The Hippocratic principle of not harming the patient has remained up to this day an undisputed dogma in medicine. It reminds the physician of the possible detrimental, if not lethal, outcome of the treatment he prescribes and implicitly enforces good medical practice, although the true impact will unlikely be known. Oncology is one subspecialty of Medicine where this dilemma-ie, the pros and cons of treatment-is continuously put to the test, as the physician must decide on treatment for an often life-threatening illness while taking into account individual factors such as the patient’s will, performance status, available standard treatment options, and possible experimental approaches.
In this issue of ONCOLOGY, Dutcher, Mourad, and Ennis provide a current review of some newer strategies in the surgical and systemic treatment options for localized and advanced renal cell carcinoma (RCC).
Often, Congressional financing of programs can be secured only with indirect arguments. In the 1950s, the Eisenhower administration convinced Congress to fund the interstate highway system by claiming it was essential to enable Americans to evacuate cities in case of a nuclear attack by the Soviet Union. In the 1970s, advocates trying to persuade Congress to pay for dialysis argued that the procedure would be inexpensive, and that people would return to work and pay for themselves. Similarly, in the early 1980s, proponents of hospice advocated Medicare coverage because it was cheaper and better care for the dying.
In this article, we review the data surrounding the use of chemotherapy (CT) and chemoradiotherapy (CRT) in patients with resectable pancreatic cancer.
Management of ductal carcinoma in situ (DCIS) commonly involves excision, radiotherapy, and hormonal therapy. Radiotherapy is employed for local control in breast conservation. Evidence is evolving for several radiotherapy techniques exist beyond standard whole-breast irradiation.
In this article, we provide an overview of the currently available systemic agents, including immunotherapeutic agents and targeted tyrosine kinase inhibitors. We also provide a practical management algorithm to guide the practicing oncologist in the use of both of these new therapies and the more traditional local treatments.
Gastric cancer is a global health issue. Most cases are diagnosed atan advanced stage with poor prognosis. Current therapies have a modestimpact on survival. Surgery remains the only potentially curativetreatment, but is associated with a high rate of locoregional recurrenceand distant metastases. Total gastrectomy for proximal cancers is complicatedby postoperative morbidity and quality-of-life impairment.Combined-modality therapy may improve outcomes in this disease.Adjuvant therapy for gastric cancer has now become the standard inthe Western world. However, adjuvant therapy improves survival by onlya few months and is associated with high morbidity. Neoadjuvant therapyis commonly used for esophageal and gastroesophageal junction cancers,but is still regarded as investigational in gastric cancer. Severalsmall phase II studies indicate the feasibility of neoadjuvant strategies.The incorporation of novel, targeted agents into neoadjuvant programsand an assessment of biologic changes within the tumor may refinetherapy. This article provides a concise review of the literature onneoadjuvant therapy for gastric cancer and suggests avenues for furtherinvestigation.
Between 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
Two studies were carried out to determine the activity and evaluate the toxicity of oral chemotherapy with uracil and tegafur in a 4:1 molar ratio (UFT) plus or minus calcium folinate in elderly patients with advanced colorectal
Gastric cancer is the most chemosensitive adenocarcinoma among digestive neoplasms. A few years ago, we performed a phase II trial with the FLEP regimen, in which fluorouracil (5-FU) and leucovorin are combined
Erlotinib (Tarceva) is an orally available selective small-moleculeinhibitor of HER1/EGFR tyrosine kinase with a 50% inhibitory concentrationof 2 nM for purified tyrosine kinase. This agent has beenshown to produce stasis or regression of tumor growth in human cancerxenograft models, including non-small-cell lung cancer models.Ongoing preclinical investigations indicate that inhibition of the MAPKand Atk signaling pathways downstream of HER1/EGFR may be requiredfor optimal antitumor effects. Erlotinib exhibits inhibition ofMAPK and Atk kinases at concentrations higher than those requiredfor HER1/EGFR tyrosine kinase inhibition; such findings suggest thatmaximal inhibition of HER1/EGFR, requiring high erlotinib doses, isnecessary for optimum antitumor activity. These considerations aresupported by tumor models, including non-small-cell lung cancermodels, showing dose-related antitumor effects up to high doses oferlotinib. Erlotinib exhibits additive antitumor effects when combinedwith chemotherapeutic agents (cisplatin, doxorubicin, paclitaxel,gemcitabine [Gemzar], and capecitabine [Xeloda]), radiation therapy,and other targeted agents (eg, bevacizumab [Avastin]). Recent studiesindicate that erlotinib inhibits the EGFRvIII mutant at concentrationshigher than those required for inhibition of wild-type receptor. Ongoinginvestigation will help to determine optimal dosing and dose frequencyof erlotinib in various cancers in the clinical setting.
In spite of the complicated etiologic, clinical, and pathologic scenario of cryoglobulinemia, physicians can play a key role in its successful management by early recognition of the most common clinical presentations.
Coenzyme Q10, or CoQ10, is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier involved in the mitochondrial respiratory chain. In mitochondria, CoQ10 functions as a coenzyme that assists in the oxidative phosphorylation of nutrients, leading to production of cellular adenosine triphosphate (ATP), or energy.
I am a urologist in southwest Florida. As I discussed with one of our radiation oncologists (we use 21st Century Oncology), there are no trials comparing proton and standard radiation, eg, IMRT. If such a trial were conducted, I suspect, at best, the cancer control rates would be equivalent, and the side effect profiles would also be similar. So what is all the fuss?
Drs. Crawford and Hou provide an important clinical introduction to a novel class of hormonal agents that have been under development for several decades for the treatment of advanced and metastatic prostate cancer.
Head and neck melanoma is a rare and aggressive childhoodmalignancy. Surgery remains the primary treatment, with lymphaticinvolvement determined by neck dissection. In the adult population,sentinel lymph node biopsy has emerged as a less morbid yet accuratemethod of staging regional lymph nodes. This innovative technique canalso be used in the pediatric population.
Meningiomas are the most common primary brain tumor and comprise nearly one-third of all newly diagnosed primary brain tumors.
Upfront surgery allows for greater freedom to use all secondary treatment options for local and distant control, including adjuvant radiotherapy and ADT, thereby hopefully obviating the significant adverse quality-of-life sequelae from salvage surgery and brachytherapy for local relapse.
Drs. Pennington and Leffellhave provided an excellentoverview of the current uses ofMohs micrographic surgery. The procedurehas certainly come a long waysince the days of Frederic Mohs andthe application of zinc chloride paste(chemosurgery). Despite the fact that ithas indeed become the “gold standard”for the removal of basal cell carcinoma(BCC) and squamous cell carcinoma(SCC), there remain areas of controversyfor its use in melanoma and otherless common cutaneous neoplasms. Asmore dermatologists (and even a fewnondermatologists) have becometrained and gain experience in this specializedprocedure, and as more communitiesand university teaching centershave established growing Mohs practices,the procedure has become recognizedand embraced by health-careprofessionals and patients alike.
Von Roenn and Knopf provide a balanced review of the pathophysiology and treatment options for anorexia and cachexia associated with HIV and cancer. This is an important topic that cuts across subspecialty lines and typically frustrates clinicians. Fortunately, more has probably been learned about HIV-associated cachexia during the past decade than about cancer-associated cachexia during the previous three decades and a number of treatment options have emerged. The reader may therefore benefit from a summary of the practical implications of recent research on HIV-associated wasting. Several clinical guidelines can be recommended:
The use of live viruses for the treatment of cancer has been extensively studied in several preclinical and clinical models, as discussed in Nemunaitis’ thorough historical review of the subject.
In patients with an advanced disease or a terminal illness, it may become necessary to institute parenteral opioid therapy either on a temporary basis (for acute breakthrough pain) or permanently. Continuous intravenous or subcutaneous opioid infusions have been the mainstay of parenteral opioid therapy for oncologic pain. Patient-controlled analgesia (PCA) now offers an alternative modality, and Drs. Bruera and Ripamonti review the current status of this relatively new technique. Is there any evidence to suggest the superiority of one modality over the other for the treatment of oncologic pain?
Surgery is the only curative option for patients with colorectal cancer. The goal of other modalities, such as chemotherapy, immunotherapy, and radiotherapy, is to prolong survival and reduce the risk of recurrence.
Gemcitabine is a potent radiosensitizer in both laboratory studies and in the clinic. Initial laboratory studies showed that gemcitabine radiosensitizes a wide variety of rodent and human tumor cells in culture. Maximum
The 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
The introduction of the tyrosine kinase inhibitor imatinib mesylate (Gleevec) has profoundly changed the treatment paradigm for patients with chronic myelogenous leukemia (CML).
Question 1: Breast cancer remains among the most frequent diagnoses of cancer in women in the United States. Importantly research indicates that deaths due to breast cancer are decreasing, in part due to advances in treatment and earlier detection. Could you please comment about the advances in breast cancer imaging that have helped to facilitate earlier detection?Question 2: Could you briefly comment on the role of each of these modalities used in breast imaging?A. X-Ray mammography (digital and film screen)B. UltrasoundC. Molecular imagingD. Breast-specific gamma imagingQuestion 3: Could you please discuss indications for breast-specific gamma imaging and the clinical data to support these indications?Question 4: Are you able to cite an example as to how you used breast-specific gamma imaging in the clinic?Question 5: Could you please discuss the role of imaging in staging and treating breast cancer most appropriately? Is there new or novel technology that oncologists should be aware of when imaging is used for optimal visualization to assist in staging a woman diagnosed with breast cancer?Question 6: In your own clinical experience, what advances have you witnessed in breast imaging, particularly in regard to breast cancer, over the past 5 years?Question 7: Do you have any final comments you would like to make to our audience about advances or trends in breast imaging as it pertains to women with breast cancer?
Emerging therapies in the management of ovarian cancer have resulted in a shift in paradigm, including in the appropriate time to institute therapy, and in the selection of therapy. This review focuses on chemotherapy and emerging biologic agents that present a therapeutic option for patients with recurrent ovarian cancer.
Biliary tract drainage, with or without placement of an endoprosthesis, is used as a palliative therapy for malignant biliary obstruction. The first truly internal endoprostheses represented a distinct improvement over internal-external catheters but still remained patent for only 4 to 6 months. Metallic stents have a long-term patency of 6 to 8 months. At present, it appears that patients with unresectable pancreatic cancer should be palliated with endoscopically placed plastic or metal stents, whereas those with malignant obstructions higher in the biliary tree are probably better managed with transhepatically placed stents. The combination of brachytherapy plus external-beam radiation followed by implantation of a Gianturco metal stent may be a viable approach to treating obstructions in patients with cholangiocarcinoma. For those with other noncholangiocarcinomas, particularly when life expectancy exceeds anticipated stent patency duration, the Wallstent may be the device of choice. [ONCOLOGY 9(6):493-504, 1995]
Multiple myeloma is now the most common indication for autologous stem cell transplantation (ASCT) in North America, with over 5,000 transplants performed yearly (Center for International Blood and Marrow Transplant Research [CIBMTR] data). While the role of ASCT as initial therapy in multiple myeloma has been established by randomized studies, newer therapies are challenging the traditional paradigm. The availability of novel induction agents and newer risk stratification tools, and the increasing recognition of durability of remissions are changing the treatment paradigm. However, even with arduous therapy designed to produce more complete remissions—for example, tandem autologous transplants—we have seen no plateau in survival curves. A tandem autologous procedure followed by maintenance therapy may be performed in an attempt to sustain remission. Sequential autologous transplants followed by nonmyeloablative allotransplants are pursued with the hope of "curing" multiple myeloma. We examine how the key challenges of increasing the response rates and maintaining responses are being addressed using more effective induction and/or consolidation treatments and the need for maintenance therapies after ASCT. We argue that given the biologic heterogeneity of multiple myeloma, risk-adapted transplant approaches are warranted. While the role of curative-intent, dose-intense toxic therapy is still controversial, conventional myeloablative allogeneic transplants need to be reexamined as an option in high-risk aggressive myeloma, given improvements in supportive care and transplant-related mortality.