scout

Authors

Latest Article

From Radiotherapy to Targeted Therapy: 20 Years in the Management of Non-Small-Cell Lung Cancer

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Before 1980, radiotherapy was considered the only real recourse in advanced disease. In 1995, a landmark meta-analysis of trials conducted in the 1980s and early 1990s demonstrated a survival benefit with platinum-based chemotherapy. Newer chemotherapy agents and improved supportive care measures have allowed more patients to benefit from chemotherapy with reduced toxicity. Concurrent platinum-based chemotherapy and radiotherapy has improved the survival in stage III disease, and recently chemotherapy has also demonstrated improved survival in resected early-stage disease. The majority of patients still present with advanced unresec disease for whom the prognosis remains poor, but for key subpopulations the outlook has improved markedly since the emergence of targeted therapies directed against the epidermal growth factor receptor and vascular endothelial growth factor receptor pathways. Patient selection and the incorporation of targeted therapies with cytotoxic chemotherapy are the focus of many ongoing studies, and there is an abundance of new agents undergoing clinical trials. Together, these developments have moved us away from the nihilism of 20 years ago into an era of unprecedented optimism in taking on the many remaining challenges of managing NSCLC in the 21st century.

Latest Article

Tandem Transplantation in Multiple Myeloma

The use of high-dose chemotherapy and autologous stem cellsupport in the past decade has changed the outlook for patients withmultiple myeloma. In newly diagnosed patients, complete remissionrates of 25% to 50% can be achieved, with median disease-free andoverall survivals exceeding 3 and 5 years, respectively. Despite theseresults, autologous transplantation has not changed the ultimatelyfatal outcome of the disease, as there is no substantial evidence of“cure” in most published studies. An additional high-dose chemotherapycourse (with tandem transplants) appears to improve progressionfreesurvival, although the effect is not discernible until 3 to 5 yearsposttransplant. The recent reports of tandem autologous transplant formaximum cytoreduction followed by nonmyeloablative allogeneictransplant for eradication of minimal residual disease appears promisingand deserve further investigation. A central issue of tandemtransplants, whether they involve autologous or allogeneic transplants,revolves around defining the subsets of patients who will benefitfrom the procedure. Good-risk patients (defined by normal cytogeneticsand low beta-2–microglobulin levels), especially those who achievea complete or near-complete response after the first transplant, appearto benefit the most from a second cycle. High-risk patients (defined bychromosomal abnormalities usually involving chromosomes 11 and 13and high beta-2–microglobulin levels) whose median survival aftertandem transplant is less than 2 years should be offered novel therapeuticinterventions such as tandem “auto/allo” transplants. Until theefficacy and safety of this procedure is fully established, it should belimited to high-risk patients.

Latest Article

Gemcitabine in Combination With Trastuzumab and/or Platinum Salts in Breast Cancer Cells With HER2 Overexpression

Trastuzumab (Herceptin) is an effective treatment in patients withHER2-overexpressing metastatic breast cancer. Risk of trastuzumabinducedcardiotoxicity raises concerns regarding combined use withanthracyclines or other potentially cardiotoxic agents followinganthracycline treatment. We characterized interactions betweentrastuzumab and gemcitabine (Gemzar) and the combination ofgemcitabine and cisplatin or carboplatin (Paraplatin) as such combinationsmight help reduce the risk of cardiotoxicity. Multiple drugeffect/combination index isobologram analysis was used to study theefficacy of chemotherapeutic drug plus trastuzumab combinations inHER2-overexpressing breast cancer cell lines. Combination index valueswere derived from parameters of the median effect plots, and statisticaltests were used to determine whether the mean combinationindex at multiple effect levels significantly differed from a combinationindex value of 1.0 (values < 1.0 indicate synergy; values > 1.0,antagonism; values equal to 1.0, additivity). At a wide range of clinicallyachievable drug concentrations, interactions between trastuzumaband gemcitabine were synergistic at low concentrations of gemcitabineand antagonistic at high concentrations. A consistent synergistic interactionwas observed with the three-drug combination of trastuzumabplus gemcitabine plus carboplatin or cisplatin. Available clinical dataon the use of trastuzumab plus gemcitabine, and trastuzumab plusgemcitabine/paclitaxel, as well as clinical data on the use ofgemcitabine/cisplatin in breast cancer, are discussed. These findingsindicate that trastuzumab plus gemcitabine and trastuzumab plusgemcitabine plus cisplatin or carboplatin are rational combinations toevaluate in clinical trials.

Latest Article

Gemcitabine/Paclitaxel as First-Line Treatment of Advanced Breast Cancer

Gemcitabine (Gemzar) and paclitaxel exhibit good activity and goodsafety profiles when used alone and together in the treatment of advancedbreast cancer. In a phase II trial, 45 patients with metastaticbreast cancer received gemcitabine at 1,200 mg/m2 on days 1 and 8 andpaclitaxel at 175 mg/m2 on day 1 every 21 days. Twenty-seven patients(60.0%) had prior adjuvant therapy. Objective response was observedin 30 patients (objective response rate 66.7%, 95% confidence interval[CI] = 52%–71%), including complete response in 10 (22.2%) and partialresponse in 20 (44.4%). Median duration of response was 18 months(95% CI = 11–26.7 months), median time to tumor progression for theentire population was 11 months (95% CI = 7.1–18.7 months), medianoverall survival was 19 months (95% CI = 17.3–21.7 months), and the1-year survival rate was 69%. Treatment was well tolerated, with grade3/4 toxicities being infrequent. Grade 3/4 leukopenia, neutropenia, andthrombocytopenia were each observed in six patients (13.3%). No patientwas discontinued from the study due to hematologic ornonhematologic toxicity. Thus, the gemcitabine/paclitaxel combinationshows promising activity and tolerability when used as first-line treatmentin advanced disease. The combination recently has been shownto be superior to paclitaxel alone as first-line treatment in anthracyclinepretreatedadvanced disease according to interim results of a phase IIItrial and it should be further evaluated in comparative trials in breastcancer.