Showing papers in "Oncology in 1997"

HER2 overexpression and paclitaxel sensitivity in breast cancer: therapeutic implications.

Abstract: Overexpression 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 fluoruracil) 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.

The Prostate Cancer Intervention Versus Observation Trial (PIVOT)

Abstract: The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized trial designed to determine whether radical prostatectomy or expectant management provides superior length and quality of life for men with clinically localized prostate cancer. Conducted at Department of Veterans Affairs and National Cancer Institute medical centers, PIVOT will enroll over 1,000 individuals < 75 years of age. The primary study end point is all-cause mortality. Secondary outcomes include prostate cancer- and treatment-specific morbidity and mortality, health status, predictors of disease-specific outcomes, and cost-effectiveness. Within the first 3 years of enrollment, over 400 men have been randomized. Early analysis of participants' baseline characteristics indicate that enrollees are representative of men diagnosed with clinically localized prostate cancer throughout the United States. Therefore, results of PIVOT will be generalizable. These results are necessary in order to determine the preferred therapy for clinically localized prostate cancer.

The crisis of cancer: psychological impact on family caregivers

Abstract: 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 concern are: fear of cancer and its spread, helping patients deal with the emotional ramifications of the disease, and managing the disruptions caused by cancer. From 20% to 30% of partners suffer from psychological impairment and mood disturbance as a result of the spouse's cancer. Factors that may predict high levels of spousal distress include: disease stage; emotional adjustment of the patient; gender, age, and other characteristics of the spouse; marital adjustment; and family functioning. Studies show that interventions do not reduce spousal distress. Future studies should explore the role of mediating factors, such as coping style, marital adjustment, and family functioning, on the relationship between illness demands or prognosis and distress. Interventions could then be targeted to high-risk individuals.

Quality of Life Among Long-Term Cancer Survivors

Abstract: Thanks to advances in cancer diagnosis and treatment, there are now more than 10 million cancer survivors in the United States. Successful treatment of cancer has resulted in increased demands on survivors and has had diverse effects on the quality of life (QOL) of patients and their families. A model of QOL encompassing dimensions of physical, psychological, social, and spiritual well-being has been applied to illustrate the multidimensional needs of cancer survivors and the necessity of comprehensive care extending over the long term. Data from a recent survey of members of the National Coalition of Cancer Survivorship (NCCS) is presented, along with a summary of issues compiled by the NCCS that merit future attention. [ONCOLOGY 11(4):565-571, 1997]

Speech and Swallowing Rehabilitation for Head and Neck Cancer Patients

Abstract: Head and neck cancer and its treatment frequently cause changes in both speech and swallowing, which affect the patient's quality of life and ability to function in society. The exact nature and severity of the post-treatment changes depend on the location of the tumor, the choice of treatment, and the availability and use of speech and swallowing therapy during the first 3 months after treatment. This paper reviews the literature on speech and swallowing problems in various types of treated head and neck cancer patients. Effective swallowing rehabilitation depends on the inclusion of a video-fluorographic assessment of the patient's oropharyngeal swallow in the post-treatment evaluation. Pilot data support the use of range of motion (ROM) exercises for the jaw, tongue, lips, and larynx in the first 3 months after oral or oropharyngeal ablative surgical procedures, as patients who perform ROM exercises on a regular basis exhibit significantly greater improvement in global measures of both speech and swallowing, as compared with patients who do not do these exercises.

Expression of E-Cadherin, α-Catenin, β-Catenin and Plakoglobin in Esophageal Carcinomas and Its Prognostic Significance

Abstract: It has been suggested that inactivation of the cadherin-mediated cell-cell adhesion system plays a role in the initial steps of cancer invasion and metastasis. Expression of E-cadherin and its intracy

Persistence of lymphedema reduction after noninvasive complex lymphedema therapy

Abstract: We treated 119 consecutive patients with lymphedema with complex lymphedema therapy (CLT) Lymphedema reductions after CLT averaged 626% in the 56 patients with one affected arm and 686% in the 38 patients with one affected leg In the 23 patients with bilateral affected lower limbs, lymphedema volume decreased by 3,681 cm3 in the right leg and by 3,433 cm3 in the left leg Due to its small number, the group with bilateral affected arms was not analyzed After 36 months' follow-up, the average reduction increased to 638% in individuals with one affected arm and remained at 627% in those with one affected leg For statistical analysis, the amount of reduction after CLT in the group with bilateral affected legs was considered to be 100% During follow-up, the right leg was maintained at 9959% of the initial reduction and the left leg improved to 120% Patients who were compliant showed significant increases in lymphedema reduction, whereas noncompliant patients lost part of their initial reduction

Angiogenesis as a target for tumor treatment.

Abstract: Angiogenesis is a key step in tumor growth, invasion and metastasis. Thus, antiangiogenic therapy was postulated to be an attractive approach for antitumor treatment. Based on today’s knowledge, at least three strategies for inhibition of angiogenesis are feasible: (1) inhibition of release of angiogenic factors from tumor cells and/or neutralization of angiogenic molecules that have already been released; (2) inhibition of vascular endothelial cell proliferation and migration, and (3) inhibition of the synthesis and turnover of vessel basement membrane. To date, a number of antiangiogenic agents have been identified. In animal models, treatment with angiogenesis inhibitors has proven antitumor effects. Early clinical experience with angiogenic inhibitors indicates that optimal antiangiogenic therapy in the future is likely to be based on the long-term administration to cancer patients in adjunct to surgery, radiotherapy and conventional chemotherapy.

Preliminary guidelines for the treatment of distress

Abstract: 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 with etoposide and cisplatin (Platinol). This regimen resulted in a 39% response rate and high toxicity. Then we used the combination UFT (tegafur and uracil)/leucovorin/etoposide: UFT 390 mg/m2/day orally on days 1 to 14; leucovorin 500 mg/m2 i.v. day 1, and 15 mg/12 h orally on days 2 to 14; and etoposide 100 mg/m2 i.v. on day 1 and then 200 mg/m2/day orally on days 2 and 3. Forty-six patients received a median of five courses. Five patients (11%) achieved a complete response and 12 (26%) a partial response, for an overall response rate of 37%. The response rate was 50% in patients with an Eastern Cooperative Oncology Group performance status of 0 to 1. Grades 3 to 4 toxicities appeared as follow: 17% of patients had diarrhea, 11% had nausea/vomiting, and 13% of patients had anemia. One patient died of neutropenia and sepsis. The median survival time was 9 months. In summary, UFT/leucovorin/etoposide is effective and moderately toxic in patients with advanced gastric cancer. A new trial with UFT/leucovorin/epirubicin is ongoing.

Imagery and hypnosis in the treatment of cancer patients.

Abstract: Many patients with cancer often seek some means of connecting their mental activity with the unwelcome events occurring in their bodies, via techniques such as imagery and hypnosis. Hypnosis has been shown to be an effective method for controlling cancer pain. The techniques most often employed involve physical relaxation coupled with imagery that provides a substitute focus of attention for the painful sensation. Other related imagery techniques, such as guided imagery, involve attention to internally generated mental images without the formal use of hypnosis. The most well-known of these techniques involves the use of "positive mental images" of a strong army of white blood cells killing cancer cells. Despite claims to the contrary, no reliable evidence has shown that this technique affects disease progression or survival. Studies evaluating more broadly defined forms psychosocial support have come to conflicting conclusions about whether or not these interventions affect survival of cancer patients. However, 10-year follow-up of a randomized trial involving 86 women with cancer showed that a year of weekly "supportive/expressive" group therapy significantly increased survival duration and time from recurrence to death. This intervention encourages patients to express and deal with strong emotions and also focuses on clarifying doctor-patient communication. Numerous other studies suggest that suppression of negative affect, excessive conformity, severe stress, and lack of social support predict a poorer medical outcome from cancer. Thus, further investigation into the interaction between body and mind in coping with cancer is warranted. [ONCOLOGY 11(8):1179-1195, 1997]

Neuroblastoma: Biology and Therapy

Abstract: Neuroblastoma is the most common extracranial solid tumor of childhood, accounting for 15% of cancer-related deaths. These tumors have a predilection for young children; 60% of cases occur before age 2 years and 97% before age 10. Neuroblastomas derive from embryonic neural crest cells of the peripheral sympathetic nervous system. The behavior of this malignancy is characterized by marked clinical heterogeneity, ranging from spontaneous maturation in some patients to inexorable rapid metastatic progression in others. This article will discuss some of the molecular and biological features of neuroblastoma that are associated with these differences in behavior, and how these features have been used to develop a risk-based approach to therapy.

An Overview of Adenocarcinoma of the Small Intestine

Abstract: Even though the small intestine contains 90% of the gastrointestinal tract mucosa and is located between the stomach and large intestine, two organs with a high cancer incidence, adenocarcinoma of the small intestine is 1/50th as common as adenocarcinoma of the large bowel. In several other respects, small-intestinal adenocarcinoma resembles large bowel adenocarcinoma; eg, it arises from adenomatous polyps, co-occurs in the same individuals, and has a similar pattern of incidence rates by country. Small-intestinal adenocarcinoma is diagnosed prior to surgery in only about 50% of cases and often occurs in conjunction with small bowel obstruction. The mainstay of treatment is surgery; prognosis depends on stage at presentation. Little is known about the use of radiotherapy and chemotherapy in this malignancy, but most physicians utilize therapeutic strategies modeled on the management of large-intestinal adenocarcinoma. Clarification of the reason for the low incidence of small-intestinal adenocarcinoma could lead to new interventions for the prevention of colorectal cancer.

Tissue expression and serum levels of HER-2/neu in patients with breast cancer.

Abstract: We have analyzed serum levels of soluble HER-2/neu in 42 primary breast cancer patients prior to any therapy and studied the relationship between the overexpression and amplification of HER-2/neu in the primary tumor after surgical excision and data obtained by pathohistological staging. In addition, we have investigated the sera of 62 patients with stage IV breast cancer. Using an enzyme-linked immunosorbent assay, we observed elevated serum HER-2/neu levels in 6/42 (14.2%) preoperative patients. In 42.8% of the patients with HER-2/neu tumor expression/amplification serum levels were increased. In contrast, only 8.5% of the patients without HER-2/neu expression/amplification in the primary tumor presented with elevated serum levels. There was a significant correlation between serum concentrations of soluble HER-2/neu and tumor size (p < 0.0001) or axillary lymph node involvement (p < 0.0001). In patients with stage IV disease, 27 of 62 (43.5%) had elevated soluble HER-2/neu serum levels. A highly significant correlation between soluble HER-2/ neu and CA 15-3 (p < 0.002) was observed. The correlation of serum concentrations of HER-2/neu with estrogen and progesterone receptor status of the primary tumor was not significant in both groups. In conclusion, the measurement of serum HER-2/neu levels at diagnosis defines a small subgroup of breast cancer patients with a relatively advanced stage of disease. Its strong correlation with tumor load in patients with stage II disease and the high prevalence in patients with stage IV disease could make it a promising tool for the assessment of disease activity and biologic behavior in breast cancer.

Adrenocortical Carcinoma: Experience in 45 Patients

Abstract: Forty-five patients with adrenocortical carcinoma (13 nonfunctioning and 32 functioning carcinomas) were retrospectively studied. Five-year survival rate was 29% overall; for patients at stage I–II (n

Immunohistochemical Detection of bcl-2 and p53 Proteins and Apoptosis in Soft Tissue Sarcoma: Their Correlations with Prognosis

Abstract: Information on prognostic factors is essential to establish appropriate therapeutic modalities for soft tissue sarcoma (STS). To evaluate the biological nature and prognostic factors of STS, p53 and b

Apoptosis and Response to Radiation: Implications for Radiation Therapy

Abstract: Apoptosis is a mode of cell death that is currently of intense research interest in developmental and cancer biology. For more than 40 years, radiobiologists have been aware of cells in irradiated specimens that display the

Overexpression of metallothionein correlates with chemoresistance to cisplatin and prognosis in esophageal cancer

Abstract: The aim of this study was to determine the correlation of metallothionein (MT) expression with resistance to cisplatin and to identify prognostic factors in esophageal cancer. Immunostaining for MT was performed on the specimens of squamous cell carcinoma of the esophagus resected from 68 patients with curative intent. The expression of MT was evaluated in terms of clinicopathologic variables, effect of cisplatin, and the patients' survival. Overexpression of MT in the tumor was found in 70.6% of the patients. Stage III and IV tumors were more common in MT-positive tumors (p = 0.0282) but there was no difference in other clinicopathologic variables between MT-positive and MT-negative groups. Stage, cisplatin therapy, and tumor length were the independent prognostic indicators by multivariate analysis. Among 43 patients treated with cisplatin, the 5-year survival rate was 56% for MT-negative and 26% for MT-positive patients (p = 0.0277). In the MT-negative patients, multivariate analysis revealed that curability, stage, cisplatin therapy, and tumor length were the independent prognostic factors. These findings suggest that MT expression in squamous cell carcinoma of the esophagus is a major determinant of the chemoresistance to cisplatin and may be a predictor of poor prognosis.

Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implications.

Abstract: The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular inhibitor of these proteolytic enzymes, were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p < 0001) However no difference was observed between HCC and LC groups Interestingly, a significant relationship was evidenced between cathepsin B serum content and the grade of severity of cirrhosis (r = 041; p < 0001) Cathepsin L was significantly elevated only in sera of cancer patients as compared to normal subjects or LC patients (p < 0001) and significantly correlated with the number of malignant lesions (r = 049; p = 0001) Stefin A serum levels were increased in HCC and LC patients as compared to healthy subjects (p < 002) However, these levels were significantly higher in the LC group as compared to the HCC group (p < 005) In cancer patients, a significant relationship was observed between Stefin A serum content and tumor size (r = 035; p < 005), number of neoplastic lesions (r = 0556; p < 0001) and serum alpha-fetoprotein (r = 038; p < 001) These data suggest that cathepsin B and L and Stefin A may be potentially useful as additional biochemical parameters to monitor the therapeutic response of these diseases to clinical treatments and to identify patients with cirrhosis developing precancerous lesions

Prostate Cancer and African-American Men

Abstract: The article by Powell highlights uncertainties about the relative contributions of diagnostic delay and tumor biology to racial disparities in stage at diagnosis among American men with prostate cancer, and explores a variety of factors that may discourage early cancer detection in African-American men. Observations derived from our ongoing prospective studies of prostate cancer diagnosis and treatment outcomes in black and white American veterans and from our experience with prostate cancer screening at the University of Mississippi Hospital and Clinics afford additional insights into these issues and provide a framework for this commentary.

Management of Tumors of the Parapharyngeal Space

Abstract: Benign and malignant tumors can arise from any of the structures contained within the parapharyngeal space. Such tumors are very rare, however. Also, malignant tumors from adjacent areas (eg, the pharynx) can extend into the parapharyngeal space by direct growth, or distant tumors may metastasize to the lymphatics within the space. Although the history and physical examination can provide clues to the site of origin and nature of a parapharyngeal space tumor, imaging studies are more useful for defining the site of origin and extent of the mass, as well as its vascularity and relationship to the great vessels of the neck and other neurovascular structures. Surgery is the mainstay of treatment. The surgical approach chosen should facilitate complete tumor extirpation with minimal morbidity. Irradiation is administered as primary therapy in patients with unresectable tumors, poor surgical candidates, and selected other patients. Radiation therapy is also used after surgery for high-grade malignancies or when wide surgical margins cannot be achieved.

Docetaxel as neoadjuvant chemotherapy in patients with stage III breast cancer.

Abstract: Optimal management of locally advanced breast cancer (stage III) generally includes a combination of primary chemotherapy followed by surgery (if feasible), and local radiotherapy and adjuvant chemotherapy with or without hormonal therapy. An ongoing phase II study is being performed to evaluate the use of 4 cycles of 100 mg/m2 of docetaxel (Taxotere) administered as a 1-hour intravenous infusion once every 3 weeks followed by surgery, 4 cycles of standard-dose doxorubicin/cyclophosphamide (Cytoxan, Neosar) chemotherapy, and radiation, with and without tamoxifen (Nolvadex) in patients with locally advanced breast cancer. Preliminary results from 33 patients included in this phase II study are reported here. A partial response was achieved in 22 patients (67%), with 6 patients (18%) experiencing a complete response with this regimen. One patient with a complete response was confirmed to have a complete pathologic response at the time of surgery. Febrile neutropenia was noted in 8 patients (24%) and in 8 of the 120 treatment cycles (7%) administered. Future trials aimed at increasing the number of pathologic complete responses in patients with stage III breast cancer may require the use of docetaxel in combination with other active agents or the use of dose-dense scheduling schemes.

NSABP Protocol B-27. Preoperative doxorubicin plus cyclophosphamide followed by preoperative or postoperative docetaxel

Abstract: Protocol B-27, conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), is a phase III, randomized trial designed to evaluate whether sequencing docetaxel (Taxotere) to neoadjuvant doxorubicin/cyclophosphamide (Cytoxan, Neosar) prolongs disease-free and overall survival in patients with operable breast cancer. Patients are being randomized into three groups. The control group receives four 21-day courses of doxorubicin/cyclophosphamide chemotherapy with tamoxifen (Nolvadex), followed by breast surgery (and postoperative radiation for patients receiving breast-conserving surgery). Two experimental groups receive the same doxorubicin/cyclophosphamide chemotherapy and tamoxifen, followed by docetaxel--either before (preoperative group) or after (postoperative group) surgery. In the first 11 months of the study, 283 patients--of a projected 1,606 patients over a 5-year period--have been entered. Slightly more than half of the patients are younger than 50 years of age. Nearly half of the patients presented with tumors that were more than 4.0 cm in greatest diameter. Biopsy was performed by fine-needle aspiration slightly more than half of the time. Slightly more than two-thirds of the patients had clinically negative nodes. Lumpectomy was the proposed surgery at entry in 40% to 43% of the patients. As of November 1996, toxicity information is available on 29 patients in the preoperative docetaxel group and 23 patients in the postoperative docetaxel group. So far, there have been no unexpected toxicities, but the data are too preliminary to report in detail.

Management of progressive metastatic prostate cancer.

Abstract: Metastatic prostate cancer is a growing health problem and is the second leading cause of cancer death in men. While the response of patients with metastatic prostate cancer to initial hormonal manipulation is excellent, the majority of patients eventually progress. As a result, a growing number of patients and their physicians need-to-find acceptable therapeutic alternatives. Fortunately, the number of therapies in the management armamentarium is growing and includes: alternative hormonal therapies, chemotherapy, radioisotopes, and investigational agents. The major focus of treatment has shifted to palliation and quality of life. The decline of prostate-specific antigen (PSA) has become another important end point as evidence supporting a correlation with prolonged survival mounts. Enrolling eligible patients in clinical trials is critical to the development of new treatment strategies for this difficult disease.

Weekly 24-Hour Infusion of High-Dose 5-Fluorouracil and Leucovorin in the Treatment of Advanced Gastric Cancers

Abstract: Systemic chemotherapy for advanced gastric cancer is frequently associated with significant treatment-related toxicity, which is particularly severe in patients presenting with a poor general condition. A search for effective and low-toxic regimens for this group of patients is mandatory. A weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (HDFL) has previously been demonstrated to be an effective treatment for advanced colorectal cancer with minimal toxicity. In the past 3 years, this regimen has been tested at our institutes in patients with advanced gastric cancer, the general condition of whom had made the use of intensive combination chemotherapy impossible. The regimen consisted of a weekly 24-hour infusion of 2,600 mg/ m2 of 5-FU and 300 mg/m2 of leucovorin. From August 1992 to December 1995, 34 patients had been treated with this regimen for a total of 488 courses (average: 14.4 per patient). Hematological toxicity of this regimen was minimal, with grade 3 or 4 leukopenia developing in only 1 (2.9%) patient. Other nonhematological toxicities were also negligible except a reversible neurotoxicity which developed in 2 patients. Twenty-five patients were eligible for response analysis. One complete response, 11 partial responses, 5 stable diseases, and 8 progressive diseases were observed. The response rate was 48% (32-72%, 95% CI). The median overall survival (OS) of the whole group was 7 months (range: 1-18+). The median OS and time to progression of the responders were 8.5 months (range: 2-18) and 5 months (range: 2-10+), respectively. The palliative effect was satisfactory with the Karnofsky performance status of the responders improving from a median of 50% (range: 20-90%) to 70% (range: 50-100%). Our retrospective data suggested that HDFL is an effective and low-toxic palliative treatment even in patients with a very poor general condition. We advocated that this regimen should be further tested in ordinary patients with advanced gastric cancer.

Linking outcomes management to quality-of-life measurement.

Abstract: Health-care workers now accept quality of life (QOL) as an important outcome to evaluate in clinical research and as a useful measure of quality care. Indeed, current demand for QOL assessment in clinical practice has outpaced the availability of valid, streamlined, cost-effective methods for carrying out such assessment, although new tools are in the offing. This paper will highlight some of the major challenges facing outcomes management and outcomes research, with particular focus on the development of a QOL instrument to evaluate and manage anemia and fatigue in cancer patients--the Functional Assessment of Cancer Therapy-Anemia (FACT-An). The newest version of broader QOL assessment system, the Functional Assessment of Chronic Illness Therapy (FACIT), will also be described.

Prognostic Significance of the Expressions of Metallothionein, Glutathione-S-Transferase-π, and P-Glycoprotein in Curatively Resected Gastric Cancer

Abstract: Although experimental studies indicate that overexpression of metallothionein (MT), glutathione-S-transferase-π; (GST-π;), or P-glycoprotein (P-GP) is related to the drug resistance of cancer cells, t

Successful medical treatment of an epithelioid hemangioendothelioma of liver

Abstract: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver of unknown etiology. Although HEH is usually characterized by a low grade malignancy and a good long-term prognosis, its growth can be progressive and lead to hepatic failure, extrahepatic metastasis and death. Several different antineoplastic agents have been proposed for cases of nonresectable HEH. We report the case of a 45-year-old man with HEH successfully treated with intravenous infusion of Adriamycin.

Combined-Modality Therapy for Head and Neck Cancer

Abstract: Chemotherapy, when combined with radiotherapy and/or surgery in the treatment of patients with head and neck cancer, appears to be most efficacious if it is given concurrently with radiotherapy. Concurrent chemotherapy and radiotherapy has been shown to improve locoregional control and/or disease-free or overall survival in some randomized trials. However, acute mucositis is usually increased with simultaneous drug and radiation administration, especially when more than one drug is given concurrently with radiotherapy. The optimal drug or drug combinations for use in combined-modality therapy and the optimal drug and radiation dose schedules remain to be determined. Alternating radiotherapy and combination chemotherapy may also be beneficial and needs further evaluation. Induction chemotherapy followed by definitive radiotherapy in the chemotherapy responders is an alternative treatment option for patients with locally advanced, resectable squamous cell carcinoma of the larynx or hypopharynx who desire organ function preservation. Induction and/or adjuvant chemotherapy may also decrease or delay the appearance of distant metastasis. However, induction chemotherapy has not been shown to improve locoregional control or overall survival. Further clinical trials using novel drugs, innovative radiation and drug dose schedules, and other treatment modifiers are needed to improve the therapeutic ratio.