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Future Directions of Monoclonal Antibody Use in Personalized Lung Cancer TherapyWith the new direction in research and clinical trials, treating patients who most benefit from treatment with minimal toxicity will continue to be the mainstay of personalized cancer therapy.
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UFT/Leucovorin Plus Weekly Paclitaxel in the Treatment of Solid TumorsThe palliation of symptoms and improvement of quality of life are important aspects of therapy in patients with incurable metastatic cancer. This article describes the preliminary results of a phase I study of uracil and tegafur, an orally available fluorouracil (5-FU) derivative combined with oral leucovorin plus weekly intravenous paclitaxel.
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Urothelial and Kidney CancersThis management guide covers the treatment of urothelial cancers (carcinomas of the bladder, ureters, and renal pelvis) and kidney cancers (renal tumors).
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Therapeutic Radiation in Patients With a Rising Post-Prostatectomy PSA LevelI agree with Drs. Forman and Velasco that the optimal management of patients with an elevated prostate-specific antigen (PSA) level after prostatectomy remains to be determined. The broader issue, however, is optimizing the management of post-prostatectomy patients who are at risk for recurrence. Hence, the dilemma: Should we wait for a chemically apparent recurrence before instituting treatment? Or, should we, on the basis of available information, quantify the risk of recurrence and the possible side effects of therapy and determine whether or not adjuvant radiotherapy is warranted based on the risk/benefit ratio?
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Advancing CML Management Towards an Ideal Patient JourneyThe panel concludes its discussion with insights on challenges and unmet needs in the CML treatment landscape, highlighting ways to better support patients and caregivers.
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Overview of Phase I/II Pemetrexed StudiesPemetrexed (Alimta) is an antifolate that is effective in the inhibitionof multiple enzyme targets including thymidylate synthase,dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase.The compound has been evaluated in several phase I trials, bothas single agent and in combination with other cytotoxic agents. Theinitial schedule selected for further investigation in phase II trials waspemetrexed 600 mg/m2 as a 10-minute infusion on day 1 every 21 days.During the subsequent phase II development, the dose of pemetrexedwas adjusted to 500 mg/m2 due to bone marrow and gastrointestinaltoxicities. The adjusted dose of pemetrexed was well tolerated throughoutthe late-phase drug development program. Preclinical evidencesuggests that pemetrexed has additive or synergistic activity when combinedwith many other clinically important anticancer agents, includinggemcitabine (Gemzar), fluorouracil, carboplatin (Paraplatin),oxaliplatin (Eloxatin), paclitaxel, and vinorelbine (Navelbine). Doselimitingtoxicities in these studies were primarily hematologic, and therewas no evidence of cumulative hematologic toxicity. During the drugdevelopment program it was discovered that supplementation with folicacid and vitamin B12 profoundly increased the tolerability ofpemetrexed. The studies discussed in this review demonstrate thatpemetrexed is well tolerated as a single agent and will be an importantcontribution to combination chemotherapy regimens.
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PARP Inhibitors in Breast Cancer: BRCA and BeyondThe aim of this article is to review the preclinical data and rationale for PARP inhibitor use in the aforementioned settings, as well as the current status of the clinical development of these agents in the treatment of breast cancer, along with future directions for research in this field.
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Irinotecan in Relapsed or Refractory Non-Hodgkin’s LymphomasBecause irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a broad spectrum of antitumor clinical activity, we investigated its activity in relapsed or refractory non-Hodgkin’s lymphomas (NHLs). Irinotecan at 300 mg/m² IV was administered every 21 days with intensive loperamide management of diarrhea.
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Is Surgery Always Necessary in Rectal Cancer?In this article, we review risks and benefits of the standard treatment approach for rectal cancer and compare standard treatment with alternative methods aimed at rectal preservation.
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UFT in Combination as Adjuvant Therapy for Breast CancerBetween 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a
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UFT in Combination as Adjuvant Therapy for Breast CancerBetween 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a
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UFT/Methotrexate/Leucovorin for Breast Cancer Patients in Progression After HDCT/PBPC SupportTwenty-four patients with metastatic breast cancer that had progressed after high-dose chemotherapy with peripheral blood progenitor cell (PBPC) support were given intramuscular methotrexate in combination with oral
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HER2 Overexpression and Paclitaxel Sensitivity in Breast Cancer: Therapeutic ImplicationsOverexpression by the HER2 gene plays a significant role in breast cancer pathogenesis, and the phenomenon is commonly regarded as a predictor of a poor prognosis. HER2 overexpression has been linked to sensitivity and/or resistance to hormone therapy and chemotherapeutic regimens, including CMF (cyclophosphamide, methotrexate, and fluoro-uracil) and anthracyclines. Studies of patients with advanced disease demonstrate that, despite the association of HER2 overexpression with poor prognosis, the odds of HER2-positive patients responding clinically to taxanes were greater than three times those of HER2-negative patients. Further studies in preclinical models used combination therapy for breast cancer cells that overexpress HER2, and the use of agents that interfere with HER2 function plus paclitaxel (Taxol) resulted in significant antitumor effects. [ONCOLOGY 11(Suppl):43-48, 1997]
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Commentary (Botet): Management of Malignant Biliary Obstruction: Nonoperative and Palliative TechniquesThere has been a significant accumulation of collective experience with percutaneous biliary drainage (PCD) during the past 20 years. As experience with the technique has increased, its role has undergone a series of redefinitions, although early enthusiasm for percutaneous drainage has been tempered by the realities of numbers and statistics.
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The Era of Immuno-Oncology: Are We There Yet?The next few years hold great promise, as new agents emerge and others consolidate their place on our shelves. We will be forced to rethink strategies and redefine management as a new era of immuno-oncology dawns.
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Nonoperative Strategies for Rectal Cancer Following a Complete Clinical Response to Preoperative Chemoradiation: A Few ConsiderationsAlthough the current standard treatment for patients with locally advanced rectal cancer is preoperative chemoradiotherapy followed by total mesorectal excision, concerns have been raised over the functional sequelae and possible overtreatment of rectal cancer patients.
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Molecular Staging of Prostate Cancer: Dream or Reality?Dr. de la Taille and colleagues from Columbia University provide an overview of the concept of molecular staging” of prostate cancer using reverse transcriptase–polymerase chain reaction (RT-PCR). They do an admirable job of summarizing all of the currently available data on the results of this assay in the clinical staging of prostate cancer. As they note, only their group and one other have been able to demonstrate that a positive assay correlates with final pathologic stage. A limited number of other studies have suggested that the RT-PCR assay can predict prostate-specific antigen (PSA) recurrence.
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Oropharyngeal and Oral Cavity Cancer Surgical Practice GuidelinesThe Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative evaluation for extent of disease, and role of the surgeon in
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The Promise of Pharmacogenomics: Gemcitabine and PemetrexedAlthough no overall differences in survival have been observed betweenthe many chemotherapy combinations in non–small-cell lungcancer, the clinical application of mRNA expression levels of amplifiedgenes may disclose many genetic influences on cytotoxic drug sensitivityand enable clinicians to tailor chemotherapy according to eachindividual’s gene profile. Specifically, the assessment of ribonucleotidereductase subunit M1 and thymidylate synthase mRNA expression levelsmight select patients who benefit from gemcitabine (Gemzar) orpemetrexed (Alimta) combinations. Until recently, clinical prognosticfactors such as performance status, weight loss, and lactate dehydrogenasewere the only parameters used to predict chemotherapy responseand survival. However, accumulated data indicate that overexpressionof genes involved in cancer glycolysis pathways plays an important role,and might be an independent mechanism of chemoresistance. Thedysregulation of glycolytic genes is affected by growth signals involvingthe PI3K/Akt pathway and downstream genes such as hypoxiainduciblefactor-1-alpha. One can thus envision that substantial improvementsin therapeutic outcome could benefit from the integrationof tailored ribonucleotide reductase-dependent chemotherapy, ribonucleotidereductase antisense therapy, and targeted therapy.
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Paraneoplastic Leukocytosis: An Unusual Manifestation of Squamous Cell Carcinoma of the Urinary BladderA 76-year-old woman with a history of dementia, hypertension, type 2 diabetes mellitus, and newly diagnosed squamous cell carcinoma of the urinary bladder was referred to Indiana University Medical Center after 3 to 4 weeks of hospitalization at two other hospitals.
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Breast Cancer Following Radiation for Hodgkin Lymphoma: Clinical Scenarios and Risk-Reducing StrategiesWe review available strategies for screening and risk reduction through chemoprevention or risk-reducing surgery, as well as challenges for management of breast cancer in patients with prior exposure to radiation for Hodgkin lymphoma.
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The Promise of Pharmacogenomics: Gemcitabine and PemetrexedAlthough no overall differences in survival have been observed betweenthe many chemotherapy combinations in non–small-cell lungcancer, the clinical application of mRNA expression levels of amplifiedgenes may disclose many genetic influences on cytotoxic drug sensitivityand enable clinicians to tailor chemotherapy according to eachindividual’s gene profile. Specifically, the assessment of ribonucleotidereductase subunit M1 and thymidylate synthase mRNA expression levelsmight select patients who benefit from gemcitabine (Gemzar) orpemetrexed (Alimta) combinations. Until recently, clinical prognosticfactors such as performance status, weight loss, and lactate dehydrogenasewere the only parameters used to predict chemotherapy responseand survival. However, accumulated data indicate that overexpressionof genes involved in cancer glycolysis pathways plays an important role,and might be an independent mechanism of chemoresistance. Thedysregulation of glycolytic genes is affected by growth signals involvingthe PI3K/Akt pathway and downstream genes such as hypoxiainduciblefactor-1-alpha. One can thus envision that substantial improvementsin therapeutic outcome could benefit from the integrationof tailored ribonucleotide reductase-dependent chemotherapy, ribonucleotidereductase antisense therapy, and targeted therapy.
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Triple-Negative Breast Cancer: Not Entirely NegativeTriple-negative breast cancer (TNBC) remains a very challenging entity today, but with the identification of new targets and further optimization of therapy, the landscape for TNBC may not look so negative. In the future, “TNBC” may be considered an antiquated misnomer, as we will have identified various breast cancer subgroups based on what they “are” rather than what they “are not.”
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Genomic Testing in Colorectal Cancer: How Much Is Enough?The identification and characterization of gene signatures, driver events, and pharmacogenomics in molecularly homogeneous subsets of patients is likely to advance effective drug development strategies in colorectal cancer.
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Further Perspectives on Treating Localized Prostate CancerStandard treatment options for prostate cancer patients include surveillance, surgery, external-beam radiotherapy, brachytherapy, the combination of external-beam and brachytherapy, and the combination of radiotheraputic modalities with hormonal therapy, for appropriately chosen patients.
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Gene Therapy for Head and Neck CancersDespite advances in surgery, radiotherapy, and chemotherapy, survival of patients with squamous cell carcinoma of the head and neck has not significantly improved over the past 30 years. Locally recurrent or refractory disease is particularly difficult to treat. Repeat surgical resection and/or radiotherapy are often not possible, and long-term results for salvage chemotherapy are poor. Recent advances in gene therapy have been applied to recurrent squamous cell carcinoma of the head and neck. Many of these techniques are now in clinical trials and have shown some efficacy. This article discusses the techniques employed in gene therapy and summarizes the ongoing protocols that are currently being evaluated in clinical trials. [ONCOLOGY 15(3):303-314, 2001]
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Management of Hot Flushes Due to Endocrine Therapy for Prostate CarcinomaEndocrine manipulation plays a crucial role in the treatment of advanced prostate carcinoma. Recent enthusiasm for earlier use of endocrine therapy has increased the significance of diminishing treatment-related side effects,
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Gene Expression Assays in Early-Stage Breast CancerDr. Sparano discusses the implications of TAILORx, the first trial to use Oncotype DX in clinical decision making.
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New SSRI Antidepressants Offer Advantages in Cancer PatientsA 43-year-old married man was referred to Memorial Sloan-Kettering Cancer Center in June, 1995, for further management of a malignant brain tumor. He was asymptomatic until April, 1994, when he suffered a generalized seizure and was admitted to a local hospital. An MRI revealed a right parietal lobe lesion. The tumor was resected and found to be a glioblastoma multiforme.
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Graft Purging in Autologous Bone Marrow Transplantation: A Promise Not Quite FulfilledClonogenic tumor cells contained within hematopoietic stem cell(HPC) grafts may contribute to relapse following autologous transplantation.Graft purging involves either in vivo or ex vivo HPC manipulationin order to reduce the level of tumor cell contamination.Some phase II trials suggest that patients who receive purged productsmay have a superior transplant outcome. Phase I trials demonstratethe feasibility of purging methods including ex vivo graft incubationwith chemotherapeutic drugs, monoclonal antibodies and complement,and CD34+ cell selection. A phase II trial in follicular non-Hodgkin’slymphoma demonstrates that patients who receive HPC products purgednegative for bcl-2 gene rearrangements have a superior outcome, comparedwith patients who receive polymerase chain reaction (PCR)-positiveproducts. This finding, however, has not been confirmed in a randomizedtrial. HPC purging has demonstrated no benefit in a phase IIItrial in myeloma. Phase II trials in acute myelogenous leukemia showcomparable outcomes for patients who receive either purged orunpurged HPC grafts. Limitations of purging include possible progenitorcell loss, delayed engraftment, and qualitative immune defects followingtransplant. Data to justify routine use of HPC graft purging areinsufficient. Phase I and II data support development of phase III trialsof both in vivo and in vitro purging methods.
