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Cancer Metabolism as a Therapeutic TargetOngoing studies are attempting to understand the reasons that tumor cells engage in aerobic glycolysis in lieu of oxidative phosphorylation. In this review, we discuss known benefits to tumor cells from this metabolic switch, and we highlight key enzymes that play a role in aerobic glycolysis. We also describe novel therapeutic options targeting glucose metabolism.
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Clinical Management of EGFRI Dermatologic Toxicities: The Japanese PerspectiveEpidermal growth factor receptor inhibitors (EGFRIs) have demonstrated clinical activity in patients with non–small-cell lung cancer, pancreatic cancer, and colorectal cancer. EGFRIs are generally well tolerated, but reversible dermatologic toxicities are commonly associated with their use. Limited clinical evidence has characterized these adverse reactions as a class effect. For panitumumab (Vectibix), mild-to-moderate dermatologic toxicities are the most common associated adverse reactions. This report details the Japanese experience in the management of dermatologic toxicities associated with panitumumab use. Treatment selection for skin toxicity in Japan is also detailed, with a flowchart depicting strategies to treat various stages of dermatologic toxicities. Panitumumab was well tolerated in Japanese patients with advanced solid tumors, with a safety profile similar to that seen in non-Japanese patients.
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POINT: Is There Still a Role for Intraperitoneal Platinum Therapy in Ovarian Cancer?Intraperitoneal (IP) chemotherapy is a reasonable treatment approach for ovarian cancer because it can directly expose the surface tissues to which the cancer has disseminated to an extremely high concentration of the chemotherapy drug.
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Minimizing Morbidity in Melanoma SurgeryHere we review some of the most significant changes in the surgical management of melanoma that have reduced morbidity and thereby improved patient outcomes.
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The Emerging Role of HE4 in the Evaluation of Epithelial Ovarian and Endometrial CarcinomasIn this review, we discuss the discovery and biologic significance of HE4 and evaluate available evidence regarding the utility of HE4 as a biomarker for ovarian and endometrial cancer.
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Book Review: Tamoxifen: A Guide for Clinicians and PatientsIt is unusual to find an entire book dedicated to one therapeutic agent because a balanced, comprehensive analysis generally requires a somewhat broader perspective, particularly if it is targeted not only to the physicians treating a particular disease
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Gemcitabine and Irinotecan in Locally Advanced or Metastatic Biliary Cancer: Preliminary ReportChemotherapy has had limited success in biliary tract cancer. Of thenewer agents, gemcitabine (Gemzar) and irinotecan (CPT-11, Camptosar)both have single-agent activity in patients with advanced disease.We conducted a phase II trial to study the efficacy and toxicity of thecombination of gemcitabine plus irinotecan in patients with locallyadvanced or metastatic biliary tract cancer. The study has enrolled 14patients with histologically or cytologically documented cancer of thebiliary tract or gallbladder with bidimensionally measurable disease,Eastern Cooperative Oncology Group performance status 0 or 1,decompressed biliary tree, and no prior exposure to chemotherapy.Gemcitabine at 1,000 mg/m2 and irinotecan at 100 mg/m2 were bothadministered on days 1 and 8, every 21 days. In patients who had lessthan grade 3 hematologic and less than grade 2 nonhematologic toxicityfollowing cycle 1, the dose of irinotecan was increased to 115 mg/m2 forsubsequent cycles. A total of 65 cycles of chemotherapy have beenadministered, with an average of 4.5 cycles per patient (range: 1 to 11cycles). The median treatment duration was 3 months (range: 0.75 to 8months). An objective partial response was determined radiographicallyin two patients (14%) while stable disease for periods ranging from 4to 11.5 months was noted in six patients (43%). Toxicity consisted ofgrade 3/4 neutropenia in seven patients (50%) with no episodes offebrile neutropenia, grade 3/4 thrombocytopenia in four (28%), grade3 diarrhea in two (14%), and grade 3 nausea in one patient. Thecombination of gemcitabine plus irinotecan appears to possess modestclinical activity, and it is well tolerated in patients with advanced biliarycancer. Patient accrual is ongoing to this study.
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Cancer Management Chapter 20: Melanoma and other skin cancersSkin cancer is the single most common form of cancer, accounting for more than 75% of all cancer diagnoses. More than 1 million cases of squamous cell and basal cell carcinomas are diagnosed annually, with a lifetime risk of more than one in five. The vast majority of skin cancers can be cured with surgery alone. Resection is the mainstay of therapy, even for skin cancer involving regional lymph nodes or, in some cases, more distant metastatic sites.
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Toward a Breast Cancer Vaccine:Work in ProgressIn the current issue of ONCOLOGY,Drs. Emens and Jaffee haveprovided an excellent overview ofthe basic mechanisms involved in thetumor-specific immune response, aswell as a comprehensive update ofresearch on immune-based therapiesfor breast cancer.
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Neoadjuvant Combined-Modality Therapy for Locally Advanced Rectal Cancer and Its Future DirectionHere we discuss the evolution of standard therapy for rectal cancer patients and the use of preoperative CRT for the treatment of locally advanced disease. Treatment schemes that have attempted to broaden the horizons of standard therapy include the use of induction chemotherapy and “watch-and-wait” approaches.
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Commentary (Moore): Prechemotherapy Assessment of Neutropenic RiskChemotherapy-induced febrile neutropenia (FN) predisposes patients to life-threatening infections and typically requires hospitalization. The goal was to investigate whether a risk assessment tool aligned with national guidelines could help identify patients at risk of FN and reduce FN-related hospitalizations. Beginning in October 2004, oncology nurses applied the new risk assessment tool to all patients initiating chemotherapy or a new regimen. Patients at risk for FN received prophylactic colony-stimulating factor. Charts for 189 patients receiving chemotherapy in fiscal year 2005 (FY05) were compared with charts of 155 patients receiving chemotherapy in FY04, before the tool was implemented. The incidence of FN-related hospitalization declined by 78%, from 9.7% in FY04 to 2.1% in FY05 (P = .003). Total hospital days decreased from 117 to 24. Routine systematic evaluation by oncology nurses improves recognition of patients at risk of FN and substantially reduces FN-related hospitalization.
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Psychological Complications of Prostate CancerThe authors challenge the notion that men with prostate cancer exhibit little psychological difficulty. In fact, we do not know much about actual distress rates in men with prostate cancer because few studies have directly measured distress in this population. Likewise, we do not know if the distress experienced by prostate cancer patients is qualitatively different from that of other cancer patients. By assuming that all men with prostate cancer "do well," we, as clinicians and researchers, may fail to ask patients important questions.
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Axillary Surgery After Chemotherapy: Challenges and OpportunitiesWhile breast-conserving surgery after neoadjuvant chemotherapy has become more accepted over time, methods of management of the axillary lymph nodes have remained matters of controversy.
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A Contemporary Review of HPV and Penile CancerThis article provides a comprehensive and up-to-date review of the role of HPV infections in men and in the development of penile cancer.
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An Argument for Aggressive Resection in MelanomaAny minimization of therapy in the name of reducing morbidity requires careful consideration. Reducing morbidity in melanoma is certainly a laudable goal, but locoregional disease control and cure must remain our primary objectives.
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Candidacy for Sorafenib in HCC Patients: Is There a Slippery SlopeIn North America, hepatocellular carcinoma (HCC) is one of only a few malignancies with an increasing incidence in recent years.[1]
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Non-Small-Cell Lung CancerThis management guide for non–small-cell lung cancer (NSCLC) covers the symptoms, screening, diagnosis, staging, and treatment of adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma of the lung.
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Adjuvant Therapy for Gastric Carcinoma: Closing out the CenturyGastric cancer is often advanced and unresectable at diagnosis. Even when a curative resection is possible, the 5-year survival rate for patients with T2 or higher tumors is less than 50%. Survival rates are even lower if lymph node metastases are present at surgery. Many phase III trials of adjuvant therapy have been conducted around the world during the past 4 decades, but their interpretation varies in the East and West. In the West, postoperative treatment modalities have not proven to be superior to postsurgical observation alone. Thus, at present, the routine use of postoperative therapy should be discouraged. In the Orient, however, routine use of postoperative chemotherapy and/or immunotherapy is common after a surgical procedure. Further investigations that correlate treatment response with molecular markers are needed. Improved clinical trial designs, including better preoperative staging, standardized surgical techniques, inclusion of adequate numbers of patients, and the continued use of a surgery-alone control group, are essential. In addition, the incorporation of newer active agents, radiotherapy, and new strategies, such as preoperative therapy and selection of patients based on tumor biology, would result in much-needed advances. Less toxic approaches with novel mechanisms of action, such as antiangiogenesis therapy, tumor vaccines, monoclonal antibodies, and matrix metalloproteinase inhibitors, also hold promise. [ONCOLOGY 13(11):1485-1494, 1999]
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What Is the Optimal Therapy for Childhood AML?The past 30 years have seen tremendous advances in the treatment of pediatric leukemia. What was once an invariably fatal diagnosis is now quite curable in close to 80% of cases. Unfortunately for children with acute myelogenous leukemia (AML), most of these developments have been in the treatment of acute lymphoblastic leukemia (ALL); even today, nearly half of all children diagnosed with AML will die of the disease.
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Chemotherapy for Brain TumorsTraditionally, cytotoxic drugs have played a limited role in the treatment of brain tumors, but important advances in chemotherapy have occurred during the past decade. Certain central nervous system (CNS) malignancies are
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UFT Plus Leucovorin for Metastatic Colorectal Cancer: Japanese ExperienceIn the United States and Europe, the combination of oral UFT plus leucovorin has been reported to produce objective responses and survival rates similar to those achieved with standard intravenous 5-fluorouracil plus leucovorin in patients with metastatic colorectal cancer, with reduced toxicity.
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Current Clinical Trials of R115777 (Zarnestra)R115777 (Zarnestra) is an orally available methylquinolone derivative from Johnson & Johnson Pharmaceutical Research and Development L.L.C. that is a potent and selective nonpeptidomimetic farnesyltransferase inhibitor (FTI).[1] FTIs represent a new class of agents that were originally developed to inhibit tumors by interfering with posttranslational processing of oncogenic Ras protein. The anticancer activity of FTIs might stem from their ability to effect various proteins other than Ras that can also mediate signal transduction, apoptosis, angiogenesis, and growth.[2]
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New Therapeutic Options for Chronic Lymphocytic LeukemiaFor decades, initial therapy for chronic lymphocytic leukemia (CLL) consisted of alkylators such as chlorambucil (Leukeran). The introduction of nucleoside analogs such as fludarabine and monoclonal antibodies such as rituximab (Rituxan) markedly changed the initial therapy of CLL, particularly in the United States. Fludarabine and combination regimens such as fludarabine/cyclophosphamide (FC) have achieved higher complete response (CR) rates and progression-free survival (PFS) than chlorambucil in previously untreated CLL, but long-term overall survival has not improved, due to concurrent improvement in salvage therapy of relapsed CLL patients. Upfront chemoimmunotherapy regimens such as fludarabine/rituximab (FR) and fludarabine/cyclophosphamide/rituximab (FCR) have similarly improved CR rates and PFS in previously untreated CLL patients, but it is unclear whether overall survival is improved. Advances in cytogenetic analysis and other biologic prognostic factors have greatly enhanced clinicians' ability to risk-stratify newly diagnosed CLL patients, and knowledge of such prognostic factors is necessary to properly interpret results of clinical treatment studies. The choice of initial therapy for an individual patient should depend upon the patient's age and medical condition, cytogenetic and other prognostic factors, and whether the goal of therapy is maximization of CR and PFS or palliation of symptoms with minimal toxicity.
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Gleason 6 Cancer Is Still CancerAs long as there is any risk of progression, G6 cancer cannot be equated to just a precursor lesion, and the emphasis should remain on screening patients with serum PSA measurement, contrary to the recommendation of the US Preventive Services Task Force.
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Choices in the Treatment of Cutaneous T-Cell LymphomaMycosis fungoides is responsive to treatment in the early stages; patients have a long duration of survival but are rarely cured of the disease. Therefore, patients require long-term, sequential therapies with as little toxicity as possible. In the early stages, skin-directed therapies, such as psoralen plus ultraviolet A in combination with retinoids or interferon, generally produce good, long-term responses. Once the disease progresses, systemic agents such as cytokines and retinoids are introduced. The cytokines provide a rational treatment approach for cutaneous T-cell lymphoma (CTCL) and produce good, long-lasting responses with few immunosuppressant effects. Denileukin diftitox (Ontak) has also been shown to produce good treatment effects, and its toxic effects can usually be controlled using prophylactic therapies. The synthetic retinoid bexarotene (Targretin) is taken orally and produces high response rates in CTCL, with a good long-term tolerability profile. Conventional systemic chemotherapies produce rapid responses and high response rates in CTCL, but these are generally of short duration and accompanied by myelosuppression and immunosuppression. Current treatment strategies therefore consist of the use of initial skin-directed therapies, with the addition of low-toxicity systemic biologic agents as the disease progresses; patients who do not respond to biologic agents should then receive conventional chemotherapies, starting with single agents and progressing to combination therapies.
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GM-CSF and Low-Dose Cytosine Arabinoside in High-Risk, Elderly Patients With AML or MDSPriming of leukemic cells with cytokines may enhance the efficacy of cell-cycle chemotherapy. In this study, we utilized these synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]), hydroxyurea, and low-dose cytosine arabinoside to treat elderly patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In a single-institution, retrospective study, we evaluated 94 treatments with concomitant hydroxyurea, cytosine arabinoside, and GM-CSF between the years of 1997 and 2003 in high-risk elderly patients with AML or MDS. A total of 80% of patients received all of the GM-CSF doses; 78% of patients received all of the cytosine arabinoside doses. Adverse events were minimal. No patient developed mucositis or alopecia. The most common adverse event was neutropenic fever, which was noted in 57% of patients. Twenty-one percent of patients remained neutropenic after treatment until death or relapse. Sixty-eight percent of patients reached an absolute neutrophil count of greater than 1,000 μL in a median of 33.5 days. Our data show an overall response rate of 52%, with a complete response rate of 39% and a partial response rate of 13%. Overall, our study showed that low-dose cytosine arabinoside given by continuous infusion together with continuous infusion GM-CSF and hydroxyurea was well-tolerated and effective in treating elderly AML and MDS patients who were not eligible for standard induction therapy.
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ACR Appropriateness Criteria® Recurrent Hodgkin LymphomaBy combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the complex decision-making associated with the management of recurrent Hodgkin lymphoma.
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Changing the ParadigmONCOLOGY recently sat down with Kenneth C. Anderson, MD, to discuss the current trends in multiple myeloma treatment, and the explosion of novel therapies that are paving the way to better and more durable outcomes and allowing patients to live longer and more meaningful lives.
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Plastic Surgery: A Component in the Comprehensive Care of Cancer PatientsThis article underscores what I believe is an important concept in the current state of the art of cancer therapy-namely that reconstructive plastic surgery is a key component in the treatment of many cancer patients. Clearly, the treatment of advanced-stage malignancies is now interdisciplinary, multimodal, and comprehensive. Chemotherapy and radiation therapy are becoming increasingly complementary modalities in the treatment of patients with more advanced disease.
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ACR Appropriateness Criteria® Nonsurgical Treatment for Locally Advanced Non–Small-Cell Lung Cancer: Good Performance Status/Definitive IntentThe treatment of inoperable stage III non–small-cell lung cancer (NSCLC) remains a challenge due to high rates of distant metastasis, local recurrence, and toxicity associated with definitive therapy.
