bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of a Primary Chemotherapy Regimen Combining Vinorelbine, Epirubicin, and Methotrexate (VEM) as Neoadjuvant Treatment in 89 Patients with Operable Breast Cancer
Authors: Van Praagh Isabelle , Cure Hervé , Leduc Bernard , Charrier Sabine , Le Bouedec Guillaume , Achard Jean-Louis , Ferriere Jean-Pierre , Feillel Viviane , Latour Monique , Dauplat Jacques , Chollet Philippe 
Published: August 2004

Abstract
Purpose. In order to improve the breast conservation rate for noninflammatory operable breast cancer stage II and IIIa, neoadjuvant chemotherapy containing vinorelbine, 25 mg/m2, epirubicin, 35 mg/m2, and methotrexate, 20 mg/m2, VEM, was administered days 1 and 8 every 28 days for six cycles.
Methods. From October, 1991 to April, 1996, 89 patients (median age 52 years, range 31-72; 68 stage II and 19 stage IIIa) received 519 cycles (median six) of VEM chemotherapy.
Results. Hematotoxicity was mild (World Health Organization grade 3-4 neutropenia in 28% of cycles for 22 patients, and anemia or thrombocytopenia &gt;grade 2) when it occurred, and there were no toxic deaths. The clinical objective response was 90% (28% complete response and 62% partial response). All patients underwent surgery: 77 (87%) had conservative and 12 (13%) had modified radical mastectomy, and 12 (14%) reached pathological complete response. At December, 2000, with a median follow-up of 86 months (39-100), 13 patients had relapsed, and five had died of metastatic disease. Median disease-free survival was 100 months (8.4 years) and median survival had not yet been reached.
5-HT3-Receptor Antagonists for the Treatment of Nausea and Vomiting: A Reappraisal of Their Side-Effect Profile
Authors: Goodin Susan , Cunningham Regina 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to: List the differences in side-effect profiles of the 5-HT3-receptor antagonists.Explain the potential issues of each 5-HT3-receptor antagonist in patients with cardiovascular disease.Understand the potential issues of each 5-HT3-receptor antagonist in patients with hepatic or renal impairment.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Nausea and vomiting can cause considerable distress and discomfort to patients undergoing chemotherapy, radiotherapy, or surgery. Several classes of antiemetic agents exist to combat these side effects, though the 5-HT3-receptor antagonists have become the first-line treatment choice for many cancer patients and are considered the “gold standard” in antiemetic therapy. Compared with the older generation antiemetic drugs, 5-HT3-receptor antagonists are effective, well tolerated, and associated with few side effects. However, emerging differences among these agents suggest that the incidence and/or intensity of adverse events should not be regarded as a class effect.
The side-effect profile of any supportive care therapy is particularly important in certain subgroups of patients, including pediatric patients and the elderly, as well as those suffering comorbid conditions, such as cardiovascular disease and renal or hepatic impairment. Indeed, dolasetron is associated with cardiovascular effects, and thus, should be used with extreme caution in patients who suffer from or may develop prolongation of cardiac conduction intervals. Ondansetron, on the other hand, is associated with a greater incidence of central nervous system side effects than either dolasetron or ondansetron, and pharmacokinetic parameters are affected in patients with hepatic impairment, thereby requiring dose adjustments.
Clinicians are encouraged to evaluate patients on an individual basis when choosing which 5-HT3-receptor antagonist to prescribe.
CA125 Response: Can it Replace the Traditional Response Criteria in Ovarian Cancer?
Authors: Guppy A.E. , Rustin G.J.S. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to: Determine in what situations measuring CA125 levels could alter patient management.Discuss with patients the pros and cons of measuring CA125 during follow-up of ovarian cancer.Define response or progression of ovarian cancer.Incorporate CA125 use into clinical trial design.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
CA125 is well established as an accurate and reliable means of monitoring response to treatment and confirming relapse in ovarian cancer patients. Its role in follow-up after initial treatment is less certain and the subject of a current clinical trial. Measuring response with computerized tomography scans is futile in the majority of patients, as disease is often nonmeasurable at presentation, e.g., ascites or peritoneal deposits, or all measurable disease has been removed at the time of surgery. Serial changes in CA125 can be used as a reliable indicator of disease response or progression so that patients can be classified as responding or progressing according to either standard or CA125 criteria. These precise definitions are currently being prospectively validated in conjunction with the new response evaluation criteria in solid tumor response guidelines and are being incorporated into all future clinical trials.
A Phase I Trial of Weekly Paclitaxel Plus Prolonged Oral Eniluracil/5-Fluorouracil in Patients with Refractory Malignancies
Authors: Jones Suzanne F. , Greco F. Anthony , Hainsworth John D. , Patton Jeffrey W. , Barton John H. , Willcutt Noel T. , Baker Margaret N. , McGuirt Paul V. , Levin Jeremey , Burris Howard A. 
Published: August 2004

Abstract
Purpose. This phase I study was conducted to determine the dose-limiting toxicity (DLT), maximum-tolerated doses, and recommended phase II doses of the combination of weekly intravenous paclitaxel and oral eniluracil/5-fluorouracil (5-FU).
Patients and Methods. Patients received paclitaxel i.v. over 1 hour weekly for four consecutive weeks of each cycle. Oral eniluracil/5-FU was administered orally twice daily for 28 consecutive days starting on day 1 of each cycle. Cycles were repeated every 35 days. Patients were accrued at six different dosing combinations. Weekly paclitaxel doses ranged from 60 mg/m2 to 80 mg/m2, and oral eniluracil/5-FU doses ranged from 8.0/0.8 mg/m2 to 11.5/1.15 mg/m2 twice daily.
Results. Thirty-seven patients received 126 cycles of therapy. Myelosuppression was minimal at all dose levels, with no grade 4 neutropenia or thrombocytopenia reported. DLT was reported in three out of six patients enrolled at the highest dose level and consisted of grade 3 diarrhea (two patients) and grade 3 mucositis (one patient). No DLTs were reported in patients enrolled at lower dose levels. One complete response and three partial responses were reported in patients with taxane-resistant metastatic breast cancer.
Conclusion. The combination of paclitaxel and eniluracil/5-FU was generally well tolerated. The recommended doses for further phase II testing are paclitaxel 80 mg/m2 i.v. weekly for 4 weeks plus eniluracil/ 5-FU 10.0/1.0 mg/m2 orally twice daily on days 1-28 with cycles repeated every 35 days.
Aberrant DNA Methylation in Lung Cancer: Biological and Clinical Implications
Authors: Zöchbauer-Müller Sabine , Minna John D. , Gazdar Adi F. 
Published: August 2004

Abstract
Genetic abnormalities of proto-oncogenes and tumor suppressor genes are well-known changes that are frequently involved in lung cancer pathogenesis. However, another mechanism for inactivation of tumor suppressor genes is coming more and more into focus. Epigenetic inactivation of certain tumor suppressor genes by aberrant promoter methylation is frequently observed in lung carcinomas and seems to play an important role in the pathogenesis of this tumor type. While genetic abnormalities are associated with changes in DNA sequence, epigenetic events may lead to changes in gene expression that occur without changes in DNA sequence. Recent findings demonstrate that aberrant methylation can also be detected in the smoking-damaged bronchial epithelium from cancer-free heavy smokers, suggesting that aberrant methylation might be an ideal candidate biomarker for lung cancer risk assessment and monitoring of chemoprevention trials. Moreover, in vitro studies demonstrate that methylation can be reversed by demethylating agents resulting in gene re-expression. This concept is currently under investigation in clinical trials. In summary, recent studies demonstrate that aberrant methylation may be the most common mechanism of inactivating cancer-related genes in lung cancer, occurs already in smoking-damaged bronchial epithelium from cancer-free individuals, can be reversed in vitro by demethylating agents, and may be a useful biomarker for lung cancer risk assessment.
Combining Radiotherapy with Gene Therapy (From the Bench to the Bedside): A Novel Treatment Strategy for Prostate Cancer
Authors: Teh Bin S. , Aguilar-Cordova Estuardo , Vlachaki Maria T. , Aguilar Laura , Mai Wei-Yuan , Caillouet James , Davis Maria , Miles Brian , Kadmon Dov , Ayala Gustavo , Lu Hsin H. , Chiu J. Kam , Carpenter L. Steven , Woo Shiao Y. , Grant Walter H. , Wheeler Thomas , Thompson Timothy C. , Butler E. Brian 
Published: August 2004

Abstract
Combined radiotherapy and gene therapy is a novel therapeutic approach for prostate cancer. There are various potential benefits in combining ionizing radiation with gene therapy to achieve enhanced antitumor effects: A) ionizing radiation improves transfection/ transduction efficiency, transgene integration, and possibly, the “bystander effect” of gene therapy; B) gene therapy, on the other hand, may interfere with repair of radiation-induced DNA damage and increase DNA susceptibility to radiation damage in cancer cells, and C) radiotherapy and gene therapy target at different parts of the cell cycle. Preclinical data have demonstrated the enhanced antitumor effects of this combined approach in local tumor control, prolongation of survival, as well as systemic control. This combined radio-gene therapy is under study in an ongoing clinical trial in prostate cancer. Our study adds gene therapy to the standard of care therapy (radiotherapy). These treatment modalities have different toxicity profiles. The goal of this combined approach is to enhance cancer cure without an increase in treatment-related toxicity. This approach also offers a new paradigm in spatial cooperation, whereby two local therapies are combined to elicit both local and systemic effects. Early clinical results showed the safety of this approach.
The Molecular Perspective: Cadherin
Authors: Goodsell David S. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to: Gain a basic understanding of the structure and function of cadherins and their role in cancer metastasis.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
FDA Drug Approval Summaries: Fulvestrant
Authors: Bross Peter F. , Cohen Martin H. , Williams Grant A. , Pazdur Richard 
Published: August 2004

Abstract
Patients with hormone-sensitive breast cancer who have responded to tamoxifen may receive additional benefit from a second endocrine agent following progression or relapse after tamoxifen therapy. Fulvestrant (Faslodex®, ICI 182780, AstraZeneca Pharmaceuticals; Wilmington, Delaware) is a selective antagonist of estrogen designed to have no estrogenic effects. Lack of aqueous solubility led to the development of a parenteral formulation for monthly intramuscular administration. Fulvestrant has been shown to inhibit the proliferative effects of estrogen on sensitive tissues in vitro and in vivo, and is without apparent measurable estrogenic activity. The data upon which marketing approval for fulvestrant was based are summarized below. Eight hundred fifty-one postmenopausal women with advanced breast cancer were enrolled in two phase III studies, 400 in a North American double-blind study and 451 in a European open-label study, comparing the efficacy and safety of fulvestrant with anastrozole. Four hundred twenty-eight patients were randomized to receive fulvestrant 250 mg monthly by intramuscular injection and 423 patients were to receive anastrozole 1 mg daily. Patients were considered hormone sensitive either by receptor status or previous response to endocrine therapy. Over 96% of patients had previously received tamoxifen, either in the adjuvant setting or as treatment for metastatic disease. The primary study end points were response rate and time to progression. Response rates for patients treated with fulvestrant were 17% and 20% in the North American and European trials, respectively, compared with 17% and 15% in the anastrozole treatment arms. There were no statistically significant differences in response rates, time to progression, or survival between treatment arms in either study. The most common adverse events attributed to the treatment (&gt;10%) were injection-site reactions and hot flashes. Common events (1%-10%) included asthenia, headache, and gastrointestinal disturbances (nausea, vomiting, and diarrhea), as well as rash and urinary tract infections. A small increase in joint disorders was reported in the anastrozole-treated patients. On April 25, 2002, fulvestrant 250 mg by monthly intramuscular injection was approved by the U.S. Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Approval was based on similarity of response rates and time to progression between fulvestrant and anastrozole.
The Use of Zoledronic Acid, a Novel, Highly Potent Bisphosphonate, for the Treatment of Hypercalcemia of Malignancy
Authors: Major Pierre 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:Recognize the natural history and clinical presentation of hypercalcemia of malignancy (HCM).Compare the relative efficacy of available bisphosphonates in the treatment of HCM.Examine the efficacy and safety of zoledronic acid, a new-generation bisphosphonate.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Background. Hypercalcemia of malignancy is a serious complication of cancer that affects patients with and without bone metastases. A single infusion of pamidronate disodium, a nitrogen-containing bisphosphonate, effectively normalizes serum calcium in the majority of patients treated for up to 1 month. Zoledronic acid is a new-generation, heterocyclic nitrogen-containing bisphosphonate and the most potent inhibitor of bone resorption identified to date.
Methods. The natural history, clinical presentation, and treatment of hypercalcemia of malignancy are reviewed, with a focus on the mechanisms of action and relative efficacy and safety of bisphosphonate therapies.
Results. The improved efficacy of zoledronic acid compared with pamidronate disodium has been demonstrated in a pooled analysis of two randomized clinical trials in patients with hypercalcemia of malignancy. In these trials, both zoledronic acid and pamidronate disodium were safe and well tolerated; however, zoledronic acid treatment resulted in a significantly higher number of complete responses, more rapid calcium normalization, and more durable responses compared with pamidronate disodium.
Conclusions. Given the superior efficacy and comparable safety profile of zoledronic acid compared with pamidronate disodium, zoledronic acid is likely to become the treatment of choice for hypercalcemia of malignancy.
A Dose-Escalation Study of Weekly Topotecan, Cisplatin, and Gemcitabine Front-Line Therapy in Patients with Inoperable Non-Small Cell Lung Cancer
Authors: Guarino Michael J. , Schneider Charles J. , Grubbs Stephen S. , Biggs David D. , Himelstein Andrew L. , Hogaboom Kurt , Tilak Samir 
Published: August 2004

Abstract
Purpose. To determine the optimal dose of combination topotecan, cisplatin, and gemcitabine in advanced non-small cell lung cancer patients.
Materials and Methods. This single-center, single-practice, phase I trial enrolled chemotherapy-naïve patients with inoperable stage IIIB/IV disease. Initial treatment was topotecan (0.5-2.0 mg/m2), cisplatin (20 mg/m2), and gemcitabine (1,000 mg/m2) on days 1, 8, and 15 of a 28-day cycle. Dose-limiting thrombocytopenia at week 3 necessitated less frequent gemcitabine dosing (days 1 and 15 of each cycle). Thereafter, topotecan dose escalation proceeded to the target dose of 2 mg/m2.
Results. Thirty patients were enrolled and evaluable for toxicity assessment. Treatment was extremely well tolerated: only one grade 4 adverse event (leukopenia); no hospitalizations for treatment-related toxicities; no fever/neutropenia. Although no dose-limiting toxicities developed, 1.75 mg/m2 topotecan is considered optimal and recommended for further study because it was well tolerated, active, and did not require dose adjustments or delays in therapy. Eleven of 29 (38%) evaluable patients achieved a partial response. Median survival was 38 weeks (range 4-110 weeks), median progression-free survival was 17 weeks, and the 1-year survival rate was 33%. Two patients remain alive after 108-122 weeks of follow-up.
Conclusion. A 28-day cycle of topotecan (1.75 mg/m2 days 1, 8, 15), cisplatin (20 mg/m2 days 1, 8, 15), and gemcitabine (1,000 mg/m2 days 1, 15) was a safe and well-tolerated outpatient treatment for advanced non-small cell lung cancer. The favorable preliminary efficacy and safety of this regimen suggest that further study in phase II trials, including quality-of-life end points, is warranted.
Improvement of Oral Drug Treatment by Temporary Inhibition of Drug Transporters and/or Cytochrome P450 in the Gastrointestinal Tract and Liver: An Overview
Authors: Kruijtzer C.M.F. , Beijnen J.H. , Schellens J.H.M. 
Published: August 2004

AbstractThe oral bioavailability of many cytotoxic drugs is low and/or highly variable. This can be caused by high affinity for drug transporters and activity of metabolic enzymes in the gastrointestinal tract and liver. In this review, we will describe the main involved drug transporters and metabolic enzymes and discuss novel methods to improve oral treatment of affected substrate drugs. Results of preclinical and clinical phase I and II studies will be discussed in which affected substrate drugs, such as paclitaxel, docetaxel, and topotecan, are given orally in combination with an inhibitor of drug transport or drug metabolism. Future randomized studies will, hopefully, confirm that this strategy for oral treatment is at least as equally effective and safe as standard intravenous administration of these drugs.
A Phase II and Pharmacokinetic Study of Ecteinascidin 743 in Patients with Gastrointestinal Stromal Tumors
Authors: Ryan David P. , Puchalski Thomas , Supko Jeffrey G. , Harmon David , Maki Robert , Garcia-Carbonero Rocio , Kuhlman Caroline , Winkelman Jennifer , Merriam Priscilla , Quigley Travis , Jimeno Jose , Manola Judith , Demetri George D. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe the mechanism of action, administration, and pharmacokinetics of ecteinascidin 743. Recognize the classification and pathophysiology of gastrointestinal stromal tumors. Appreciate that conventional cytotoxic chemotherapy has no efficacy in patients with gastrointestinal stromal tumors and that STI571 has dramatic efficacy.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Purpose. To assess the efficacy, tolerability, and pharmacokinetics of ecteinascidin 743 (ET-743) in patients with advanced gastrointestinal stromal tumors (GISTs).
Patients and Methods. The study was confined to adult patients with radiographically measurable GISTs. ET-743 was administered as a 24-hour continuous i.v. infusion at a dose of 1.5 mg/m2 repeated every 3 weeks. Pharmacokinetic blood sampling was performed during the first cycle of therapy. Tumors were restaged after every second cycle of therapy.
Results. A total of 20 patients was enrolled in the study, 19 of whom were treated with 47 cycles of ET-743 (median 2, range 1-10). Severe toxicities were limited to reversible grade 3 transaminitis in 10 patients and grade 3 fatigue in one patient. There were no objective responses, and disease stabilization occurred in two patients lasting for periods of 4 and 10 months. The 1-year survival rate was 71.1%. Mean ± standard deviation values of the maximum plasma concentration and total plasma clearance were 1.1 ± 0.4 ng/ml and 44 ± 16 l/h/m2, respectively, for 19 of the 20 patients.
Conclusion. This study is the first report of a prospective phase II trial to evaluate a cytotoxic agent in patients with GISTs. This study underscores the primary resistance of GISTS to chemotherapy and stands in stark contrast to the encouraging results recently achieved with STI571. The lack of response may be associated with a therapeutically ineffective exposure to the drug based upon the lower incidence of severe toxicities and greater clearance than described in phase I and II trials of ET-743.
Controversies Regarding the Use of Radiation After Mastectomy in Breast Cancer
Authors: Buchholz Thomas A. , Strom Eric A. , Perkins George H. , McNeese Marsha D. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:Explain the potential benefits of delivering radiation after mastectomy for patients with breast cancer.Provide a list of appropriate indications for selecting which patients would benefit from radiation after mastectomy and chemotherapy.Appreciate how radiation can potentially cause cardiovascular injuries and understand the importance of radiation technique in minimizing the risk for such injuries.Appreciate how immediate breast reconstruction can affect the delivery of postmastectomy radiation.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Despite years of clinical study, there are still many unanswered questions regarding postmastectomy radiation. It is clear that radiation therapy plays a critical role in the multidisciplinary management of patients with locally advanced or inflammatory breast cancer. It is also accepted that postmastectomy radiation is not required for most women with noninvasive disease or stage I disease. Randomized clinical trials studying radiation treatments for women with stage II or III breast cancer have shown that the addition of radiation after mastectomy can reduce local-regional recurrence rates, which then improves survival. However, other data have indicated that the risk of local-regional recurrence after mastectomy and chemotherapy is low for patients with small tumors and one to three positive lymph nodes, leading some to question whether postmastectomy radiation is useful for this group. A second controversy regards the sequencing of postmastectomy radiation and breast reconstruction. In this article we discuss these controversies, review the data that are relevant, and provide our institutional approaches to these issues.
Breast Cancer in the Very Young Patient: A Multidisciplinary Case Presentation
Authors: Mintzer David , Glassburn John , Mason Bernard A. , Sataloff Dahlia 
Published: August 2004

Abstract
A case is presented that exemplifies many issues and controversies in the diagnosis and treatment of breast cancer in the very young. This woman was 22 years of age at diagnosis; she initially underwent breast-conservation therapy and adjuvant chemotherapy, retained fertility, had a subsequent uncomplicated pregnancy and delivery, and 7 years later developed a local recurrence in the breast. The discussion addresses risk factors, diagnosis, and treatment of breast cancer in the young; the impact of treatment on fertility; implications regarding pregnancy, and the management of local recurrence after breast conservation.