bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombopoietin: Biology and Clinical Applications
Authors: Kuter David J. 
Published: February 2020

Abstract
Thrombopoietin (also called c-Mpl ligand, megakaryocyte growth and development factor, megapoietin) has recently been purified and cloned. This molecule is indeed the long-sought-after hematopoietic factor that controls platelet production. Thrombopoietin levels increase within 24 h after the onset of thrombocytopenia and are inversely and exponentially proportional to the platelet count. Injection of thrombopoietin into animals stimulates the number, size and ploidy of bone marrow megakaryocytes and increases the platelet count up to ten-fold. Although human studies with several different forms of recombinant thrombopoietin have just begun, animal studies suggest a wide range of potential clinical applications. In animals, recombinant thrombopoietin reduced radiation- and chemotherapy-induced thrombocytopenia, enhanced platelet recovery after bone marrow transplantation and increased the number of megakaryocyte precursor cells in stem cell harvests. Active at very low concentrations, thrombopoietin appears to have few adverse effects in animals. At very high doses, reversible marrow fibrosis has occasionally been seen, but despite platelet counts up to ten times normal, there is no evidence that it increased the risk of thrombosis. There is little likelihood that thrombopoietin will stimulate tumor growth since receptors for thrombopoietin have not been detected on solid tumors. Therefore, thrombopoietin promises to be a specific and effective stimulator of platelet production and will soon join erythropoietin and G/GM-CSF in the clinical armamentarium. Although thrombocytopenia is uncommon in most chemotherapy protocols, ongoing clinical studies will determine the role of thrombopoietin in the prevention and treatment of thrombocytopenia in oncology patients.
Diagnosis and Treatment of Early-Stage Non-Small Cell Lung Cancer
Authors: Olak Jemi , Ng Arthur 
Published: February 2020

Abstract
Current recommendations for the diagnostic work-up and treatment of early-stage non-small cell lung cancer are presented, and the rationale behind these recommendations is reviewed. Early-stage disease is found in approximately 30% of patients at initial presentation. Surgeons continue to be uncertain with regard to how extensively they should look for metastatic disease, especially in asymptomatic patients with newly diagnosed lung cancer. While it is generally agreed that surgery is an important component of treatment for stage I and II non-small cell lung cancer, the role of adjuvant therapies in early-stage disease merits further study. Stage IIIa lung cancer is evolving as a disease for which multimodality therapy is likely to play a role, but the timing and sequence of treatment is an area of intense investigation. The recommendations made in this article are based upon the results of randomized clinical trials whenever possible.
Resistance Mechanisms to Methotrexate in Tumors
Authors: Bertino J.R. , Göker E. , Gorlick R. , Li W.W. , Banerjee D. 
Published: February 2020

Abstract
The mechanisms of intrinsic and acquired resistance to methotrexate (MTX) in human tumors are reviewed herein. In blasts from patients with acute lymphocytic leukemia, resistance mechanisms found are decreased uptake and increased dihydrofolate reductase (DHFR) activity. A major cause of intrinsic resistance to MTX in soft tissue sarcoma cells and in acute myelocytic leukemia appears to be a lack of drug retention, due mainly to low levels of polyglutamylation. A novel association between lack of the retinoblastoma protein and intrinsic MTX resistance has been found. This has been attributed to an increase in DHFR activity, due to an increased rate of transcription of this gene, stimulated by an increase in levels of free E2F, not sequestered by hypophosphorylated retinoblastoma protein.
From Plasma Kinetics to Cellular Pharmacology
Authors: Pinedo H.M. 
Published: February 2020

Abstract
This paper primarily summarizes the work done under the guidance of Dr. Bruce Chabner in 1975 and 1976. During these years I studied the role of drug concentration, duration of exposure, and endogenous metabolites in determining methotrexate (MTX) cytotoxicity to the bone marrow stem cell (CFU-C). We found that the rate of loss of CFU-C during continuous intravenous infusion of methotrexate was related to the duration of exposure until the nadir in cell count was reached at 24 hours. Depletion of nucleated cells was mitigated, probably as a result of recruitment of previously uncommitted precursor cells to CFU-C, even while the MTX infusion was continued up to 48 hours. In vitro it was shown that methotrexate and leucovorin were transported competitively in the CFU-C, which was in clear contrast with rescue agents such as thymidine and nucleoside analogs. After my training my work has continued in close contact with Dr. Chabner, while the scope of both our interests broadened to include the field of multidrug resistance (MDR). My own interest focused on functional studies in MDR.
Multiple Myeloma: An Overview in 1996
Authors: Kyle Robert A. 
Published: February 2020

AbstractMultiple myeloma (MM) has an incidence of approximately four per 100,000 per year. Ninety-nine percent of patients with MM have a monoclonal (M-) protein in the serum or urine during the course of their disease. MM must be differentiated from smoldering multiple myeloma (SMM), which has an M-protein value of more than 30 g/l and more than 10% plasma cells in the bone marrow, but no other features of MM. The plasma cell labeling index (PCLI) and the presence of circulating plasma cells in the peripheral blood help to differentiate monoclonal gammopathy of undetermined significance and SMM from MM. The current median duration of survival with chemotherapy is about three years. Patients with low PCLI and low β2-microglobulin values have a median duration of survival of approximately six years. Melphalan and prednisone produce an objective response in 50% to 60% of patients. Combinations of chemotherapy produce a higher response rate, but the survival rate is not different. Allogeneic bone marrow transplantation is associated with a mortality rate of 25% within six months and an actuarial survival rate of 28% at seven years. Autologous peripheral stem cell transplantation is applicable to more patients and is reported to produce a higher response rate and longer survival than chemotherapy, but most patients will eventually have relapse.
Somatostatin Receptors in the Diagnosis and Therapy of Neuroendocrine Tumors
Authors: Wängberg B. , Nilsson O. , Johanson V. , Kölby L. , Forssell-Aronsson E. , Andersson P. , Fjälling M. , Tisell L.-E. , Ahlman H. 
Published: February 2020

Abstract
The expression of somatostatin receptors in neuroendocrine tumors has facilitated the diagnosis and surgical treatment of patients with these tumors. After injection of a radiolabeled long-acting somatostatin analog, 111In-octreotide, scintigraphic tumor imaging can be performed as well as intraoperative tumor localization. During localization studies very high 111In concentration values were found in tumor tissues versus normal tissues, especially in carcinoid tumors and endocrine pancreatic tumors. Studies on such tumors in cell culture further indicated internalization of 111In into tumor cells, which is a prerequisite for a radiobiological effect from short range Auger and conversion electrons. Attempts to systemic radionuclide therapy via somatostatin receptors in patients with neuroendocrine tumors have been initiated.
Current Management of Patients with Ductal Carcinoma-in-Situ
Authors: Chabner Elizabeth , Schnitt Stuart , Harris Jay 
Published: February 2020

Abstract
Because of the wider use of screening mammography, ductal carcinoma-in-situ, or DCIS, once rare, is now diagnosed with increasing frequency. Important questions remain unresolved regarding the natural history, classification, and management of DCIS. Many physicians have assumed that DCIS is diffuse and regularly progresses to invasive cancer; therefore, they routinely recommend mastectomy. However, as we learn more about this lesion, it is now clear that in many cases the lesion is focal in extent, “premalignant,” and curable with local procedures short of mastectomy. In this review, we describe the current state of knowledge regarding the presentation, pathology, natural history, and management of DCIS.
Gemcitabine: Future Prospects of Single-Agent and Combination Studies
Authors: Moorsel Catharina J.A. , Peters Godefridus J. , Pinedo Herbert M. 
Published: February 2020

Abstract
Gemcitabine (2′,2′-difluorodeoxycytidine, Gemzar) is a deoxycytidine analog with excellent antitumor activity against a number of solid tumors. Gemcitabine needs to be activated by deoxycytidine kinase and other kinases to its triphosphate, gemcitabine triphosphate, which can be incorporated into RNA and DNA. The latter effect is considered to be responsible for its antitumor effect and causes masked chain termination and inhibition of DNA repair. This effect may be of importance for combination with DNA interacting agents. In phase I trials daily, twice weekly, weekly and every two weeks schedules have been evaluated. At the weekly schedule of 1,000-1,250 mg/m2 significant antitumor activity was observed in bladder, breast, ovary, and pancreatic cancer, non-small cell lung cancer (NSCLC), and small cell lung cancer of 31%, 33%, 22%, 11%, 22% and 27% total response rates, respectively. Gemcitabine also showed considerable improvement in clinical symptoms, while toxicity was not severe with mild myelosuppression. Due to its ability to inhibit DNA replication, combination studies were initiated with DNA damaging agents. For the various combinations with cisplatin in phase II studies on NSCLC, response rates varied from 42%-54%, with a median survival of generally more than 12 months. Also, combinations with taxanes, etoposide, doxorubicin and vindesin seem promising. Gemcitabine is an important agent for the management of several relatively chemoresistant cancer types, both with respect to antitumor activity and clinical benefit. Future research on combination studies deserves high priority considering the high response rates in NSCLC and bladder cancer.
Cancer of Unknown Primary Origin
Authors: Briasoulis Evangelos , Pavlidis Nicholas 
Published: February 2020

Abstract
About 3% of all cancer patients suffer from cancer of unknown primary origin. These patients present with metastatic disease for which a primary site cannot be detected at the time of diagnosis. Sophisticated diagnostic techniques and operational procedures have failed to improve the diagnostic efficacy in this group of patients. Consequently, a limited diagnostic procedure with basic laboratory tests and imaging studies is sufficient for the diagnosis of this syndrome. The use of immunohistochemistry, as well as serum tumor markers of high specificity that may help to identify other tumors, is highly suggested. Although the prognosis for the majority of these patients still remains poor, several subsets of favorable outcome to treatment have been recognized. Nevertheless, promising in vitro data and new drugs on trials, paralleled with a better knowledge of the underlying pathogenetic molecular mechanisms, offer a more optimistic look to the future therapeutic management of these patients.
Anti-Leukemia Chemotherapy of High-Risk Myelodysplastic Syndromes
Authors: Tohyama Kaoru , Tsutani Hiroshi , Wano Yuji , Iwasaki Hiromichi , Fukushima Toshihiro , Urasaki Yoshimasa , Kawai Yasukazu , Nakamura Toru , Yoshida Yataro , Ueda Takanori 
Published: February 2020

Abstract
We evaluated the outcome of anti-leukemia chemotherapy on 42 patients with the high-risk myelodysplastic syndromes (MDS)—refractory anemia with excess of blasts (RAEB), 8 cases; RAEB in transformation (RAEB-T), 18 cases; chronic myelomonocytic leukemia (CMMOL), 6 cases; and leukemic transformation of MDS, 10 cases. The median age was 67 (range 20 to 84). As a remission-induction therapy, 35 patients received low-dose chemotherapy, such as low-dose cytarabine infusion, and seven patients received high-dose combination chemotherapy. The complete remission (CR) rates of the low-dose chemotherapy group and the high-dose combination chemotherapy group were 29% and 57%, respectively, and the overall CR rate was 33%. The median survival durations after induction chemotherapy of the CR group (14 cases), the partial remission (PR) group (11 cases), and the non-remission (NR) group (17 cases) were 19 months, 8 months, and 3 months, respectively. As a post-remission consolidation chemotherapy, high-dose combination chemotherapy seemed to be superior to low-dose chemotherapy judging from the median CR duration (16 months versus 4 months), but a long-term disease-free survival is hardly expected, in contrast with results in cases of de novo acute myeloid leukemia.
Sequential Adriamycin and CMF in Metastatic Breast Cancer
Authors: Zambetti M. , Giacobone A. , Terenziani M. , Zucchinelli P. , Demicheli R. , Biasi S. , Piotti P. , Bartoli C. , Valagussa P. , Bonadonna G. 
Published: February 2020

Abstract
Purpose. To evaluate the clinical activity of a sequential treatment with Adriamycin followed by CMF (cyclophosphamide, methotrexate, fluorouracil) and the relative therapeutic contribution of the two drug regimens given at full conventional doses in metastatic breast cancer.
Patients and Methods. From August 1990 to February 1993, 44 patients with advanced breast cancer previously untreated with chemotherapy entered the study. Treatment consisted of the intravenous administration of Adriamycin (75 mg/m2 on day 1 every three weeks) for four cycles followed by intravenous CMF (cyclophosphamide, 600 mg/m2; methotrexate, 40 mg/m2; fluorouracil 600 mg/m2) on days 1 and 8 every four weeks for four total courses.
Results. In 41 evaluable patients, four cycles of full-dose Adriamycin were able to achieve an overall response rate of 75%, including 17% complete remissions. Four cycles of CMF administered after Adriamycin were able to increase tumor response in 64% of evaluable cases. At the end of the sequential treatment program, 78% of 41 patients achieved an objective remission and in 30% of them a clinical complete response was documented. Main side effects, i.e., leukopenia and gastrointestinal disturbances, were moderate and short-lasting. One patient died because of acute myocardial infarction.
Conclusion. In untreated metastatic breast cancer patients, the sequential administration of Adriamycin and CMF is highly effective at the expense of a moderate toxicity profile that allows high-dose intensity of both drug regimens. CMF treatment after upfront Adriamycin is able to exert a further therapeutic advantage.
Tropisetron versus Metoclopramide in the Control of Emesis in Far-Advanced Cancer
Authors: Mystakidou K. , Befon S. , Trifyllis J. , Liossi C. , Papadimitriou J. 
Published: February 2020

Abstract
The present study was conducted to assess the optimum treatment for nausea and vomiting in patients with far advanced cancer. More specifically, we studied patients with cancers that were too far advanced to benefit from chemotherapy or radiotherapy and whose nausea and vomiting were not due to drug intake, cranial, electrolytic, or metabolic causes. One hundred twenty patients who were under antiemetic medication with metoclopramide (MET) and suddenly presented with uncontrolled nausea and vomiting were randomized to three different therapeutic regimens: MET plus dexamethasone (DEX), MET plus tropisetron (TRO), and MET plus TRO plus DEX. Patient diary cards were used to assess nausea and vomiting. By the end of day 15, total control of vomiting was achieved in 24% of MET plus DEX patients, in 84% of MET plus TRO patients, and in 92% of MET plus TRO plus DEX patients. Total control of nausea was achieved in 18% of MET plus DEX patients, in 74% of MET plus TRO patients, and in 87% of MET plus TRO plus DEX patients. All antiemetic treatments were similarly well tolerated. TRO in combination with either MET or MET and DEX produced the best control of both nausea and vomiting.
Adjuvant Drug Treatment for Resectable Breast Cancer
Authors: Hudis Clifford A. , Norton Larry 
Published: February 2020

Abstract
Breast cancer is the most common life-threatening malignancy in Western women and the second most common cause of cancer-related death. A paradox in the care of patients with breast cancer is the observation that the majority appear to be curable at the time of initial surgery, yet a large number later experience relapse followed by death from disease. To combat this problem, systemic drug therapy in conjunction with surgery and radiation therapy is now standard for many patient subgroups. Standard medical treatment options include up to five years of tamoxifen for receptor positive amenorrheic patients, approximately six months of combination chemotherapy for younger patients and those who are receptor negative, and both in some patient subgroups. These interventions have a profound public health impact even though the majority of patients destined to recur do so even following “optimal” treatment. Further improvements are hoped for as a result of ongoing research involving the use of high-dose chemotherapy, dose-dense chemotherapy, and newer agents. Clinical trials testing these approaches offer the best chance to continue our progress and help to better define appropriate and standard treatment strategies for the future.
Outpatient Management of Febrile Neutropenia: Should We Change the Standard of Care?
Authors: Talcott James A. 
Published: February 2020

Abstract
The syndrome of fever and neutropenia is an iatrogenic complication of cytotoxic therapy for cancer. Because febrile neutropenia is associated with serious infection, patients with the syndrome are treated emergently with broad-spectrum, high-dose antibiotics. Recently, a differentiated approach to febrile neutropenia has been explored, based on assessment of risk. Prediction rules to identify low-risk patients were developed, and outpatient management of low-risk patients has been explored. Based on pilot studies and early randomized trials, some have called for a new standard of outpatient care. This article describes the scientific rationale for the current standard of care for febrile neutropenia; reviews the risk assessment studies; discusses the issues of safety, quality of life, and shifting of economic burdens arising when outpatient care is substituted for inpatient care—a change in practice patterns sweeping through acute care medicine with little scrutiny; and critically reviews the published trials of outpatient treatment of febrile neutropenia.
Guidelines for the Treatment of Recurrent and Metastatic Cervical Cancer
Authors: Friedlander Michael , Grogan Michelle 
Published: February 2020

Abstract

Learning Objectives
After completing this course, the reader will be able to:Describe the natural history and prognosis of patients with recurrent and/or metastatic cervical cancer.Be able to select appropriate treatment options for patients with recurrent cervical cancer.Be able to identify which patients with locally recurrent cervical cancer are potentially curable with pelvic exenterative surgery.Describe the role and limitations of chemotherapy in the treatment of patients with metastatic cervical cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Although there have been important advances in the management of women with cervical cancer, the optimal treatment for patients with locally recurrent and metastatic disease is still problematic, and there are relatively few randomized trials to guide treatment decisions. This paper reviews the approach to management of patients who relapse after primary treatment for cervical cancer. Patients who are still potentially curable with radical treatment are identified, and the various treatment strategies are discussed. However, most women are treated with palliative intent, and the literature on palliative management is reviewed together with the levels of evidence.
Epoetin Alfa 60,000 U Once Weekly Followed by 120,000 U Every 3 Weeks Increases and Maintains Hemoglobin Levels in Anemic Cancer Patients Undergoing Chemotherapy
Authors: Patton Jeffrey , Kuzur Michael , Liggett William , Miranda Fernando , Varsos Helen , Porter Lester 
Published: February 2020

Abstract

Learning Objectives
After completing this course, the reader will be able to:
List the recommendations in current clinical practice guidelines on epoetin alfa dosing and administration regimens for patients with cancer and chemotherapy-related anemia. Discuss the benefits associated with epoetin alfa therapy in cancer patients with anemia receiving chemotherapy, in terms of increased hemoglobin levels, lower transfusion needs, and improved quality of life. Explain how higher initial doses of once-weekly epoetin alfa followed by less frequent maintenance dosing with epoetin alfa in anemic cancer patients undergoing chemotherapy may be beneficial, both to the patient and to the health care provider.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit atCME.TheOncologist.com
Purpose. Epoetin alfa administered s.c. three times weekly or once weekly increases hemoglobin (Hb) levels, decreases transfusion requirements, and improves quality of life in anemic cancer patients receiving chemotherapy. This study assessed the feasibility of using higher initial doses of once-weekly epoetin alfa followed by less frequent maintenance doses to increase and then maintain adequate Hb levels in this population.
Materials and Methods. In this open-label, nonrandomized, pilot study, anemic (baseline Hb ≤11 g/dl) cancer patients undergoing chemotherapy received initial doses of epoetin alfa of 60,000 U s.c. once weekly to increase Hb levels by at least 2 g/dl, followed by 120,000 U s.c. every 3 weeks to maintain Hb levels. The maximum treatment duration was 24 weeks.
Results. The mean baseline Hb level was 10.1 ± 0.8 g/dl (n = 20). Once-weekly dosing resulted in mean Hb level increases of 1.0 ± 1.1 g/dl by week 4 and 2.9 ± 1.9 g/dl by week 8; 86% and 79% of patients evaluable at week 8 and week 12, respectively, demonstrated increases of at least 2 g/dl (target Hb level of ≥12 g/dl). Thirteen patients (65%) received at least one maintenance dose; the mean Hb level increased from 12.8 ± 1.1 g/dl before starting maintenance therapy to 13.3 ± 1.4 g/dl at the last maintenance week. Both dosage regimens were well tolerated.
Conclusions. Once-weekly epoetin alfa at a dose of 60,000 U effectively increased Hb levels by week 8; 86% of patients achieved rises of at least 2 g/dl or Hb levels ≥12 g/dl. Moreover, epoetin alfa at doses of 120,000 U every 3 weeks maintained or increased Hb levels. Results from this pilot study suggest that higher initial once-weekly dosing of epoetin alfa followed by less frequent maintenance dosing appears to be feasible for treating anemia in cancer patients undergoing chemotherapy. Further evaluation of these and other epoetin alfa dosage regimens is warranted.