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The effective use of cancer chemotherapy requires a thorough understanding of the principles of neoplastic cell growth kinetics, basic pharmacologic mechanisms of drug action, pharmacokinetic and pharmacodynamic variability, and mechanisms of drug resistance. Recent scientific advances in the field of molecular oncology have led to the identification of large numbers of potential targets for novel anticancer therapies. This has resulted in a tremendous expansion of the drug development pipeline, and in the present era, the diversity of clinically useful novel anticancer therapeutic agents is growing at an unprecedented rate. However, the great enthusiasm that surrounds these new agents must be tempered by the challenges they present in optimizing their clinical use and in rationally integrating them with existing anticancer therapies. This discussion focuses on the basic principles underlying the development of modern combination chemotherapy, and it is followed by a description of the major classes of chemotherapeutic drugs and their mechanisms of action.

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Gavin Jones, MD, and colleagues explore the landscape of radiation therapy in diffuse large B-cell lymphoma.

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Gemcitabine (Gemzar) and irinotecan (CPT-11, Camptosar) are active cytotoxic drugs against pancreatic cancer. Preclinical data evaluating the combination of gemcitabine and irinotecan suggest dose-dependent synergistic

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Pemetrexed (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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If there is one disease for which patients have experienced a significant improvement in the cure rate over the past 10 years, it is diffuse large B-cell lymphoma (DLBCL).

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Since cancer is incurable in many patients, palliation of symptoms and quality-of-life issues are important aspects of therapy. Uracil and tegafur (UFT) plus calcium folinate are the components of the oral agent known

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Granulocyte-macrophage colony-stimulating factor (GM-CSF,sargramostim [Leukine]) is a powerful cytokine that is able to stimulatethe generation of dendritic cells. Adjuvant treatment with continuous lowdoseGM-CSF has been shown to prolong survival of stage III/IV melanomapatients. Data on continuous low-dose GM-CSF therapy in tumorsother than prostate cancer are still lacking.

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The use of chemotherapy in the treatment of early and advancednon–small-cell lung cancer (NSCLC) has increased during the pastdecade. One of the main reasons for the increased acceptance of chemotherapyis the development of several new cytotoxic agents with aunique mechanism(s) of action and high single-agent activity, combinedwith a favorable toxicity profile. Pemetrexed (Alimta) is a novelantifolate that inhibits several enzymes involved in DNA synthesis(thymidylate synthase [TS], dihydrofolate reductase [DHFR], andglycinamide ribonucleotide formyltransferase [GARFT]). Pemetrexed’stoxicity is markedly reduced by folic acid and vitamin B12 supplementation.The compound has been studied extensively in various tumor types,including NSCLC. In NSCLC, pemetrexed at 500 mg/m2, every 3 weeks,given IV over 10 minutes, has shown promising activity, and can safelybe administrated with vitamin supplementation. After registration,single-agent pemetrexed will certainly add to the chemotherapeuticoptions available for pretreated patients and will most likely changesignificantly chemotherapy prescriptions in second-line chemotherapy.In first-line chemotherapy, the role of platinum-based and -free combinationdoublet chemotherapy with pemetrexed still needs to be defined.Phase II data indicate high efficacy combined with favorabletoxicity for pemetrexed in combination with cisplatin, carboplatin(Paraplatin), oxaliplatin (Eloxatin), gemcitabine (Gemzar), andvinorelbine (Navelbine). This review summarizes the clinical experienceobtained thus far during the early clinical development ofpemetrexed in NSCLC.

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Surgical debulking of epithelial ovarian carcinoma has been a mainstay of therapy for more than 50 years-since the approach was first advocated by Meigs in 1934.[1] In 1968, Munnell[2] introduced the idea of the "maximum surgical effort”-essentially the removal of as much cancer as possible.

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Our phase II study results demonstrating high efficacy and low toxicity for a weekly schedule of high-dose, 24-hour infusional 5-fluorouracil(5-FU)/folinic acid (HD5-FU/FA) in intensively pretreated patients with metastatic

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Luteinizing hormone-releasing hormone analogs (LHRHa) are often used alone or in combination with tamoxifen to suppress ovarian function in premenopausal women with endocrine-responsive breast cancer. However, aromatase inhitiors (AIs) are now the preferred first-line endocrine treatment for postmenopausal women with breast cancer.

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CHICAGO-Targeted radiation of breast cancer after lumpectomy reduces treatment time from six and a half weeks to five days, while reducing pain and improving cosmetic outcome, according to a study presented at RSNA 2008 (abstract SSC19-02).

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Preliminary phase 2 trial data show durvalumab plus lenalidomide was superior to durvalumab alone in refractory/advanced cutaneous T-cell lymphoma.

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This feature examines the case of a patient with newly diagnosed breast cancer in the setting of a first-trimester pregnancy presenting to our multidisciplinary breast cancer clinic.

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Although testicular cancer is a rare disease accounting for only 1% of all male neoplasms, it represents a paradigm for cancer curability. Overall, more than 95% of patients can expect to be cured of their disease with minimal long-term toxicity. Given these expectations, it is critical that cancer care providers are familiar with the diagnostic and therapeutic challenges encountered in these rare patients. In particular, clinicians managing these patients should be aware of some of the pitfalls encountered when determining relapse. In a series of case presentations, we review the evaluation and management of patients with persistent elevation of serum tumor markers and postchemotherapy residual radiographic abnormalities.

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We 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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Spiegel and Moore provide an excellent review of the utility of psychological therapeutic techniques in cancer patients. These techniques are frequently viewed with alarm by the medical community because of unsubstantiated claims that they improve survival in cancer patients. Patients who expect such techniques as visual imagery to change the course of their illness may experience poorer psychological adjustment and needless guilt. However, it is a shame to "throw the baby out with the bath water." Psychological techniques have a significant role to play in the treatment of cancer patients.

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Cancer causes changes in the family's identity, roles, and daily functioning. Studies document that spouses are as distressed as cancer patients and that spousal and patient distress are correlated. Three major areas of caregiver

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Multiple randomized trials and their meta-analysis have demonstrated an overall survival benefit from postmastectomy radiotherapy in women with node-positive breast cancer. However, none of the patients treated in these trials received neoadjuvant chemotherapy, which is now an increasingly common approach.

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With regard to potential research strategies relevant to the treatment of triple-negative breast cancer/basal-like breast cancer, potential targets include PTEN, INPP4B, PIK3CA, KRAS, BRAF, EGFR, FGFR1, FGFR2, IGFR1, KIT, MET, PDGFRA, and the HIF1-α/ARNT pathway. Many of these will be discussed further in this review article.

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In this review, we focus on the testosterone/androgen receptor pathway that is being targeted with potent new agents; we also discuss other important alternative biologic pathways that have given rise to new therapeutics that may attenuate prostate cancer growth, survival, and propagation.

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Drs. Levine and Gemignani havecomposed an excellent comprehensivereview of the issuessurrounding prophylactic surgeryin patients at high risk for breast andovarian cancer. Their article focuseson the role of BRCA1/2 mutations inthe risk of developing hereditary breastand ovarian cancer and the data supportingrisk reduction in mutation carriersundergoing prophylactic surgery.

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Ibritumomab tiuxetan (Zevalin) consists of an anti-CD20 murine IgG1 kappa monoclonal antibody covalently bound to tiuxetan (MX-DTPA), which stably chelates yttrium-90 for therapy. Ibritumomab tiuxetan therapy involves pretreatment with

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Nursing management of patients with advanced malignancies presents a formidable challenge. In addition to the discomfort and debilitation these diseases can cause, side effects of traditional treatment modalities such as surgery, chemotherapy, and radiation may lead to severe and sometimes fatal sequelae. New targeted therapies promise an effective treatment with more easily tolerated and managed side effects. Basic understanding of the drugs' mechanism of action contributes to the successful management of the toxicities that can be manifested. Effective patient education results in improved compliance with treatment regimens and potentially improved clinical outcomes. Nursing intervention remains a vital component in the successful use of these novel agents.

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Including the entire course of care in the efforts to improve quality and contain costs will make the short-term implementation more complex and perhaps controversial. However it will reflect the way that contemporary oncology care is delivered, and will allow for holistic care management and an optimization of cost.

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Tanner et al provide a concise review of lung cancer screening, including discussion of past failed attempts, the success of the National Lung Screening Trial (NLST), and promising new avenues for improving on the NLST results.

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Drs. Takimoto and Allegra present a comprehensive overview of the development of antifolates over the past decade and a half. The antifolates are antimetabolite antineoplastic agents that are structurally and chemically similar to naturally occurring folates required for the synthesis of purines and pyrimidines. These drugs interfere with DNA synthesis by inhibiting key enzymes. They are transported across the plasma membrane and converted intracellularly to cytotoxic species, which must compete with endogenous substrates for target enzyme binding.