ONCOLOGY Vol 16 No 5 | Oncology

Irinotecan and Other Agents in Upper Gastrointestinal and Genitourinary Tumors

May 02, 2002

The 4th Investigators’ Workshop sponsored by The University of Texas M. D. Anderson Cancer Center was held on July 25-29, 2001, in Colorado Springs, Colorado. The purpose of these annual workshops has been to review the latest data on new agents, with a particular focus on the broadly used agent irinotecan (CPT-11, Camptosar).

Anastrozole Receives FDA Priority Review for Early Breast Cancer Indication

May 02, 2002

The US Food and Drug Administration (FDA) has granted a 6-month priority review status to the supplemental new drug application filed by the AstraZeneca corporation for the use of anastrozole (Arimidex) in the adjuvant treatment of early breast cancer in postmenopausal women.

Breakthrough Pain in Cancer Associated With Increased Medical Services and Costs

May 01, 2002

Investigators from Memphis found that cancer patients who experience breakthrough pain require additional medical services that result in higher medical costs than those incurred by cancer patients without breakthrough pain. The study, published in the February 2002 issue of the Journal of Pain, reported that patients with breakthrough pain (perhaps two-thirds of this population) require more frequent hospitalizations and doctor visits than cancer patients without breakthrough pain. Patients who suffered from breakthrough pain incurred costs of approximately $12,000 a year for medical services specific to their pain (hospitalizations, emergency room, and physician visits), whereas patients who did not have breakthrough pain (but still experienced pain) incurred costs of approximately $2,400 a year.

Risk Modeling Can Reduce Hospitalizations of Breast Cancer Patients

May 01, 2002

Investigators recently reported the results of a study suggesting the benefits of identifying subgroups of breast cancer patients at high risk for hospitalization due to febrile neutropenia. Once identified, granulocyte colony-stimulating factor (G-CSF, Neupogen) might be administered prophylactically to these patients to help decrease the incidence of the side effect. The data were presented at the 24th annual San Antonio Breast Cancer Symposium.

Mammography Debate Continues

May 01, 2002

The journal Lancet recently published an important analysis from six physicians at Weill Cornell Medical College (359:404-406, 2002), rebutting an article published in an earlier issue of Lancet (358:1340-1342, 2001) that cast doubt on the value of mammography in preventing death from breast cancer.

National Marrow Donor Program Publishes New Transplant Center Directory

May 01, 2002

The National Marrow Donor Program (NMDP) has published the 2001-2002 Transplant Center Access Directory-a free resource for all patients who are undergoing a blood stem cell transplant and do not have a matching donor in their family.

Size of Lung Tumor Does Not Always Reflect Cancer Severity

May 01, 2002

A fundamental assumption of lung cancer screening is that small tumors are less likely to have metastasized than large tumors. However, in a new study conducted at Duke Comprehensive Cancer Center, researchers showed that size does not necessarily indicate the severity of the cancer.

Irinotecan/Gemcitabine Shows Promising Survival Rate in Advanced Pancreatic Cancer Patients

May 01, 2002

The combination of irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) produced a 1-year survival rate of 27%, which is greater than that reported for gemcitabine alone in previous studies in patients with advanced pancreatic cancer (15% and 18% 1-year survival rates, respectively). These study results were published in a recent issue of the Journal of Clinical Oncology (20:1182-1191, 2002).

Trastuzumab Therapy Optimized by Oncoprotein Blood Test

May 01, 2002

New research presented at the 93rd annual meeting of the American Association for Cancer Research (AACR) suggests that monitoring with the serum HER2/neu oncoprotein test may help oncologists assess the effect of trastuzumab (Herceptin)-based therapy in patients with metastatic breast cancer.

Controversies in Early-Stage Hodgkin’s Disease

May 01, 2002

In their review of the history of the management of stage I/II Hodgkin’s disease, Drs. Ng and Mauch describe the results of various treatment protocols and outline the questions posed by ongoing European, Canadian, and American trials. In a broad sense, the questions posed by these trials will help clinicians understand the benefits and complications of these treatments. However, as clinically oriented as they are, the current studies have yet to answer some common problems faced by private practitioners-the clinicians who, in North America, manage most patients with Hodgkin’s disease.

The Sentinel Node in Colorectal Carcinoma

May 01, 2002

The authors are to be complimented on a thoughtful and complete review of the application of the sentinel node paradigm to colorectal cancer. This paradigm is inherently quite different for colorectal cancer because, except for the occasional demonstration of variant anatomy, the technique will not alter the extent of surgery as it has done in melanoma and breast cancer.

Targeted Therapy in Squamous Cell Cancers of the Head and Neck

May 01, 2002

The 5-year survival of patients with locally advanced squamous cell cancers of the head and neck is still less than 30%. Treatment of these cancers involves significant functional impairment, diminished quality of life, and considerable time and expense. Local recurrence and distant metastases are still fairly common, and the development of second primary cancers has a significant impact on survival in patients with initial early-stage disease. Despite the success of combination chemoradiation in locally advanced head and neck cancers, these facts stress the need for improved treatment of this disease.

AIDS Malignancies in the Era of Highly Active Antiretroviral Therapy

May 01, 2002

The article by Drs. Gates and Kaplan provides an excellent review of malignancies associated with human immunodeficiency virus (HIV)-1 disease and chronicles the epidemiologic changes seen during the past 5 years. The literature review is very thorough and well balanced.

AIDS Malignancies in the Era of Highly Active Antiretroviral Therapy

May 01, 2002

A dramatic spike in the incidence of Kaposi’s sarcoma (KS) in never-married men in New York and California in 1981 was one of the first indications of a new disease now known as acquired immunodeficiency syndrome (AIDS). We now appreciate a number of mechanisms by which human immunodeficiency virus (HIV) infection contributes to the pathogenesis of these tumors. The article by Drs. Gates and Kaplan provides an excellent review of changes in the epidemiology, presentation, and treatment of these tumors since the development of potent combination anti-HIV therapy.

Special Targets for the Treatment and Prevention of Cancer: Angiogenesis, VEGF, COX-2

May 01, 2002

Identification of targets in tumor cells vs normal cells (or at least a differential in their expression) is certainly a promising method for approaching the treatment and, indeed, the prevention of cancer. Presently, targeting of patient tumor cells has taken on even greater importance and interest with the discovery of the new agent imatinib mesylate (STI571, Gleevec), which is targeted to a kinase present in chronic myeloid leukemia (CML) cells (p210 BCR-ABL abnormal cells), which is required for CML cells to survive, but is not present in normal leucocytes.[1] The results with this agent targeted to the p210 BCR-ABL tyrosine kinase are indeed spectacular. The agent is of even greater interest in that it also works against some gastrointestinal stromal sarcomas with gain of function mutations in c-kit (CD117).[2] This activity of a targeted agent against a solid tumor increases the interest in targeted therapy to an even greater degree.

The Sentinel Node in Colorectal Carcinoma

May 01, 2002

The role of sentinel lymph node identification has been investigated over the past decade in a variety of malignancies. It has become part of standard care for melanoma. Its role in breast cancer is evolving, but with the completion of two large randomized clinical trials, it will probably be added to the surgical armamentarium for the management of most breast cancers. Studies have been proposed or are under way to evaluate sentinel node mapping in head and neck cancer, penile and vulvar cancer, and gastrointestinal cancers.

Controversies in Early-Stage Hodgkin’s Disease

May 01, 2002

Drs. Ng and Mauch do an excellent job of summarizing the current conventional wisdom regarding the management of patients with clinical early-stage Hodgkin’s disease, although their citation of some studies is selective. Today nearly all patients with Hodgkin’s disease receive combined-modality therapy-usually an abbreviated course of a chemotherapy regimen (often one that has not been shown to cure the disease when used alone) followed by 20 to 40 Gy of involved-field radiation therapy. This approach certainly hides a multitude of sins. If you don’t give chemotherapy well, you can still achieve good disease control with the radiation therapy. If you can’t design a radiation port that encompasses known sites of disease, you can still get by because the systemic chemotherapy will leave relatively little for the radiation therapy to do.

Oral Complications of Cancer Therapy

May 01, 2002

Drs. Sonis and Fey are to be commended for their timely and thorough article on the oral complications of cancer therapies. It has been our experience that these side effects are not being adequately addressed in the clinical setting. This is especially true the further one is removed from large cancer treatment centers in urban areas.

Irinotecan, Cisplatin, and Radiation in Esophageal Cancer

May 02, 2002

The limited effectiveness of currently available chemotherapy in the treatment of advanced esophageal cancer, and the poor survival achieved in locally advanced disease with combined chemoradiotherapy with or without surgery, have prompted the evaluation of new agents. Irinotecan (CPT-11, Camptosar) has promising single-agent activity in gastrointestinal cancers.

Irinotecan for the Treatment of Cervical Cancer

May 02, 2002

Topoisomerase inhibitors have been widely studied for the treatment of refractory or recurrent cervical cancer. Various schedules have been used, with response rates ranging from 13% to 20%. The combination of cisplatin and irinotecan (CPT-11, Camptosar) is being studied in cervical cancer.

Irinotecan in Epithelial Ovarian Cancer

May 02, 2002

Ovarian cancer, the second most common gynecologic malignancy, accounts for approximately 14,000 deaths annually in the United States. Disease relapse after primary treatment, which consists mainly of surgery followed by platinum-based therapy, occurs in more than 60% of ovarian cancer patients overall, and in more than 80% of those diagnosed initially with advanced-stage disease.

AIDS Malignancies in the Era of Highly Active Antiretroviral Therapy

May 01, 2002

The introduction of highly active antiretroviral therapy (HAART) has had a dramatic impact on the morbidity and mortality of individuals living with human immunodeficiency virus (HIV). In addition to contributing to dramatic

Current Application of Selective COX-2 Inhibitors in Cancer Prevention and Treatment

May 01, 2002

The multistep process of carcinogenesis, which can take many years, provides many opportunities for intervention to inhibit disease progression. Effective chemoprevention agents may reduce the risk of cancer by inhibiting the initiation stage of carcinoma through induction of apoptosis or DNA repair in cells harboring mutations, or they may act to prevent promotion of tumor growth. Similarly, chemoprevention may entail blocking cancer progression to an invasive phenotype.

The Emerging Role of Angiogenesis Inhibitors in Hematologic Malignancies

May 01, 2002

Angiogenesis is an important component of the pathogenesis of hematologic malignancies. A negative prognostic implication of increased angiogenesis has been established for acute and chronic myeloid and lymphocytic leukemias, myeloproliferative diseases, multiple myeloma, non-Hodgkin’s lymphoma (NHL), and hairy cell leukemia. An association between the return of increased marrow vascularity to normal levels and durability of response has been established in some of these diseases.

Irinotecan/Cisplatin in Advanced, Treated Gastric or Gastroesophageal Junction Carcinoma

May 02, 2002

We conducted a phase II study to assess the response rate and toxicity profile of the irinotecan (CPT-11, Camptosar) plus cisplatin combination administered weekly to patients with at least one previous chemotherapy for advanced adenocarcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach or gastroesophageal junction with adequate liver, kidney, and bone marrow functions were treated with 50 mg/m² of irinotecan plus 30 mg/m² of cisplatin, both administered intravenously 1 day a week for 4 consecutive weeks, followed by a 2-week recovery period.

Synopsis of Angiogenesis Inhibitors in Oncology

May 01, 2002

Angiogenesis is a dynamic process essential for primary tumor growth and metastases. New insights into the basic understanding of the biologic processes responsible for angiogenesis have led to the characterization of potential therapeutic targets. Several strategies for the development of antiangiogenic therapeutic modalities have been employed, including agents that (1) decrease the activity of specific angiogenic factors, (2) decrease the activity of endothelial survival factors, (3) increase the activity of naturally occurring antiangiogenic agents, or (4) indirectly downregulate angiogenic and survival factor activity.

Role of Genomics in Identifying New Targets for Cancer Therapy

May 01, 2002

The detailed map of the human genome can potentially transform future cancer therapy by merging genomics with pharmacology, thereby identifying which patients will benefit from specific therapeutic agents. Single-nucleotide polymorphisms (SNPs) provide a valuable tool for this pharmacogenetic approach to cancer therapy.

Combined-Modality Therapy for Rectal Cancer Using Irinotecan

May 02, 2002

Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease.

The Sentinel Node in Colorectal Carcinoma

May 01, 2002

One of the most important prognostic factors in colorectal cancer is the presence or absence of regional lymph node metastases. In many instances, micrometastatic disease may not be found on routine pathologic analysis using hematoxylin and eosin staining, but may be discovered only with immunohistochemical methods or polymerase chain reaction assay.

Future Directions in Adjuvant Therapy for Rectal Cancer

May 02, 2002

The US National Cancer Institute Gastrointestinal Intergroup has contributed to the development of chemotherapy and radiation regimens for the treatment of stage II and III rectal cancer. The first Intergroup trial demonstrated improvement in relapse-free and overall survival for patients who received protracted venous infusion fluorouracil (5-FU) with radiation compared to those treated with bolus 5-FU.

Irinotecan and Gemcitabine in Patients With Solid Tumors: Phase I Trial

May 02, 2002

Using a day 1 and 8, every-3-week schedule, our purpose was to determine the maximum tolerated dose of irinotecan (CPT-11, Camptosar) that can be administered immediately after gemcitabine (Gemzar) at a dose of 1,000 mg/m² IV. In this phase I trial, the maximum tolerated dose was defined as the dose level immediately below the level in which two of the first three patients in any cohort, or at least two of six patients in any expanded cohort, experienced dose-limiting toxicity. Dose-limiting toxicity pertained only to toxicity during the first cycle of treatment. Escalation of irinotecan was planned in groups of three patients, with three additional patients added at the first indication of dose-limiting toxicity. A total of 19 patients have been enrolled.

Potential Role of Selective COX-2 Inhibitors in Cancer Management

May 01, 2002

Tumorigenesis is a complex process, and understanding the mechanisms behind tumorigenesis is key to identifying effective targeted therapies. Prostaglandins are signaling lipophilic molecules derived from phospholipids that are involved in normal physiologic functions.

Preoperative Chemoradiation for Locally Advanced Rectal Cancer: Emerging Treatment Strategies

May 02, 2002

Over the past decade, patients with locally advanced rectal cancer at The University of Texas M. D. Anderson Cancer Center have been managed with preoperative chemoradiation. Patients achieving a complete clinical response to preoperative chemoradiation have had better pelvic tumor control, sphincter preservation, and overall survival than those with gross residual disease. Some patients achieving a complete clinical response have even had rectal-preserving surgery (full-thickness local excision).

Controversies in Early-Stage Hodgkin’s Disease

May 01, 2002

Early-stage Hodgkin’s disease accounts for approximately 60% of all cases of the illness. Because of its excellent cure rate (80% to 90%) and high salvage rate, it is difficult to demonstrate survival advantages for

Controversies in Early-Stage Hodgkin’s Disease

May 01, 2002

The optimal choice of treatment for early-stage Hodgkin’s disease depends on (1) knowledge of the prognostic factors that may influence treatment outcome and (2) the risk of acute and long-term complications incurred by treatment. For prognostic and therapeutic considerations, patients are divided into those with early-stage, favorable-prognosis disease (clinical stage I/II without risk factors) and those with early-stage, unfavorable-prognosis or intermediate-stage disease (clinical stage I/II with risk factors).

The Molecular Basis of Blood Diseases, 3rd Edition

May 01, 2002

This comprehensive text focuses on the pathophysiology of hematologic diseases. There is no field in which molecular techniques have been applied more fruitfully. Given the large amount of rapidly accumulating information in the field, this book fills a niche that will become increasingly important.

Oral Complications of Cancer Therapy

May 01, 2002

The mouth is a frequent site of complications arising from drug or radiation cancer therapy, with mucositis, xerostomia, osteoradionecrosis, and local infections being the most common. From the standpoint of dose

Commentary (Paulino): Current Management of Childhood Ependymoma

May 01, 2002

Dr. Merchant provides a comprehensive overview of intracranial ependymoma in children. As he points out, most of the current information regarding childhood intracranial ependymoma has come from single-institution retrospective reviews. Of the prognostic indicators mentioned in the article, both young age and subtotal resection are widely accepted. Children less than 3 years old have a worse prognosis than older children, possibly because of more aggressive tumor biology, reluctance to give postoperative radiotherapy, or use of lower doses of radiotherapy. Regarding the degree of surgical resection, assessment by postoperative imaging is more important than the neurosurgeon’s perspective on whether a gross total or subtotal resection has been performed.[1,2]

Commentary (Cohen/Glod): Current Management of Childhood Ependymoma

May 01, 2002

Ependymoma is a rare central nervous system (CNS) tumor in children, and our progress in treating this disease has been hampered by its rarity as well as by a nonuniform approach to treatment among practitioners. Dr. Merchant’s comprehensive review provides a framework for plotting a course of further progress in treating children with ependymoma.

Current Management of Childhood Ependymoma

May 01, 2002

Radiation therapy has long been a mainstay in the treatment of ependymoma. Concerns about the long-term effects of radiation therapy have made many parents and caregivers wary of this treatment modality. However, with the advent of conformal radiation and evidence

Early Breast and Ovarian Cancers Detected in Women at High Risk

May 01, 2002

When the BRCA1 and BRCA2 genes for breast and ovarian cancers were first identified and a screening blood test became available, a debate ensued as to whether there was an advantage to learning one’s risk. Recently, the value of such testing was demonstrated in a study in women who were followed after being identified as carriers of a BRCA genetic mutation. Researchers at Memorial Sloan-Kettering Cancer Center have provided strong evidence that breast and ovarian cancers can be detected at an early stage in women at highest hereditary risk. Results of the study were published in a recent issue of the Journal of Clinical Oncology (20:1260-1268, 2002).

Promising New Treatment Option for Primary Bone Cancer

May 12, 2002

A new study conducted by researchers at the Mayo Clinic shows that samarium-153 lexidronam (Quadramet), approved by the US Food and Drug Administration (FDA) in 1997 for the treatment of pain in patients with metastatic bone lesions, can be used at higher doses to treat osteosarcoma. The results of the study were published recently in the Journal of Clinical Oncology (20:189-196, 2002).