use of CFU-GM and CD34+ cell enumeration for assessing harvest quality and factors affecting peripheral blood progenitor cell (PBPC) harvest and engraftment were investigated in 45 women with high-risk and metastatic breast cancer scheduled for dose-intensive cyclophosphamide, thiotepa, and carboplatin (CTCb). PBPC were mobilized with standard...
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Treatment of malignant mesothelioma (MM) at an early stage results in increased survival. Cytologic examination of pleural effusions is one of the first diagnostic techniques attempted in these patients. The objective of this study was to define the role of cytologic examination of pleural fluid in facilitating early diagnosis. The medical records...
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Asbestos exposure is the major known risk factor for mesothelioma, but several case reports have suggested a link between radiation therapy and subsequent development of malignant mesothelioma. This report explores a possible association between radiation therapy for Hodgkin's disease and mesothelioma. Four cases of malignant mesothelioma were obse...
Article
BACKGROUND: The development of an optimized peripheral blood progenitor cell (PBPC) harvest protocol to provide support for repetitive chemotherapy cycles is described. STUDY DESIGN AND METHODS: PBPCs mobilized by cyclophosphamide plus granulocyte-colony-stimulating factor (G-CSF) were studied in 163 leukapheresis harvests from 26 lymphoma patients...
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An autologous bone marrow transplant regimen of ifosfamide, carboplatin, and etoposide (ICE) has been developed as treatment for certain malignancies. At maximum tolerated doses renal insufficiency precludes dose escalation. The objective was to examine whether measurement of plasma drug levels early during treatment would provide warning of renal...
Article
To compare the efficacy and safety of ciprofloxacin (CIP) and trimethoprim/sulfamethoxazole (TMS) for the prevention of bacterial infections in patients who received bone marrow transplantation (BMT) for the treatment of solid and hematopoietic neoplasms. Adult inpatients about to undergo BMT for lymphoma, leukemia, or solid tumors were enrolled on...
Article
Agents with broad cytotoxic activity, steep linear log dose-response relationships, relative non-cross-resistance, and nonoverlapping nonhematologic toxicities can be combined to create new high-dose combination regimens. We have previously reported phase I dose-escalation studies of ifosfamide, carboplatin, and the combination of the two. Etoposid...
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Folic acid antagonists are reported to have activity against mesothelioma. The Cancer and Leukemia Group B (CALGB) undertook this phase II study of the new antifolate, trimetrexate (TMTX), to evaluate its response rate and toxicity in chemotherapy-naive patients with malignant mesothelioma. Fifty-two patients were accrued to this protocol. Because...
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Intravenous-bolus etoposide has modest activity in sarcomas when given daily for 3–5 days. Low frequent doses theoretically inhibit topoisomerase II activity over a longer duration and have been reported to have increased activity in small-cell lung cancer. A phase I trial of oral etoposide resulted in partial responses in two patients with soft-ti...
Article
Intravenous-bolus etoposide has modest activity in sarcomas when given daily for 3-5 days. Low frequent doses theoretically inhibit topoisomerase II activity over a longer duration and have been reported to have increased activity in small-cell lung cancer. A phase I trial of oral etoposide resulted in partial responses in two patients with soft-ti...
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Escalating costs of health care delivery and the current constraints imposed by the federal budget deficit seriously threaten to compromise patient care and innovative biomedical research. Recent third-party refusal to cover some patients treated in protocols has had considerable impact on trial research. In addition, reimbursement for conventional...
Article
Doxorubicin alone or with dacarbazine (DTIC; AD) is considered the best available therapy for metastatic adult sarcomas. Ifosfamide is active in sarcomas that have failed to respond to a doxorubicin-based regimen. This study was designed to determine if ifosfamide added to doxorubicin and DTIC (ADI) significantly effects toxicity, response rate, an...
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We studied a multimodality approach using extrapleural pneumonectomy, chemotherapy, and radiotherapy in patients with malignant pleural mesothelioma. From 1980 to 1992, 52 selected patients, underwent treatment. Median age was 53 years (range, 33 to 69). Initial patient evaluation was performed by a multimodality team. Pathologic diagnosis was revi...
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Asbestos exposure constitutes the primary cause of pleural and peritoneal mesothelioma in humans. Risk relates to the duration and intensity of exposure. Thus, those exposed at younger ages are at higher lifetime risk. Families of asbestos workers exposed to asbestos on hair and clothing as well as to asbestos items brought home from the workplace...
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Although initially responsive to chemotherapy, patients with small-cell lung cancer (SCLC) almost invariably suffer relapse. Recurrent SCLC responds poorly to treatment. Previous trials using high-dose chemotherapy with bone marrow support have commonly used single agents or combined alkylating agents without chest radiotherapy. Among patients with...
Article
To determine the benefit of aggressive surgical therapy, we studied 77 consecutive patients presenting to our sarcoma registry with pulmonary metastases. Detailed follow-up was available on all patients; the median follow-up of the 13 long-term survivors was 72 months from the date of diagnosis of the primary tumor. Survival of these 77 patients wi...
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High dose chemotherapy with autologous bone marrow support (ABMT) can achieve prolonged relapse-free survival in relapsed lymphomas, leukemias, and certain solid tumors. The principal morbidity and mortality relate to the infectious complications that occur during the 3-4 week aplasia until the marrow autograft recovers. Progenitor cells can be mob...
Article
Bone marrow transplantation (BMT) is being increasingly used in a wide variety of diseases. During the period of re-engraftment the patient is particularly susceptible to a number of opportunistic infections which can radically affect acute morbidity and mortality. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) has be...
Article
The overall median survival of women with advanced or high-risk primary breast cancer has not changed with conventional chemotherapy. Regimens employing high-dose chemotherapy with autologous stem cell support (ABMT) have been developed with the hope of optimizing tumor response and increasing survival. Early phase I studies in women with advanced...
Article
The chemotherapeutic approach to advanced sarcomas of bone and soft tissue is reviewed. The most active single agents against osteosarcoma are doxorubicin (overall response rate, 21%), methotrexate (30% to 40%), cisplatin (25%), and ifosfamide (28%). Current multimodality treatment for Ewing's sarcoma consists of combination chemotherapy with doxor...
Article
High-grade astrocytomas are the most common primary malignant brain tumors in adults and constitute a significant cancer problem in the USA accounting for nearly 11,000 deaths annually. Despite improvements in neurosurgical techniques and radiotherapy, the prognosis of these patients remains dismal with median survivals of less than 1 year. Recent...
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Fifty-six patients with metastatic or recurrent soft-tissue sarcoma were evaluated by 67Ga-citrate imaging. Prior to entry on the therapy protocol, 52/56 (93%) patients had true-positive 67Ga studies. Two of four patients with liposarcoma, one of twelve with leiomyosarcoma and one with an epithelioid sarcoma had false-negative studies; 89/105 disea...
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We retrospectively reviewed the pulmonary toxicity of six high dose chemotherapy protocols using four chemotherapy regimens in the treatment of solid tumors. All protocols used either high dose cyclophosphamide or ifosfamide in combination with one to three additional chemotherapeutic agents. In each protocol autologous bone marrow was reinfused po...
Article
Adjuvant therapy is currently established in the treatment of osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma. Of the 12 reported randomized studies of adjuvant chemotherapy for soft tissue sarcoma, only 2 show a significant overall survival advantage for chemotherapy (the most important endpoint). In three randomized trials, the survival of the...
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Efforts to diminish the overall morbidity and mortality of malignancy have required a variety of strategies and a balanced national research agenda. The design of curative regimens against leukemia, lymphomas, testis cancer, and childhood malignancies is a tribute to the interactions between laboratory and clinical scientists. Laboratory models ill...
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Sarcomas arise primarily from mesenchymal structures at any site in the body, even within visceral stroma and neurovascular bundles. Sarcomas have been associated with prior radiation therapy, toxic exposures, and genetic conditions and soft tissue sarcomas have been distinguished from bone sarcomas. For localized soft tissue sarcoma, tumor grade i...
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Twenty-six oncology patients, 25 of whom received bone marrow transplants, were enrolled in a prospective, randomized, double-blinded, placebo-controlled trial assessing the efficacy of ciprofloxacin, 750 mg p.o. b.i.d., for preventing bacterial infections during prolonged neutropenia. Treatment was begun within 48 hr of initiation of chemotherapy...
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Trimetrexate, a lipophilic, 2,4-diaminoquinazoline derivative of methotrexate, enters cells by passive diffusion rather than via a transport system. Trimetrexate has shown promising activity in animal model systems. A total of 16 patients with metastatic soft-tissue sarcoma who had received only one prior chemotherapy regimen were treated with trim...
Article
Cyclophosphamide demonstrates enhanced tumoricidal activity with decreased bone marrow toxicity when given on a divided-dose schedule in certain animal models. A total of 22 patients presenting with refractory metastatic cancer were treated in a phase I trial of continuous infusion of cyclophosphamide over 96 h. Granulocytopenia of less than 500/mi...
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To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood ce...
Article
Seven patients with both melanoma and sarcoma were seen at the Dana Farber Cancer Institute (Boston, MA) over a 4-year period. Three had additional malignant neoplasms; one of these patients also had the hereditary cutaneous malignant melanoma, dysplastic nevus syndrome. These observations suggest the possibility of a biologic relationship between...
Chapter
In 1891 Brown-Sequard attempted to augment human bone marrow orally [1]. Over the next five decades allogeneic marrow was administered intramuscularly [2] and by intramedullary injection [3], before the intravenous route was found to be optimal in 1939 [4]. Between 1945 and 1965 the effects of total body radiotherapy were studied and the immunocomp...
Article
To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood ce...
Article
Eleven patients undergoing autologous bone marrow transplant (BMT) were studied prospectively using serial99Tcmsulphur colloid liver-spleen scintigraphy. Anterior lung/liver (L/L) and spleen/liver (S/L) uptake ratios were determined from baseline prechemotherapy scintiscans and from one to four additional studies performed between 1 day before (day...
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In two sequential trials, 154 patients were treated with dosages of ifosfamide, ranging between 8 and 18 g/m2 divided over 4 days, with mesna uroprotection. The first was a phase II efficacy trial in 125 advanced sarcoma patients (Antman et al: J Clin Oncol 7:126-131, 1989), while the second was a dose escalation trial involving 29 patients (Elias...
Article
The mesna, doxorubicin, ifosfamide, dacarbazine regimen produced a 47% response rate (including 10% complete responses) in 105 eligible adults with advanced sarcoma. The major dose-limiting toxicity was granulocytopenia. There was one toxic death from sepsis. Central nervous system and renal toxicity occurred infrequently, perhaps as a result of th...
Article
In a phase II trial of ifosfamide 2 g/m2 days 1 to 4 with mesna uroprotection in 124 patients who had previously failed treatment for sarcomas, 3% achieved a complete response (CR), and 18% had a CR or partial response (PR). In the subset of patients with soft-tissue sarcomas, the response rate for the 64 patients who received bolus administration...
Article
In vitro and in vivo studies with N,N',N''-triethylene-thiophosphoramide (thiotepa) alone and in combination with cyclophosphamide (CTX) were carried out using the MCF-7 human breast carcinoma cell line and the EMT6 mouse mammary carcinoma cell line. In vitro, survival curves were essentially linear. The cytotoxicity of thiotepa toward MCF-7 cells...
Article
Phase II trials of ifosfamide have been performed with standard doses of 5 to 8 g/m2/course. In this phase I study, 29 patients were treated with a 4-day continuous infusion ifosfamide to determine the maximum-tolerated dose and the nonhematologic dose-limiting toxicity. Autologous bone marrow support was to have been used for the subsequent dose l...
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1. Hypertension is a complication of autologous bone marrow transplantation when therapy includes multiple alkylating agents. We have sought to identify the factors underlying this hypertension. We measured weight, serum creatinine, plasma renin activity, aldosterone and digoxin-like immunoreactive factor (DL1F), by digoxin radioimmunoassay, in 18...
Article
To estimate the effects on health of occupational exposure to crocidolite, a highly toxic form of asbestos, we studied a cohort of 33 men who worked in 1953 in a Massachusetts factory that manufactured cigarette filters containing crocidolite fibers from 1951 to 1957. Twenty-eight of the men have died, as compared with 8.3 deaths expected. This inc...
Article
Hematopoietic growth factors have now been purified, cloned, and produced in bacteria and yeast. Those that are currently in clinical study include erythropoietin, GM-CSF, G-CSF, M-CSF (also called CSF-1), and multi-CSF (also called interleukin 3). Growth factor appear likely to enhance the recovery and function of circulating white cells after sta...
Article
Sarcomas (fleshy tumors) were distinguished from carcinoma (crab leg tumors) at the time of Hippocrates. Sarcomas are related embryologically to leukemias and lymphomas because all are thought to be malignancies of mesodermal embryologic origin. Neurosarcomas, however, are an exception, since they arise from tissue of neuroepidermal origin. Maligna...
Article
Cytogenetic analysis was performed on short-term cultures of primary tumor tissue obtained from five patients with pleural malignant mesothelioma. Clonal karyotypic abnormalities were detected in four patients, none of whom had received cytotoxic therapy prior to karyotypic evaluation. Recurring chromosomal changes included partial deletions of 1p...
Article
In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID). Starting doses of these drugs were 60, 7,500, and 900 mg/m2 divided over 72 hours by continuous infusion, respectively. Mesna was given for 84 to 96 hours at 2,500 mg...
Article
An error was made in the response rates in the report "Response to Ifosfamide and Mesna: 124 Previously Treated Patients With Metastatic or Unresectable Sarcoma" by Antman et al, published in the January 1989 issue (J Clin Oncol 7:126–131, 1989). The report should read: Abstract and Response section: "... 22 (patients) (18%) had a complete or parti...

Citations

... Etoposide has also been given in tablet form, but as a single drug at doses of 50 mg/m 2 daily it has shown no or low efficacy [86,87]. In per oral combinations, e.g. with trofosfamide, it may be more active, as discussed below. ...
... Since tumor cells become progressively resis-tant to chemotherapy treatment, increasing the doses of chemotherapy is one way to overcome this chemoresistance. But the chemotherapy doses used are limited because of their toxicity in healthy tissues, such as hematopoietic tissue [111][112][113]. Multidrug resistance (MDR1) gene, which encodes the P-glycoprotein (Pgp), is a transmembrane protein involved in the efflux of toxic substances out of the cell [114], inducing protection of these cells toward chemotherapeu-tic agents [115]. ...
... More recently cellular, chimeric antigen receptor modified T-cell (CAR-T) therapies offer potentially curative options, but even with this approach well over half of the patients that are able to receive this treatment will suffer relapse [30][31][32][33][34] . Allogeneic hematopoietic stem cell transplantation can induce long-term DFS by taking advantage of the graft-versuslymphoma (GvL) effect; however, this strategy is infrequently employed due to unacceptable rates of treatment-related mortality (TRM) and graft-versus-host disease (GvHD) [7][8][9] . To mitigate these toxicities, reduced-intensity conditioning (RIC) regimens were initially developed to facilitate allogeneic engraftment while diminishing TRM rates, allowing for the immunologic GvL effect to eradicate disease, but earlier studies demonstrated that rapidly progressive or bulky disease outpaced these beneficial effects 10,11 ...
... Therefore, the MTD and DI for infusional ifosfamide may be increased or decreased relative to bolus delivery depending on the duration of infusion. Although phase III trials of infusional versus bolus ifosfamide have not been carried out, one study did analyze a sequential group of patients receiving ifosfamide as a bolus and subsequent entries as an infusion in conjunction with a combination chemotherapy regimen for metastatic sarcoma and there was a higher response rate in the group receiving bolus ifosfamide [29]. ...